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Clinical Trial Results:
Efficacy, Safety, Tolerability and Pharmacokinetics of Tofacitinib for Treatment of Systemic Juvenile Idiopathic Arthritis (sJIA) With Active Systemic Features in Children and Adolescent Subjects

Summary
EudraCT number	2017-002018-29
Trial protocol	SK   PL   DE   BE   IT   NL   SE   HU
Global end of trial date	27 Mar 2024
Results information
Results version number	v1(current)
This version publication date	10 Oct 2024
First version publication date	10 Oct 2024
Other versions

Trial information Top of page
Trial identification
Sponsor protocol code	A3921165
Additional study identifiers
ISRCTN number	-
US NCT number	NCT03000439
WHO universal trial number (UTN)	-
Sponsors
Sponsor organisation name	Pfizer Inc.
Sponsor organisation address	235 E 42nd Street, New York, United States, NY 10017
Public contact	Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com
Scientific contact	Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com
Paediatric regulatory details
Is trial part of an agreed paediatric investigation plan (PIP)	Yes
EMA paediatric investigation plan number(s)	EMEA-000576-PIP01-09
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?	No
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?	Yes
Results analysis stage
Analysis stage	Final
Date of interim/final analysis	24 Jul 2024
Is this the analysis of the primary completion data?	No
Global end of trial reached?	Yes
Global end of trial date	27 Mar 2024
Was the trial ended prematurely?	No
General information about the trial
Main objective of the trial	To assess the sustained efficacy of tofacitinib versus placebo in sJIA participants, as measured by time to sJIA flare in the double-blind randomized withdrawal phase.
Protection of trial subjects	The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Council for Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trials subjects were followed.
Background therapy	-
Evidence for comparator	-
Actual start date of recruitment	10 May 2018
Long term follow-up planned	No
Independent data monitoring committee (IDMC) involvement?	Yes
Population of trial subjects
Number of subjects enrolled per country
Country: Number of subjects enrolled	Argentina: 2
Country: Number of subjects enrolled	Belgium: 1
Country: Number of subjects enrolled	Brazil: 3
Country: Number of subjects enrolled	Canada: 2
Country: Number of subjects enrolled	China: 26
Country: Number of subjects enrolled	Germany: 1
Country: Number of subjects enrolled	India: 22
Country: Number of subjects enrolled	Israel: 7
Country: Number of subjects enrolled	Italy: 1
Country: Number of subjects enrolled	Mexico: 4
Country: Number of subjects enrolled	Poland: 1
Country: Number of subjects enrolled	Russian Federation: 3
Country: Number of subjects enrolled	South Africa: 9
Country: Number of subjects enrolled	Spain: 4
Country: Number of subjects enrolled	Türkiye: 1
Country: Number of subjects enrolled	Ukraine: 7
Country: Number of subjects enrolled	United States: 6
Worldwide total number of subjects	100
EEA total number of subjects	8
Number of subjects enrolled per age group
In utero	0
Preterm newborn - gestational age < 37 wk	0
Newborns (0-27 days)	0
Infants and toddlers (28 days-23 months)	0
Children (2-11 years)	60
Adolescents (12-17 years)	40
Adults (18-64 years)	0
From 65 to 84 years	0
85 years and over	0

Trial information Top of page

Subject disposition Top of page
Recruitment
Recruitment details	Details participants who were diagnosed with Systemic Juvenile Idiopathic Arthritis (sJIA) with active systemic features were enrolled.
Pre-assignment
Screening details	A total of 168 participants were screened, of which 68 failed screening and only 100 participants were enrolled in open label part 1 (OLP1). From the total of 100 participants enrolled into OLP1 of the study, 54 participants were treated in open label part 2 (OLP2), and 59 participants were randomised between the treatment groups in the DB phase.
Period 1
Period 1 title	Overall Study (overall period)
Is this the baseline period?	Yes
Allocation method	Randomised - controlled
Blinding used	Double blind
Roles blinded	Investigator, Subject
Blinding implementation details	OL Part 1 and Part 2 was open label and allocation was not applicable
Arms
Are arms mutually exclusive	No
Arm title	Tofacitinib 5mg BID Open_Label (OL) Part 1
Arm description	Participants were administered tofacitinib 5 milligram (mg) twice a day (BID) via the oral route and continued to receive a stable dose of corticosteroids (Cs) during open label part 1.
Arm type	Experimental
Investigational medicinal product name	Tofacitinib
Investigational medicinal product code
Other name
Pharmaceutical forms	Oral solution, Tablet
Routes of administration	Oral use
Dosage and administration details	Tofacitinib 5 mg was administered as an oral tablet BID for participants greater than equal to (>=) 40 kilograms (kg) and as an equivalent weight-based lower dose of tofacitinib oral solution (1 mg/mL) BID for participants less than (<) 40 kg.
Arm title	Tofacitinib 5mg BID OL Part 2
Arm description	Participants who achieved sJIA American college of rheumatology (ACR) 50 response and maintained sJIA ACR 30 response for 4 weeks were administered tofacitinib 5 mg BID and tapering dose of CSs for participants treated with ˃0.2 milligram/kilogram/day (mg/kg/day) oral prednisone (or equivalent).
Arm type	Experimental
Investigational medicinal product name	Tofacitinib
Investigational medicinal product code
Other name
Pharmaceutical forms	Tablet, Oral solution
Routes of administration	Oral use
Dosage and administration details	Tofacitinib 5 mg was administered as an oral tablet BID for participants >=40 kg and as an equivalent weight-based lower dose of tofacitinib oral solution (1 mg/mL) BID for participants <40 kg.
Arm title	Tofacitinib 5mg BID Double-Blind (DB)
Arm description	Participants who maintained a stable tapered CS dose for 4 weeks and maintained sJIA ACR 30 for 4 weeks from Part 1 and Part 2 of the open-label phase continued to receive tofacitinib 5 mg BID orally during the double-blind withdrawal phase of the study.
Arm type	Experimental
Investigational medicinal product name	Tofacitinib
Investigational medicinal product code
Other name
Pharmaceutical forms	Tablet, Oral solution
Routes of administration	Oral use
Dosage and administration details	Tofacitinib 5 mg was administered as an oral tablet BID for participants >=40 kg and as an equivalent weight-based lower dose of tofacitinib oral solution (1 mg/mL) BID for participants <40 kg.
Arm title	Placebo DB
Arm description	Participants who maintained a stable tapered CS dose for 4 weeks and maintained sJIA ACR 30 for 4 weeks from Part 1 and Part 2 of the open-label phase were randomised to receive placebo BID orally during the double-blind withdrawal phase of the study.
Arm type	Placebo
Investigational medicinal product name	Placebo
Investigational medicinal product code
Other name
Pharmaceutical forms	Tablet, Oral solution
Routes of administration	Oral use
Dosage and administration details	Placebo of tofacitinib 5 mg was administered as an oral tablet BID for participants >=40 kg and as an equivalent weight-based lower dose of tofacitinib oral solution (1 mg/mL) BID for participants <40 kg.
Number of subjects in period 1 Tofacitinib 5mg BID Open_Label (OL) Part 1 Tofacitinib 5mg BID OL Part 2 Tofacitinib 5mg BID Double-Blind (DB) Placebo DB Started 100 54 28 31 Completed 76 37 14 17 Not completed 24 17 14 14      Adverse event, non-fatal 2 - 2 -      Adverse event, serious non-fatal 4 - - 1      Unspecified 2 5 10 11      Withdrawal by parent/guardian - - 2 -      Insufficient clinical response 16 12 - 2

Subject disposition Top of page

Baseline characteristics Top of page
Baseline characteristics reporting groups
Reporting group title	Tofacitinib 5mg BID Open_Label (OL) Part 1
Reporting group description	Participants were administered tofacitinib 5 milligram (mg) twice a day (BID) via the oral route and continued to receive a stable dose of corticosteroids (Cs) during open label part 1.
Reporting group title	Tofacitinib 5mg BID OL Part 2
Reporting group description	Participants who achieved sJIA American college of rheumatology (ACR) 50 response and maintained sJIA ACR 30 response for 4 weeks were administered tofacitinib 5 mg BID and tapering dose of CSs for participants treated with ˃0.2 milligram/kilogram/day (mg/kg/day) oral prednisone (or equivalent).
Reporting group title	Tofacitinib 5mg BID Double-Blind (DB)
Reporting group description	Participants who maintained a stable tapered CS dose for 4 weeks and maintained sJIA ACR 30 for 4 weeks from Part 1 and Part 2 of the open-label phase continued to receive tofacitinib 5 mg BID orally during the double-blind withdrawal phase of the study.
Reporting group title	Placebo DB
Reporting group description	Participants who maintained a stable tapered CS dose for 4 weeks and maintained sJIA ACR 30 for 4 weeks from Part 1 and Part 2 of the open-label phase were randomised to receive placebo BID orally during the double-blind withdrawal phase of the study.
Reporting group values Tofacitinib 5mg BID Open_Label (OL) Part 1 Tofacitinib 5mg BID OL Part 2 Tofacitinib 5mg BID Double-Blind (DB) Placebo DB Total Number of subjects 100 54 28 31 213 Age Categorical A total of 100 participants were enrolled into the study. From the total of 100 participants enrolled into the OL part 1 of the study. 54 participants entered in OL part 2. From OL phase, 59 participants were randomised between the treatment group in the DB phase. The number of participants in total column are not presenting actual enrolled participants. Units: Participants     2 to < 6 Years 17 10 3 6 36     6 to < 12 Years 43 21 12 11 87     12 to < 18 Years 40 23 13 14 90 Age continuous Units: years     arithmetic mean (standard deviation) 9.97 ( 4.11 ) 9.85 ( 4.33 ) 10.36 ( 4.34 ) 10.35 ( 4.55 ) - Gender categorical A total of 100 participants were enrolled into the study. From the total of 100 participants enrolled into the OL part 1 of the study. 54 participants entered in OL part 2. From OL phase, 59 participants were randomised between the treatment group in the DB phase. The number of participants in total column are not presenting actual enrolled participants. Units: Participants     Male 56 33 16 22 127     Female 44 21 12 9 86 Ethnicity A total of 100 participants were enrolled into the study. From the total of 100 participants enrolled into the OL part 1 of the study. 54 participants entered in OL part 2. From OL phase, 59 participants were randomised between the treatment group in the DB phase. The number of participants in total column are not presenting actual enrolled participants. Units: Subjects     Hispanic or Latino 14 11 3 4 32     Not Hispanic or Latino 86 43 25 27 181 Race A total of 100 participants were enrolled into the study. From the total of 100 participants enrolled into the OL part 1 of the study. 54 participants entered in OL part 2. From OL phase, 59 participants were randomised between the treatment group in the DB phase. The number of participants in total column are not presenting actual enrolled participants. Units: Subjects     White 39 23 11 13 86     Black or African American 7 4 3 2 16     Asian 49 23 13 14 99     Other 5 4 1 2 12

Baseline characteristics Top of page

End points Top of page
End points reporting groups
Reporting group title	Tofacitinib 5mg BID Open_Label (OL) Part 1
Reporting group description	Participants were administered tofacitinib 5 milligram (mg) twice a day (BID) via the oral route and continued to receive a stable dose of corticosteroids (Cs) during open label part 1.
Reporting group title	Tofacitinib 5mg BID OL Part 2
Reporting group description	Participants who achieved sJIA American college of rheumatology (ACR) 50 response and maintained sJIA ACR 30 response for 4 weeks were administered tofacitinib 5 mg BID and tapering dose of CSs for participants treated with ˃0.2 milligram/kilogram/day (mg/kg/day) oral prednisone (or equivalent).
Reporting group title	Tofacitinib 5mg BID Double-Blind (DB)
Reporting group description	Participants who maintained a stable tapered CS dose for 4 weeks and maintained sJIA ACR 30 for 4 weeks from Part 1 and Part 2 of the open-label phase continued to receive tofacitinib 5 mg BID orally during the double-blind withdrawal phase of the study.
Reporting group title	Placebo DB
Reporting group description	Participants who maintained a stable tapered CS dose for 4 weeks and maintained sJIA ACR 30 for 4 weeks from Part 1 and Part 2 of the open-label phase were randomised to receive placebo BID orally during the double-blind withdrawal phase of the study.

End points Top of page

Primary: Time to Systemic Juvenile Idiopathic Arthritis (sJIA) Disease Flare: Double-Blind Phase Top of page
End point title	Time to Systemic Juvenile Idiopathic Arthritis (sJIA) Disease Flare: Double-Blind Phase [1]
End point description	Time to the disease flare=the number of days from randomisation to flare in the DB phase and calculated as date of disease flare=date of randomization plus (+)1. sJIA Flare=as at least one of the following criteria:Recurrence of fever (>38 degree Celsius/100.4-degree Fahrenheit) on 2 or more consecutive days) was considered due to SJIA activity.Worsening of 30 percent (%) or more in three or more of the six variables included: Number of joints with active arthritis and limited range of motion, disease activity, Parent child evaluation of overall well-being,functional ability (Disability Index), erythrocyte sedimentation rate (ESR), of the JIA core set with no more than one variable of the JIA core set improving by 30% compared to the day of randomisation into the withdrawal phase. 95% Confidence Interval (CI) based on Brookmeyer and Crowley Method. Double-Blind Full Analysis Set was used. 99999 indicates data could not be calculated due to less number of participants with events.
End point type	Primary
End point timeframe	From randomization to up to 248 weeks
Notes [1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint is specific to Double-Blind period hence Double-Blind arms have been reported.
End point values Tofacitinib 5mg BID Double-Blind (DB) Placebo DB Number of subjects analysed 28 31 Units: Days     median (confidence interval 95%) 99999 (186.0 to 99999) 295.0 (99.0 to 99999)
Statistical analysis title	Tofacitinib 5mg BID DB, Placebo DB
Statistical analysis description	Hazard ratio and 95% CI was based on Cox proportional hazards model with treatment group as covariate.
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type
P-value	= 0.1171
Method	Unstratified log-rank test
Parameter type	Hazard ratio (HR)
Point estimate	0.633
Confidence interval
level	95%
sides	2-sided
lower limit	0.296
upper limit	1.354

Primary: Time to Systemic Juvenile Idiopathic Arthritis (sJIA) Disease Flare: Double-Blind Phase Top of page

Secondary: Probability of Occurrence of sJIA Disease Flare at DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52: Double-Blind Phase Top of page
End point title	Probability of Occurrence of sJIA Disease Flare at DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52: Double-Blind Phase [2]
End point description	sJIA Flare was defined as at least one of the following criteria: recurrence of fever (>38° C/100.4° F) on 2 or more consecutive days) was considered due to SJIA activity. Worsening of 30% or more in three or more of the six variables: number of joints with active arthritis and limited range of motion, disease activity, parent child evaluation of overall well-being, functional ability (CHAQ Disability Index), ESR. of the JIA core set with no more than one variable of the JIA core set improving by 30% compared to the day of randomisation into the withdrawal phase. DBFAS consisted of all randomised participants who received at least one dose of investigational product in the double-blind phase.
End point type	Secondary
End point timeframe	DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Notes [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint is specific to Double-Blind period hence Double-Blind arms have been reported.
End point values Tofacitinib 5mg BID Double-Blind (DB) Placebo DB Number of subjects analysed 28 31 Units: Probability of event number (not applicable)     DB Week 4 7.1 6.5     DB Week 8 14.3 22.6     DB Week 12 21.4 32.3     DB Week 16 25.0 38.7     DB Week 20 32.1 45.4     DB Week 24 32.1 45.4     DB Week 28 35.9 45.4     DB Week 32 35.9 49.9     DB Week 36 40.5 49.9     DB Week 40 40.5 49.9     DB Week 44 40.5 55.5     DB Week 48 40.5 55.5     DB Week 52 40.5 55.5
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 4
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[3]
Method
Parameter type	Difference in percentage
Point estimate	0.7
Confidence interval
level	95%
sides	2-sided
lower limit	-12.2
upper limit	13.6
Notes [3] - The 95% CIs for the differences between the treatment groups were generated using Greenwood’s formula.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 12
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[4]
Method
Parameter type	Difference in percentage
Point estimate	-10.8
Confidence interval
level	95%
sides	2-sided
lower limit	-33.2
upper limit	11.6
Notes [4] - The 95% CIs for the differences between the treatment groups were generated using Greenwood’s formula.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 16
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[5]
Method
Parameter type	Difference in percentage
Point estimate	-13.7
Confidence interval
level	95%
sides	2-sided
lower limit	-37.2
upper limit	9.8
Notes [5] - The 95% CIs for the differences between the treatment groups were generated using Greenwood’s formula.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 20
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[6]
Method
Parameter type	Difference in percentage
Point estimate	-13.2
Confidence interval
level	95%
sides	2-sided
lower limit	-37.9
upper limit	11.5
Notes [6] - The 95% CIs for the differences between the treatment groups were generated using Greenwood’s formula.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 24
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[7]
Method
Parameter type	Difference in percentage
Point estimate	-13.2
Confidence interval
level	95%
sides	2-sided
lower limit	-37.9
upper limit	11.5
Notes [7] - The 95% CIs for the differences between the treatment groups were generated using Greenwood’s formula.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 8
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[8]
Method
Parameter type	Difference in percentage
Point estimate	-8.3
Confidence interval
level	95%
sides	2-sided
lower limit	-27.9
upper limit	11.3
Notes [8] - The 95% CIs for the differences between the treatment groups were generated using Greenwood’s formula.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 28
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[9]
Method
Parameter type	Difference in percentage
Point estimate	-9.4
Confidence interval
level	95%
sides	2-sided
lower limit	-34.5
upper limit	15.6
Notes [9] - The 95% CIs for the differences between the treatment groups were generated using Greenwood’s formula.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 44
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[10]
Method
Parameter type	Difference in percentage
Point estimate	-15
Confidence interval
level	95%
sides	2-sided
lower limit	-41.8
upper limit	11.8
Notes [10] - The 95% CIs for the differences between the treatment groups were generated using Greenwood’s formula.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 32
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[11]
Method
Parameter type	Difference in percentage
Point estimate	-14
Confidence interval
level	95%
sides	2-sided
lower limit	-39.5
upper limit	11.5
Notes [11] - The 95% CIs for the differences between the treatment groups were generated using Greenwood’s formula.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 36
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[12]
Method
Parameter type	Difference in percentage
Point estimate	-9.4
Confidence interval
level	95%
sides	2-sided
lower limit	-35.5
upper limit	16.7
Notes [12] - The 95% CIs for the differences between the treatment groups were generated using Greenwood’s formula.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 40
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[13]
Method
Parameter type	Difference in percentage
Point estimate	-9.4
Confidence interval
level	95%
sides	2-sided
lower limit	-35.5
upper limit	16.7
Notes [13] - The 95% CIs for the differences between the treatment groups were generated using Greenwood’s formula.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 48
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[14]
Method
Parameter type	Difference in percentage
Point estimate	-15
Confidence interval
level	95%
sides	2-sided
lower limit	-41.8
upper limit	11.8
Notes [14] - The 95% CIs for the differences between the treatment groups were generated using Greenwood’s formula.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 52
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[15]
Method
Parameter type	Difference in percentage
Point estimate	-15
Confidence interval
level	95%
sides	2-sided
lower limit	-41.8
upper limit	11.8
Notes [15] - The 95% CIs for the differences between the treatment groups were generated using Greenwood’s formula.

Secondary: Probability of Occurrence of sJIA Disease Flare at DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52: Double-Blind Phase Top of page

Secondary: Percentage of Participants who Achieved Successful Corticosteroid Tapering: at the End of Open-label Phase Part 2 Top of page
End point title	Percentage of Participants who Achieved Successful Corticosteroid Tapering: at the End of Open-label Phase Part 2 [16]
End point description	A successfully tapered participant was considered as the one that completed part 2 of the OL by reaching their target corticosteroid dose and maintained an adapted JIA American College of Rheumatology (ACR) 30 response for four weeks on this dose. The target CS dose at the end of part 2 included <=0.5 mg/kg/day up to a maximum dose of 15 mg/day oral prednisone (or equivalent) for CS˃0.8 mg/kg/day oral prednisone; reduction to <=0.3 mg/kg/day up to a maximum of 12 mg/day oral prednisone (or equivalent) for CS <=0.8 mg/kg/day->=0.5 mg/kg/day oral prednisone (or equivalent) and <=0.2 mg/kg/day up to a maximum dose of 10 mg/day oral prednisone (or equivalent) for CS <0.5 mg/kg/day-CS˃0.2 mg/kg/day oral prednisone (or equivalent). 95% CI was based on normal approximation. Open-label part 2 analysis set included all participants who were enrolled into the open-label part 2 phase of the study and received at least one dose of investigational product in part 2.
End point type	Secondary
End point timeframe	From end of OL Part 1 to up to 24 weeks in OL Part 2
Notes [16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint is specific to Open-Label period hence Open-Label arms have been reported.
End point values Tofacitinib 5mg BID OL Part 2 Number of subjects analysed 54 Units: Percentage of participants     number (confidence interval 95%) 70.37 (58.19 to 82.55)
No statistical analyses for this end point

Secondary: Percentage of Participants who Achieved Successful Corticosteroid Tapering: at the End of Open-label Phase Part 2 Top of page

Secondary: Percentage of Participants who Achieved Corticosteroid Dose of Less Than or Equal to (<=) 0.2 mg/kg/day or 10 mg/day: at the End of Open-label Phase Part 2 Top of page
End point title	Percentage of Participants who Achieved Corticosteroid Dose of Less Than or Equal to (<=) 0.2 mg/kg/day or 10 mg/day: at the End of Open-label Phase Part 2 [17]
End point description	95% CI was based on normal approximation. OLPT2 analysis set included all participants who were enrolled into the open-label part 2 phase of the study and received at least one dose of investigational product in part 2.
End point type	Secondary
End point timeframe	From end of OL Part 1 to up to 24 weeks in OL Part 2
Notes [17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint is specific to Open-Label period hence Open-Label arms have been reported.
End point values Tofacitinib 5mg BID OL Part 2 Number of subjects analysed 54 Units: Percentage of participants     number (confidence interval 95%) 59.26 (46.15 to 72.36)
No statistical analyses for this end point

Secondary: Percentage of Participants who Achieved Corticosteroid Dose of Less Than or Equal to (<=) 0.2 mg/kg/day or 10 mg/day: at the End of Open-label Phase Part 2 Top of page

Secondary: Percentage of Participants with Adapted JIA ACR 30/50/70/90/100 Response at DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52: Double-Blind Phase Top of page
End point title	Percentage of Participants with Adapted JIA ACR 30/50/70/90/100 Response at DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52: Double-Blind Phase [18]
End point description	Adapted JIA ACR 30,50,70,90,100 response=absence of fever due to sJIA in preceding 7 days along with improvement of >=30,50,70,90,100%, respectively in at least 3 out of 6 JIA core set variables with no more than 1 JIA core set variable worsening by >=30%. Variables included: number of joints with active arthritis (any joint with swelling, or in absence of swelling, limitation of motion accompanied by either pain on motion or tenderness);number of joints with limited range of motion; physician global evaluation of disease activity on a visual analog scale (VAS) from 0=no disease activity to 100=very severe disease activity; Parent/ legal guardian/Child evaluation of overall well-being on VAS from 0= very well to 100 millimeter (mm)= very poor; functional ability (Disability Index) ESR. DBFAS set was used. Missing response was imputed as non-response.
End point type	Secondary
End point timeframe	DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Notes [18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint is specific to Double-Blind period hence Double-Blind arms have been reported.
End point values Tofacitinib 5mg BID Double-Blind (DB) Placebo DB Number of subjects analysed 28 31 Units: Percentage of participants number (not applicable)     ACR30:DB Week 4 82.14 93.55     ACR30:DB Week 8 82.14 80.65     ACR30:DB Week 12 71.43 70.97     ACR30:DB Week 16 71.43 61.29     ACR30:DB Week 20 67.86 51.61     ACR30:DB Week 24 64.29 54.84     ACR30:DB Week 28 60.71 51.61     ACR30:DB Week 32 60.71 51.61     ACR30:DB Week 36 60.71 51.61     ACR30:DB Week 40 60.71 51.61     ACR30:DB Week 44 60.71 51.61     ACR30:DB Week 48 60.71 48.39     ACR30:DB Week 52 60.71 48.39     ACR50:DB Week 4 82.14 93.55     ACR50:DB Week 8 82.14 77.42     ACR50:DB Week 12 71.43 70.97     ACR50:DB Week 16 71.43 58.06     ACR50:DB Week 20 67.86 48.39     ACR50:DB Week 24 64.29 54.84     ACR50:DB Week 28 60.71 51.61     ACR50:DB Week 32 60.71 51.61     ACR50:DB Week 36 60.71 51.61     ACR50:DB Week 40 60.71 51.61     ACR50:DB Week 44 60.71 48.39     ACR50:DB Week 48 60.71 48.39     ACR50:DB Week 52 60.71 48.39     ACR70:DB Week 4 57.14 70.97     ACR70:DB Week 8 67.86 77.42     ACR70:DB Week 12 64.29 64.52     ACR70:DB Week 16 60.71 54.84     ACR70:DB Week 20 64.29 45.16     ACR70:DB Week 24 53.57 51.61     ACR70:DB Week 28 57.14 41.94     ACR70:DB Week 32 60.71 48.39     ACR70:DB Week 36 60.71 51.61     ACR70:DB Week 40 60.71 48.39     ACR70:DB Week 44 60.71 48.39     ACR70:DB Week 48 60.71 48.39     ACR70:DB Week 52 60.71 48.39     ACR90:DB Week 4 28.57 48.39     ACR90:DB Week 8 21.43 38.71     ACR90:DB Week 12 25.00 38.71     ACR90:DB Week 16 25.00 29.03     ACR90:DB Week 20 21.43 29.03     ACR90:DB Week 24 21.43 25.81     ACR90:DB Week 28 17.86 25.81     ACR90:DB Week 32 14.29 29.03     ACR90:DB Week 36 28.57 35.48     ACR90:DB Week 40 28.57 32.26     ACR90:DB Week 44 28.57 29.03     ACR90:DB Week 48 28.57 29.03     ACR90:DB Week 52 28.57 29.03     ACR100:DB Week 4 14.29 35.48     ACR100:DB Week 8 10.71 29.03     ACR100:DB Week 12 14.29 25.81     ACR100:DB Week 16 17.86 25.81     ACR100:DB Week 20 14.29 12.90     ACR100:DB Week 24 17.86 19.35     ACR100:DB Week 28 14.29 22.58     ACR100:DB Week 32 10.71 25.81     ACR100:DB Week 36 14.29 25.81     ACR100:DB Week 40 21.43 29.03     ACR100:DB Week 44 21.43 25.81     ACR100:DB Week 48 25.00 25.81     ACR100:DB Week 52 25.00 25.81
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	ACR30: DB Week 4
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[19]
Method
Parameter type	Difference in percentage
Point estimate	-11.41
Confidence interval
level	95%
sides	2-sided
lower limit	-28.02
upper limit	5.21
Notes [19] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	ACR30: DB Week 8
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[20]
Method
Parameter type	Difference in percentage
Point estimate	1.5
Confidence interval
level	95%
sides	2-sided
lower limit	-18.37
upper limit	21.36
Notes [20] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	ACR30: DB Week 52
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[21]
Method
Parameter type	Difference in percentage
Point estimate	12.33
Confidence interval
level	95%
sides	2-sided
lower limit	-12.91
upper limit	37.56
Notes [21] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	ACR30: DB Week 48
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[22]
Method
Parameter type	Difference in percentage
Point estimate	12.33
Confidence interval
level	95%
sides	2-sided
lower limit	-12.91
upper limit	37.56
Notes [22] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	ACR30: DB Week 40
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[23]
Method
Parameter type	Difference in percentage
Point estimate	9.1
Confidence interval
level	95%
sides	2-sided
lower limit	-16.13
upper limit	34.33
Notes [23] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	ACR30: DB week 36
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[24]
Method
Parameter type	Difference in percentage
Point estimate	9.1
Confidence interval
level	95%
sides	2-sided
lower limit	-16.13
upper limit	34.33
Notes [24] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	ACR30: DB Week 32
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[25]
Method
Parameter type	Difference in percentage
Point estimate	9.1
Confidence interval
level	95%
sides	2-sided
lower limit	-16.13
upper limit	34.33
Notes [25] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	ACR30: DB Week 28
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[26]
Method
Parameter type	Difference in percentage
Point estimate	9.1
Confidence interval
level	95%
sides	2-sided
lower limit	-16.13
upper limit	34.33
Notes [26] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	ACR30: DB Week 24
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[27]
Method
Parameter type	Difference in percentage
Point estimate	9.45
Confidence interval
level	95%
sides	2-sided
lower limit	-15.49
upper limit	34.39
Notes [27] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	ACR30: DB Week 20
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[28]
Method
Parameter type	Difference in percentage
Point estimate	16.24
Confidence interval
level	95%
sides	2-sided
lower limit	-8.43
upper limit	40.92
Notes [28] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	ACR30: DB Week 16
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[29]
Method
Parameter type	Difference in percentage
Point estimate	10.14
Confidence interval
level	95%
sides	2-sided
lower limit	-13.82
upper limit	34.1
Notes [29] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	ACR30: DB Week 12
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[30]
Method
Parameter type	Difference in percentage
Point estimate	0.46
Confidence interval
level	95%
sides	2-sided
lower limit	-22.68
upper limit	23.6
Notes [30] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	ACR50: DB Week 40
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[31]
Method
Parameter type	Difference in percentage
Point estimate	9.1
Confidence interval
level	95%
sides	2-sided
lower limit	-16.13
upper limit	34.33
Notes [31] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	ACR50: DB Week 36
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[32]
Method
Parameter type	Difference in percentage
Point estimate	9.1
Confidence interval
level	95%
sides	2-sided
lower limit	-16.13
upper limit	34.33
Notes [32] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	ACR50: DB Week 32
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[33]
Method
Parameter type	Difference in percentage
Point estimate	9.1
Confidence interval
level	95%
sides	2-sided
lower limit	-16.13
upper limit	34.33
Notes [33] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	ACR50: DB Week 28
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[34]
Method
Parameter type	Difference in percentage
Point estimate	9.1
Confidence interval
level	95%
sides	2-sided
lower limit	-16.13
upper limit	34.33
Notes [34] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	ACR50: DB Week 24
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[35]
Method
Parameter type	Difference in percentage
Point estimate	9.45
Confidence interval
level	95%
sides	2-sided
lower limit	-15.49
upper limit	34.39
Notes [35] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	ACR50: DB Week 44
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[36]
Method
Parameter type	Difference in percentage
Point estimate	12.33
Confidence interval
level	95%
sides	2-sided
lower limit	-12.91
upper limit	37.56
Notes [36] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	ACR50: DB Week 16
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[37]
Method
Parameter type	Difference in percentage
Point estimate	13.36
Confidence interval
level	95%
sides	2-sided
lower limit	-10.76
upper limit	37.48
Notes [37] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	ACR50: DB Week 12
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[38]
Method
Parameter type	Difference in percentage
Point estimate	0.46
Confidence interval
level	95%
sides	2-sided
lower limit	-22.68
upper limit	23.6
Notes [38] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	ACR50: DB Week 8
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[39]
Method
Parameter type	Difference in percentage
Point estimate	4.72
Confidence interval
level	95%
sides	2-sided
lower limit	-15.72
upper limit	25.17
Notes [39] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	ACR50: DB Week 4
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[40]
Method
Parameter type	Difference in percentage
Point estimate	-11.41
Confidence interval
level	95%
sides	2-sided
lower limit	-28.02
upper limit	5.21
Notes [40] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	ACR50: DB Week 20
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[41]
Method
Parameter type	Difference in percentage
Point estimate	19.47
Confidence interval
level	95%
sides	2-sided
lower limit	-5.2
upper limit	44.14
Notes [41] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	ACR50: DB Week 48
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[42]
Method
Parameter type	Difference in percentage
Point estimate	12.33
Confidence interval
level	95%
sides	2-sided
lower limit	-12.91
upper limit	37.56
Notes [42] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	ACR50: DB Week 52
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[43]
Method
Parameter type	Difference in percentage
Point estimate	12.33
Confidence interval
level	95%
sides	2-sided
lower limit	-12.91
upper limit	37.56
Notes [43] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	ACR70: DB Week 4
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[44]
Method
Parameter type	Difference in percentage
Point estimate	-13.82
Confidence interval
level	95%
sides	2-sided
lower limit	-38.14
upper limit	10.49
Notes [44] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	ACR70: DB Week 8
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[45]
Method
Parameter type	Difference in percentage
Point estimate	-9.56
Confidence interval
level	95%
sides	2-sided
lower limit	-32.28
upper limit	13.15
Notes [45] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	ACR70: DB Week 12
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[46]
Method
Parameter type	Difference in percentage
Point estimate	-0.23
Confidence interval
level	95%
sides	2-sided
lower limit	-24.7
upper limit	24.24
Notes [46] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	ACR70: DB Week 16
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[47]
Method
Parameter type	Difference in percentage
Point estimate	5.88
Confidence interval
level	95%
sides	2-sided
lower limit	-19.31
upper limit	31.06
Notes [47] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	ACR70: DB Week 20
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[48]
Method
Parameter type	Difference in percentage
Point estimate	19.12
Confidence interval
level	95%
sides	2-sided
lower limit	-5.81
upper limit	44.06
Notes [48] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	ACR70: DB Week 24
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[49]
Method
Parameter type	Difference in percentage
Point estimate	1.96
Confidence interval
level	95%
sides	2-sided
lower limit	-23.55
upper limit	27.47
Notes [49] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	ACR70: DB Week 28
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[50]
Method
Parameter type	Difference in percentage
Point estimate	15.21
Confidence interval
level	95%
sides	2-sided
lower limit	-10.05
upper limit	40.46
Notes [50] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	ACR70: DB Week 32
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[51]
Method
Parameter type	Difference in percentage
Point estimate	12.33
Confidence interval
level	95%
sides	2-sided
lower limit	-12.91
upper limit	37.56
Notes [51] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	ACR70: DB Week 36
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[52]
Method
Parameter type	Difference in percentage
Point estimate	9.1
Confidence interval
level	95%
sides	2-sided
lower limit	-16.13
upper limit	34.33
Notes [52] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	ACR90: DB Week 4
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[53]
Method
Parameter type	Difference in percentage
Point estimate	-19.82
Confidence interval
level	95%
sides	2-sided
lower limit	-44.09
upper limit	4.46
Notes [53] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	ACR70: DB Week 52
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[54]
Method
Parameter type	Difference in percentage
Point estimate	12.33
Confidence interval
level	95%
sides	2-sided
lower limit	-12.91
upper limit	37.56
Notes [54] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	ACR70: DB Week 48
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[55]
Method
Parameter type	Difference in percentage
Point estimate	12.33
Confidence interval
level	95%
sides	2-sided
lower limit	-12.91
upper limit	37.56
Notes [55] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	ACR 70: DB Week 44
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[56]
Method
Parameter type	Difference in percentage
Point estimate	12.33
Confidence interval
level	95%
sides	2-sided
lower limit	-12.91
upper limit	37.56
Notes [56] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	ACR90: DB Week 24
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[57]
Method
Parameter type	Difference in percentage
Point estimate	-4.38
Confidence interval
level	95%
sides	2-sided
lower limit	-26.02
upper limit	17.26
Notes [57] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	ACR90: DB Week 8
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[58]
Method
Parameter type	Difference in percentage
Point estimate	-17.28
Confidence interval
level	95%
sides	2-sided
lower limit	-40.19
upper limit	5.63
Notes [58] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	ACR90: DB Week 12
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[59]
Method
Parameter type	Difference in percentage
Point estimate	-13.71
Confidence interval
level	95%
sides	2-sided
lower limit	-37.19
upper limit	9.77
Notes [59] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	ACR90: DB Week 16
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[60]
Method
Parameter type	Difference in percentage
Point estimate	-4.03
Confidence interval
level	95%
sides	2-sided
lower limit	-26.67
upper limit	18.61
Notes [60] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	ACR90: DB Week 20
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[61]
Method
Parameter type	Difference in percentage
Point estimate	-7.6
Confidence interval
level	95%
sides	2-sided
lower limit	-29.66
upper limit	14.45
Notes [61] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	ACR70: DB Week 40
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[62]
Method
Parameter type	Difference in percentage
Point estimate	12.33
Confidence interval
level	95%
sides	2-sided
lower limit	-12.91
upper limit	37.56
Notes [62] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	ACR90: DB Week 44
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[63]
Method
Parameter type	Difference in percentage
Point estimate	-0.46
Confidence interval
level	95%
sides	2-sided
lower limit	-23.6
upper limit	22.68
Notes [63] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	ACR90: DB Week 40
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[64]
Method
Parameter type	Difference in percentage
Point estimate	-3.69
Confidence interval
level	95%
sides	2-sided
lower limit	-27.16
upper limit	19.78
Notes [64] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	ACR90: DB Week 36
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[65]
Method
Parameter type	Difference in percentage
Point estimate	-6.91
Confidence interval
level	95%
sides	2-sided
lower limit	-30.65
upper limit	16.83
Notes [65] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	ACR90: DB Week 32
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[66]
Method
Parameter type	Difference in percentage
Point estimate	-14.75
Confidence interval
level	95%
sides	2-sided
lower limit	-35.32
upper limit	5.83
Notes [66] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	ACR90: DB Week 28
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[67]
Method
Parameter type	Difference in percentage
Point estimate	-7.95
Confidence interval
level	95%
sides	2-sided
lower limit	-28.89
upper limit	12.99
Notes [67] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	ACR90: DB Week 48
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[68]
Method
Parameter type	Difference in percentage
Point estimate	-0.46
Confidence interval
level	95%
sides	2-sided
lower limit	-23.6
upper limit	22.68
Notes [68] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	ACR100: DB Week 16
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[69]
Method
Parameter type	Difference in percentage
Point estimate	-7.95
Confidence interval
level	95%
sides	2-sided
lower limit	-28.89
upper limit	12.99
Notes [69] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	ACR100: DB Week 12
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[70]
Method
Parameter type	Difference in percentage
Point estimate	-11.52
Confidence interval
level	95%
sides	2-sided
lower limit	-31.65
upper limit	8.61
Notes [70] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	ACR100: DB Week 8
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[71]
Method
Parameter type	Difference in percentage
Point estimate	-18.32
Confidence interval
level	95%
sides	2-sided
lower limit	-37.98
upper limit	1.34
Notes [71] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	ACR100: DB Week 4
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[72]
Method
Parameter type	Difference in percentage
Point estimate	-21.2
Confidence interval
level	95%
sides	2-sided
lower limit	-42.45
upper limit	0.05
Notes [72] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	ACR90: DB Week 52
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[73]
Method
Parameter type	Difference in percentage
Point estimate	-0.46
Confidence interval
level	95%
sides	2-sided
lower limit	-23.6
upper limit	22.68
Notes [73] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	ACR100: DB Week 20
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[74]
Method
Parameter type	Difference in percentage
Point estimate	1.38
Confidence interval
level	95%
sides	2-sided
lower limit	-16.15
upper limit	18.91
Notes [74] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	ACR100: DB Week 24
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[75]
Method
Parameter type	Difference in percentage
Point estimate	-1.5
Confidence interval
level	95%
sides	2-sided
lower limit	-21.36
upper limit	18.37
Notes [75] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	ACR100: DB Week 28
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[76]
Method
Parameter type	Difference in percentage
Point estimate	-8.29
Confidence interval
level	95%
sides	2-sided
lower limit	-27.91
upper limit	11.32
Notes [76] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	ACR100: DB Week 32
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[77]
Method
Parameter type	Difference in percentage
Point estimate	-15.09
Confidence interval
level	95%
sides	2-sided
lower limit	-34.29
upper limit	4.1
Notes [77] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	ACR30: DB Week 44
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[78]
Method
Parameter type	Difference in percentage
Point estimate	9.1
Confidence interval
level	95%
sides	2-sided
lower limit	-16.13
upper limit	34.33
Notes [78] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	ACR100: DB Week 48
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[79]
Method
Parameter type	Difference in percentage
Point estimate	-0.81
Confidence interval
level	95%
sides	2-sided
lower limit	-23.04
upper limit	21.43
Notes [79] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	ACR100: DB Week 44
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[80]
Method
Parameter type	Difference in percentage
Point estimate	-4.38
Confidence interval
level	95%
sides	2-sided
lower limit	-26.02
upper limit	17.26
Notes [80] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	ACR100: DB Week 40
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[81]
Method
Parameter type	Difference in percentage
Point estimate	-7.6
Confidence interval
level	95%
sides	2-sided
lower limit	-29.66
upper limit	14.45
Notes [81] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	ACR100: DB Week 36
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[82]
Method
Parameter type	Difference in percentage
Point estimate	-11.52
Confidence interval
level	95%
sides	2-sided
lower limit	-31.65
upper limit	8.61
Notes [82] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	ACR100: DB Week 52
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[83]
Method
Parameter type	Difference in percentage
Point estimate	-0.81
Confidence interval
level	95%
sides	2-sided
lower limit	-23.04
upper limit	21.43
Notes [83] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.

Secondary: Percentage of Participants with Adapted JIA ACR 30/50/70/90/100 Response at DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52: Double-Blind Phase Top of page

Secondary: Percentage of Participants with Adapted JIA American College of Rheumatology (ACR) 30/50/70/90/100 Response at Part 1 Day 7, Weeks 2, 4, 8, 12, and 16: Open-label Phase Part 1 Top of page
End point title	Percentage of Participants with Adapted JIA American College of Rheumatology (ACR) 30/50/70/90/100 Response at Part 1 Day 7, Weeks 2, 4, 8, 12, and 16: Open-label Phase Part 1 [84]
End point description	Adapted JIA ACR 30,50,70,90,100 response=absence of fever due to sJIA in preceding 7 days along with improvement of >=30%,50%,70%,90%,100%, respectively in at least 3 out of 6 JIA core set variables with no more than 1 JIA core set variable worsening by >=30%. Variables included: number of joints with active arthritis (any joint with swelling, or in absence of swelling, limitation of motion accompanied by either pain on motion or tenderness);number of joints with limited range of motion; physician global evaluation of disease activity on VAS (0: no disease activity-100:very severe disease activity); parent/legal guardian/Child evaluation of overall well-being on VAS (0:very well-100 mm:very poor); functional ability (CHAQ Disability Index) ESR. OLPT1 set used. All participants reported as ‘Number of subjects analysed’ contributed data to table; but may not have evaluable data for every row. “n”: participants evaluable for specified time points & used for calculating percentages.
End point type	Secondary
End point timeframe	Part 1 Day 7, Part 1 Weeks 2, 4, 8, 12, and 16
Notes [84] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint is specific to Open-Label period hence Open-Label arms have been reported.
End point values Tofacitinib 5mg BID Open_Label (OL) Part 1 Number of subjects analysed 100 Units: Percentage of participants number (confidence interval 95%)     ACR30: Part 1 Day 7; n=99 26.26 (17.59 to 34.93)     ACR30:Part 1 Week 2; n=99 42.42 (32.69 to 52.16)     ACR30:Part 1 Week 4; n=97 68.04 (58.76 to 77.32)     ACR30:Part 1 Week 8; n=82 86.59 (79.21 to 93.96)     ACR30:Part 1 Week 12; n=44 90.91 (82.41 to 99.40)     ACR30:Part 1 Week 16; n=24 83.33 (68.42 to 98.24)     ACR50:Part 1 Day 7; n=99 18.18 (10.58 to 25.78)     ACR50:Part 1 Week 2; n=99 28.28 (19.41 to 37.15)     ACR50:Part 1 Week 4; n=97 44.33 (34.44 to 54.22)     ACR50:Part 1 Week 8; n=83 59.04 (48.46 to 69.62)     ACR50:Part 1 Week 12; n=44 79.55 (67.63 to 91.46)     ACR50:Part 1 Week 16; n=24 75.00 (57.68 to 92.32)     ACR70:Part 1 Day 7; n=99 10.10 (4.16 to 16.04)     ACR70:Part 1 Week 2; n=99 16.16 (8.91 to 23.41)     ACR70:Part 1 Week 4; n=97 19.59 (11.69 to 27.49)     ACR70:Part 1 Week 8; n=82 34.15 (23.88 to 44.41)     ACR70:Part 1 Week 12; n=44 38.64 (24.25 to 53.02)     ACR70:Part 1 Week 16; n=24 33.33 (14.47 to 52.19)     ACR90:Part 1 Day 7; n=99 5.05 (0.74 to 9.36)     ACR90:Part 1 Week 2; n=99 6.06 (1.36 to 10.76)     ACR90:Part 1 Week 4; n=97 11.34 (5.03 to 17.65)     ACR90:Part 1 Week 8; n=82 18.29 (9.92 to 26.66)     ACR90:Part 1 Week 12; n=44 15.91 (5.10 to 26.72)     ACR90:Part 1 Week 16; n=24 16.67 (1.76 to 31.58)     ACR100:Part 1 Day 7; n=99 3.03 (0 to 6.41)     ACR100:Part 1 Week 2; n=99 5.05 (0.74 to 9.36)     ACR100:Part 1 Week 4; n=97 8.25 (2.77 to 13.72)     ACR100:Part 1 Week 8; n=82 13.41 (6.04 to 20.79)     ACR100:Part 1 Week 12; n=44 9.09 (0.60 to 17.59)     ACR100:Part 1 Week 16; n=24 8.33 (0 to 19.39)
No statistical analyses for this end point

Secondary: Percentage of Participants with Adapted JIA American College of Rheumatology (ACR) 30/50/70/90/100 Response at Part 1 Day 7, Weeks 2, 4, 8, 12, and 16: Open-label Phase Part 1 Top of page

Secondary: Percentage of Participants with Adapted JIA ACR 30/50/70/90/100 Response at Part 2 Weeks 4, 8, 12, 16, 20 and 24: Open-label Phase Part 2 Top of page
End point title	Percentage of Participants with Adapted JIA ACR 30/50/70/90/100 Response at Part 2 Weeks 4, 8, 12, 16, 20 and 24: Open-label Phase Part 2 [85]
End point description	Adapted JIA ACR 30,50,70,90,100 response=absence of fever due to sJIA in preceding 7 days along with improvement of >=30%,50%,70%,90%,100%, respectively in at least 3 out of 6 JIA core set variables with no more than 1 JIA core set variable worsening by >=30%. Variables included: number of joints with active arthritis (i.e. any joint with swelling, or in absence of swelling, limitation of motion accompanied by either pain on motion or tenderness);number of joints with limited range of motion; physician global evaluation of disease activity on a VAS from 0=no disease activity to 100=very severe disease activity; parent/ legal guardian/Child evaluation of overall well-being on VAS from 0= very well to 100 mm= very poor; functional ability (CHAQ disability Index) ESR. OLPT2 analysis set was used. Here, n=number of participants evaluable for the specified time points and used for calculating percentages.
End point type	Secondary
End point timeframe	Part 2 Weeks 4, 8, 12, 16, 20 and 24
Notes [85] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint is specific to Open-Label period hence Open-Label arms have been reported.
End point values Tofacitinib 5mg BID OL Part 2 Number of subjects analysed 54 Units: Percentage of participants number (confidence interval 95%)     ACR30:Part 2 Week 4; n=50 90.00 (81.68 to 98.32)     ACR30:Part 2 Week 8;n-=40 87.50 (77.25 to 97.75)     ACR30:Part 2 Week 12; n=31 90.32 (79.91 to 100)     ACR30:Part 2 week 16;n=23 86.96 (73.19 to 100)     ACR30:Part 2 Week 20;n=13 100 (100 to 100)     ACR30:Part 2 Week 24;n=3 100 (100 to 100)     ACR50:Part 2 Week 4;n=50 86.00 (76.38 to 95.62)     ACR50:Part 2 Week 8;n=40 77.50 (64.56 to 90.44)     ACR50:Part 2 Week 12;n=31 80.65 (66.74 to 94.55)     ACR50:Part 2 Week 16;n=23 73.91 (55.97 to 91.86)     ACR50:Part 2 Week 20;n=13 92.31 (77.82 to 100)     ACR50:Part 2 Week 24;n=3 100 (100 to 100)     ACR70:Part 2 Week 4;n=50 68.00 (55.07 to 80.93)     ACR70:Part 2 Week 8;n=40 67.50 (52.98 to 82.02)     ACR70:Part 2 Week 12;n=31 70.97 (54.99 to 86.95)     ACR70:Part 2 Week 16;n=23 73.91 (55.97 to 91.86)     ACR70:Part 2 Week 20;-n-13 92.31 (77.82 to 100)     ACR70:Part 2 Week 24;n=3 66.67 (13.32 to 100)     ACR90:Part 2 Week 4;n=50 32.00 (19.07 to 44.93)     ACR90:Part 2 Week 8;n=40 27.50 (13.66 to 41.34)     ACR90:Part 2 Week 12;n=31 22.58 (7.86 to 37.30)     ACR90:Part 2 Week 16;n=23 34.78 (15.32 to 54.25)     ACR90:Part 2 Week 20;n=13 53.85 (26.75 to 80.95)     ACR90:Part 2 Week 24;n=3 33.33 (0 to 86.68)     ACR100:Part 2 Week 4;n=50 28.00 (15.55 to 40.45)     ACR100:Part 2 Week 8;n=40 27.50 (13.66 to 41.34)     ACR100:Part 2 Week 12;n=31 16.13 (3.18 to 29.08)     ACR100:Part 2 Week 16;n=23 26.09 (8.14 to 44.03)     ACR100:Part 2 Week 20;n=13 38.46 (12.01 to 64.91)     ACR100:Part 2 Week 24;n=3 33.33 (0 to 86.68)
No statistical analyses for this end point

Secondary: Percentage of Participants with Adapted JIA ACR 30/50/70/90/100 Response at Part 2 Weeks 4, 8, 12, 16, 20 and 24: Open-label Phase Part 2 Top of page

Secondary: Percentage of Participants With C-reactive protein (CRP) <= 10 mg/L at Baseline, Part 1 Days 3, 7, Weeks 2, 4, 8, 12, 16: Open-label Phase Part 1 Top of page
End point title	Percentage of Participants With C-reactive protein (CRP) <= 10 mg/L at Baseline, Part 1 Days 3, 7, Weeks 2, 4, 8, 12, 16: Open-label Phase Part 1 [86]
End point description	Percentage of participants with CRP <= 10 milligrams per liter (mg/L) along with 95% CI based on normal approximation is reported in this endpoint. OLPT1 analysis set included all participants who were enrolled into the open-label part 1 phase of the study and received at least one dose of investigational product in part 1. All participants reported under ‘Number of Participants Analysed’ contributed data to the table; however, may not have evaluable data for every row. Here, n=number of participants evaluable for the specified time points and used for calculating percentages.
End point type	Secondary
End point timeframe	Baseline (last value collected prior to Day 1 of study treatment), Part 1 Days 3, 7, Part 1 Weeks 2, 4, 8, 12, 16
Notes [86] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint is specific to Open-Label period hence Open-Label arms have been reported.
End point values Tofacitinib 5mg BID Open_Label (OL) Part 1 Number of subjects analysed 100 Units: Percentage of participants number (confidence interval 95%)     Baseline; n=100 30.00 (21.02 to 38.98)     Part 1 Day 3; n=95 32.63 (23.20 to 42.06)     Part 1 Day 7; n=97 45.36 (35.45 to 55.27)     Part 1 Week 2; n=97 49.48 (39.53 to 59.43)     Part 1 Week 4; n=97 55.67 (45.78 to 65.56)     Part 1 Week 8; n=80 60.00 (49.26 to 70.74)     Part 1 Week 12; n=44 59.09 (44.56 to 73.62)     Part 1 Week 16; n=24 41.67 (21.94 to 61.39)
No statistical analyses for this end point

Secondary: Percentage of Participants With C-reactive protein (CRP) <= 10 mg/L at Baseline, Part 1 Days 3, 7, Weeks 2, 4, 8, 12, 16: Open-label Phase Part 1 Top of page

Secondary: Percentage of Participants with Fever Attributed to sJIA at Part 1 Days 3, 7 and 14: Open-label Phase Part 1 Top of page
End point title	Percentage of Participants with Fever Attributed to sJIA at Part 1 Days 3, 7 and 14: Open-label Phase Part 1 [87]
End point description	Fever was defined as an oral temperature of ˃38 degree Celsius/100.4 degree Fahrenheit. 95% CI was based on normal approximation. OLPT1 analysis set included all participants who were enrolled into the open-label part 1 phase of the study and received at least one dose of investigational product in part 1. All participants reported under ‘Number of Subjects Analysed’ contributed data to the table; however, may not have evaluable data for every row. Here, n=number of participants evaluable for the specified time points and used for calculating percentages.
End point type	Secondary
End point timeframe	Part 1 Days 3, 7 and 14
Notes [87] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint is specific to Open-Label period hence Open-Label arms have been reported.
End point values Tofacitinib 5mg BID Open_Label (OL) Part 1 Number of subjects analysed 100 Units: Percentage of participants number (confidence interval 95%)     Part 1 Day 3; n=96 3.13 (0 to 6.61)     Part 1 Day 7; n=97 1.03 (0 to 3.04)     Part 1 Day 14; n=97 4.12 (0.17 to 8.08)
No statistical analyses for this end point

Secondary: Percentage of Participants with Fever Attributed to sJIA at Part 1 Days 3, 7 and 14: Open-label Phase Part 1 Top of page

Secondary: Percentage of Participants With C-reactive protein (CRP) <= 10 mg/L at Part 2 Weeks 4, 8, 12, 16, 20, 24: Open-label Phase Part 2 Top of page
End point title	Percentage of Participants With C-reactive protein (CRP) <= 10 mg/L at Part 2 Weeks 4, 8, 12, 16, 20, 24: Open-label Phase Part 2 [88]
End point description	Percentage of participants with CRP <= 10 mg/L along with 95% CI based on normal approximation is reported in this endpoint. OLPT2 analysis set included all participants who were enrolled into the open-label part 2 phase of the study and received at least one dose of investigational product in part 2. All participants reported under ‘Number of Participants Analysed’ contributed data to the table; however, may not have evaluable data for every row. Here, n=number of participants evaluable for the specified time points and used for calculating percentages.
End point type	Secondary
End point timeframe	Part 2 Weeks 4, 8, 12, 16, 20, 24
Notes [88] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint is specific to Open-Label period hence Open-Label arms have been reported.
End point values Tofacitinib 5mg BID OL Part 2 Number of subjects analysed 54 Units: Percentage of participants number (confidence interval 95%)     Part 2 Week 4; n=50 68.00 (55.07 to 80.93)     Part 2 Week 8; n=40 62.50 (47.50 to 77.50)     Part 2 Week 12; n=31 51.61 (34.02 to 69.21)     Part 2 Week 16; n=22 54.55 (33.74 to 75.35)     Part 2 Week 20; n=13 76.92 (54.02 to 99.83)     Part 2 Week 24; n=3 33.33 (0 to 86.68)
No statistical analyses for this end point

Secondary: Percentage of Participants With C-reactive protein (CRP) <= 10 mg/L at Part 2 Weeks 4, 8, 12, 16, 20, 24: Open-label Phase Part 2 Top of page

Secondary: Percentage of Participants With Absence of Fever due to sJIA at Part 1 Day 7, Weeks 2, 4, 8, 12, 16: Open-label Phase Part 1 Top of page
End point title	Percentage of Participants With Absence of Fever due to sJIA at Part 1 Day 7, Weeks 2, 4, 8, 12, 16: Open-label Phase Part 1 [89]
End point description	Percentage of participants with absence of fever along with 95% CI based on normal approximation is reported in this endpoint. OLPT1 analysis set included all participants who were enrolled into the open-label part 1 phase of the study and received at least one dose of investigational product in part 1. All participants reported under ‘Number of Participants Analysed’ contributed data to the table; however, may not have evaluable data for every row. Here, n=number of participants evaluable for the specified time points and used for calculating percentages.
End point type	Secondary
End point timeframe	Part 1 Day 7, Part 1 Weeks 2, 4, 8, 12, 16
Notes [89] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint is specific to Open-Label period hence Open-Label arms have been reported.
End point values Tofacitinib 5mg BID Open_Label (OL) Part 1 Number of subjects analysed 100 Units: Percentage of participants number (confidence interval 95%)     Part 1 Day 7; n=97 83.51 (76.12 to 90.89)     Part 1 Week 2; n=97 82.47 (74.91 to 90.04)     Part 1 Week 4; n=97 90.72 (84.95 to 96.50)     Part 1 Week 8; n=83 96.39 (92.37 to 100)     Part 1 Week 12; n=44 100 (100 to 100)     Part 1 Week 16; n=24 95.83 (87.84 to 100)
No statistical analyses for this end point

Secondary: Percentage of Participants With Absence of Fever due to sJIA at Part 1 Day 7, Weeks 2, 4, 8, 12, 16: Open-label Phase Part 1 Top of page

Secondary: Percentage of Participants With Absence of Fever due to sJIA at Part 2 Weeks 4, 8, 12, 16, 20, 24: Open-label Phase Part 2 Top of page
End point title	Percentage of Participants With Absence of Fever due to sJIA at Part 2 Weeks 4, 8, 12, 16, 20, 24: Open-label Phase Part 2 [90]
End point description	Percentage of participants with absence of fever along with 95% CI based on normal approximation is reported in this endpoint. OLPT2 analysis set included all participants who were enrolled into the open-label part 2 phase of the study and received at least one dose of investigational product in part 2. All participants reported under ‘Number of Participants Analysed’ contributed data to the table; however, may not have evaluable data for every row. Here, n=number of participants evaluable for the specified time points and used for calculating percentages.
End point type	Secondary
End point timeframe	Part 2 Weeks 4, 8, 12, 16, 20 and 24
Notes [90] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint is specific to Open-Label period hence Open-Label arms have been reported.
End point values Tofacitinib 5mg BID OL Part 2 Number of subjects analysed 54 Units: Percentage of participants number (confidence interval 95%)     Part 2 Week 4; n=50 98.00 (94.12 to 100)     Part 2 Week 8; n=39 92.31 (83.94 to 100)     Part 2 Week 12; n=31 96.77 (90.55 to 100)     Part 2 Week 16; n=22 90.91 (78.90 to 100)     Part 2 Week 20; n=12 100 (100 to 100)     Part 2 Week 24; n=3 100 (100 to 100)
No statistical analyses for this end point

Secondary: Percentage of Participants With Absence of Fever due to sJIA at Part 2 Weeks 4, 8, 12, 16, 20, 24: Open-label Phase Part 2 Top of page

Secondary: Percentage of Participants With Absence of Fever due to sJIA at DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52: Double Blind Phase Top of page
End point title	Percentage of Participants With Absence of Fever due to sJIA at DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52: Double Blind Phase [91]
End point description	Percentage of participants with absence of fever due sJIA is reported in this endpoint. DBFAS consisted of all randomized participants who received at least one dose of investigational product in the double-blind phase. Missing response was imputed as non-response.
End point type	Secondary
End point timeframe	DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Notes [91] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint is specific to Double-Blind period hence Double-Blind arms have been reported.
End point values Tofacitinib 5mg BID Double-Blind (DB) Placebo DB Number of subjects analysed 28 31 Units: Percentage of participants number (not applicable)     DB Week 4 85.71 93.55     DB Week 8 85.71 80.65     DB Week 12 75.00 74.19     DB Week 16 71.43 61.29     DB Week 20 67.86 51.61     DB Week 24 64.29 54.84     DB Week 28 60.71 51.61     DB Week 32 60.71 51.61     DB Week 36 60.71 51.61     DB Week 40 60.71 51.61     DB Week 44 60.71 51.61     DB Week 48 60.71 48.39     DB Week 52 60.71 48.39
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 4
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[92]
Method
Parameter type	Difference in percentage
Point estimate	-7.83
Confidence interval
level	95%
sides	2-sided
lower limit	-23.42
upper limit	7.75
Notes [92] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 12
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[93]
Method
Parameter type	Difference in percentage
Point estimate	0.81
Confidence interval
level	95%
sides	2-sided
lower limit	-21.43
upper limit	23.04
Notes [93] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 16
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[94]
Method
Parameter type	Difference in percentage
Point estimate	10.14
Confidence interval
level	95%
sides	2-sided
lower limit	-13.82
upper limit	34.1
Notes [94] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 20
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[95]
Method
Parameter type	Difference in percentage
Point estimate	16.24
Confidence interval
level	95%
sides	2-sided
lower limit	-8.43
upper limit	40.92
Notes [95] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 24
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[96]
Method
Parameter type	Difference in percentage
Point estimate	9.45
Confidence interval
level	95%
sides	2-sided
lower limit	-15.49
upper limit	34.39
Notes [96] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 52
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[97]
Method
Parameter type	Difference in percentage
Point estimate	12.33
Confidence interval
level	95%
sides	2-sided
lower limit	-12.91
upper limit	37.56
Notes [97] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 32
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[98]
Method
Parameter type	Difference in percentage
Point estimate	9.1
Confidence interval
level	95%
sides	2-sided
lower limit	-16.13
upper limit	34.33
Notes [98] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 36
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[99]
Method
Parameter type	Difference in percentage
Point estimate	9.1
Confidence interval
level	95%
sides	2-sided
lower limit	-16.13
upper limit	34.33
Notes [99] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 40
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[100]
Method
Parameter type	Difference in percentage
Point estimate	9.1
Confidence interval
level	95%
sides	2-sided
lower limit	-16.13
upper limit	34.33
Notes [100] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 44
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[101]
Method
Parameter type	Difference in percentage
Point estimate	9.1
Confidence interval
level	95%
sides	2-sided
lower limit	-16.13
upper limit	34.33
Notes [101] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 48
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[102]
Method
Parameter type	Difference in percentage
Point estimate	12.33
Confidence interval
level	95%
sides	2-sided
lower limit	-12.91
upper limit	37.56
Notes [102] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 8
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[103]
Method
Parameter type	Difference in percentage
Point estimate	5.07
Confidence interval
level	95%
sides	2-sided
lower limit	-13.94
upper limit	24.08
Notes [103] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 28
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[104]
Method
Parameter type	Difference in percentage
Point estimate	9.1
Confidence interval
level	95%
sides	2-sided
lower limit	-16.13
upper limit	34.33
Notes [104] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.

Secondary: Percentage of Participants With Absence of Fever due to sJIA at DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52: Double Blind Phase Top of page

Secondary: Change From Open Label Baseline in Juvenile Arthritis Disease Activity Score (JADAS-27) Erythrocyte Sedimentation Rate (ESR) at Part 1 Day 7, Part 1 Weeks 2, 4, 8, 12 and 16: Open-label Phase Part 1 Top of page
End point title	Change From Open Label Baseline in Juvenile Arthritis Disease Activity Score (JADAS-27) Erythrocyte Sedimentation Rate (ESR) at Part 1 Day 7, Part 1 Weeks 2, 4, 8, 12 and 16: Open-label Phase Part 1 [105]
End point description	JADAS-27 is a validated composite disease activity measure for JIA. JADAS-27 ESR score was determined based on four components: Physician global assessment of disease activity assessed on a VAS of 0 (no activity) to 10 (maximum activity); parent/legal guardian global assessment of well-being (from the CHAQ) (assessed on a VAS of 0 [very well] to 10 [very poor]), ESR (value normalized to 0 to 10 scale) and number of joints with active disease (27 joint assessment ranging from 0 to 27). The overall JADAS-27 score was sum of the 4 components and it ranged from 0 to 57. A higher score indicated more disease activity. OLPT1 analysis set included all participants who were enrolled into the open-label part 1 phase of the study and received at least one dose of investigational product in part 1. All participants reported under “Number of subjects analysed” contributed data to the table; however, may not have evaluable data for every row. Here “n” = participants evaluable for specified rows.
End point type	Secondary
End point timeframe	Baseline (last value collected prior to day 1 of tofacitinib administration in OL phase), Part 1 Day 7, Part 1 Weeks 2, 4, 8, 12 and 16
Notes [105] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint is specific to Open-Label period hence Open-Label arms have been reported.
End point values Tofacitinib 5mg BID Open_Label (OL) Part 1 Number of subjects analysed 100 Units: Units on a scale arithmetic mean (standard deviation)     Part 1 Day 7: n=98 -5.64 ( 5.20 )     Part 1 Week 2: n=98 -8.57 ( 5.97 )     Part 1 Week 4: n=97 -11.95 ( 6.53 )     Part 1 Week 8: n=81 -15.09 ( 7.27 )     Part 1 Week 12: n=44 -15.77 ( 7.24 )     Part 1 Week 16: n=24 -14.08 ( 6.09 )
No statistical analyses for this end point

Secondary: Change From Open Label Baseline in Juvenile Arthritis Disease Activity Score (JADAS-27) Erythrocyte Sedimentation Rate (ESR) at Part 1 Day 7, Part 1 Weeks 2, 4, 8, 12 and 16: Open-label Phase Part 1 Top of page

Secondary: Time to First Adapted JIA ACR 30 Response: Open-label Phase Part 1 Top of page
End point title	Time to First Adapted JIA ACR 30 Response: Open-label Phase Part 1 [106]
End point description	Time to the first adapted JIA ACR 30 response was measured in number of days since Day 1 (day of adapted JIA ACR 30 response – Day 1 + 1) in the Open-Label Phase Part 1. Participants that did not achieve an adapted JIA ACR30 response (absence of fever due to sJIA (temperature ≤38° C/100.4° F) in the preceding 7 days along with an improvement of at least 30% from baseline (Day 1 of study drug before first tofacitinib administration) in at least 3 of the 6 JIA core components, with worsening of > =30 in no more than 1 of the remaining components), which in Part 1 (withdrew from the study) were censored at their last available response assessment in Part 1. OLPT1 analysis set included all participants who were enrolled into the open-label part 1 phase of the study and received at least one dose of investigational product in part 1. 95% CI was based on the Brookmeyer and Crowley Method.
End point type	Secondary
End point timeframe	From Day 1 up to 16 weeks
Notes [106] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint is specific to Open-Label period hence Open-Label arms have been reported.
End point values Tofacitinib 5mg BID Open_Label (OL) Part 1 Number of subjects analysed 100 Units: Days     median (confidence interval 95%) 27.0 (15.0 to 29.0)
No statistical analyses for this end point

Secondary: Time to First Adapted JIA ACR 30 Response: Open-label Phase Part 1 Top of page

Secondary: Change From Open-Label Baseline in JADAS-27 ESR at Part 2 Weeks 4, 8, 12, 16, 20, 24: Open-label Phase Part 2 Top of page
End point title	Change From Open-Label Baseline in JADAS-27 ESR at Part 2 Weeks 4, 8, 12, 16, 20, 24: Open-label Phase Part 2 [107]
End point description	JADAS-27 is a validated composite disease activity measure for JIA. JADAS-27 ESR score was determined based on four components: physician global assessment of disease activity assessed on a VAS of 0 (no activity) to 10 (maximum activity); parent/legal guardian global assessment of well-being (from the CHAQ) (assessed on a VAS of 0 [very well] to 10 [very poor]), ESR (value normalized to 0 to 10 scale) and number of joints with active disease (27 joint assessment ranging from 0 to 27). The overall JADAS-27 score was sum of the 4 components and it ranged from 0 to 57. A higher score indicated more disease activity. DBFAS consisted of all randomised participants who received at least one dose of investigational product in the double-blind phase. All participants reported under “Number of subjects analysed” contributed data to the table; however, may not have evaluable data for every row. Here “n” signifies number of participants evaluable for specified rows.
End point type	Secondary
End point timeframe	Baseline (last value collected prior to day 1 of tofacitinib administration in OL phase), Part 2 Weeks 4, 8, 12, 16, 20 and 24
Notes [107] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint is specific to Open-Label period hence Open-Label arms have been reported.
End point values Tofacitinib 5mg BID OL Part 2 Number of subjects analysed 54 Units: Units on a scale arithmetic mean (standard deviation)     Part 2 Week 4; n=50 -17.05 ( 8.18 )     Part 2 Week 8; n=40 -17.13 ( 8.14 )     Part 2 Week 12; n=31 -18.17 ( 7.74 )     Part 2 Week 16; n=23 -18.89 ( 7.56 )     Part 2 Week 20; n=13 -21.14 ( 5.78 )     Part 2 Week 24; n=3 -22.17 ( 7.58 )
No statistical analyses for this end point

Secondary: Change From Open-Label Baseline in JADAS-27 ESR at Part 2 Weeks 4, 8, 12, 16, 20, 24: Open-label Phase Part 2 Top of page

Secondary: Change From Open-Label Baseline in JADAS-27 CRP at Part 1 Day 7, Part 1 Weeks 2, 4, 8, 12 and 16: Open-label Phase Part 1 Top of page
End point title	Change From Open-Label Baseline in JADAS-27 CRP at Part 1 Day 7, Part 1 Weeks 2, 4, 8, 12 and 16: Open-label Phase Part 1 [108]
End point description	JADAS-27 is a validated composite disease activity measure for JIA. JADAS-27 CRP score was determined based on four components: physician global assessment of disease activity assessed on a VAS of 0 (no activity) to 10 (maximum activity); parent/legal guardian global assessment of well-being (from the CHAQ) (assessed on a VAS of 0 [very well] to 10 [very poor]), CRP (value normalized to 0 to 10 scale) and number of joints with active disease (27 joint assessment ranging from 0 to 27). The overall JADAS-27 score was sum of the 4 components and it ranged from 0 to 57. A higher score indicated more disease activity. OLPT1 analysis set included all participants who were enrolled into the open-label part 1 phase of the study and received at least one dose of investigational product in part 1. All participants reported under “Number of subjects analysed” contributed data to the table; however, may not have evaluable data for every row. Here “n” = participants evaluable for specified rows.
End point type	Secondary
End point timeframe	Baseline (last value collected prior to day 1 of tofacitinib administration in OL phase), Part 1 Day 7, Part 1 Weeks 2, 4, 8, 12 and 16
Notes [108] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint is specific to Open-Label period hence Open-Label arms have been reported.
End point values Tofacitinib 5mg BID Open_Label (OL) Part 1 Number of subjects analysed 100 Units: Units on a scale arithmetic mean (standard deviation)     Part 1 Day 7; n=97 -6.25 ( 5.53 )     Part 1 Week 2; n=96 -8.55 ( 6.10 )     Part 1 Week 4; n=97 -11.88 ( 7.28 )     Part 1 Week 8; n=80 -15.07 ( 8.46 )     Part 1 Week 12; n=44 -15.19 ( 7.73 )     Part 1 Week 16; n=24 -13.10 ( 6.37 )
No statistical analyses for this end point

Secondary: Change From Open-Label Baseline in JADAS-27 CRP at Part 1 Day 7, Part 1 Weeks 2, 4, 8, 12 and 16: Open-label Phase Part 1 Top of page

Secondary: Change From Open-Label Baseline in JADAS-27 CRP at Part 2 Weeks 4, 8, 12, 16, 20, 24: Open-label Phase Part 2 Top of page
End point title	Change From Open-Label Baseline in JADAS-27 CRP at Part 2 Weeks 4, 8, 12, 16, 20, 24: Open-label Phase Part 2 [109]
End point description	JADAS-27 is a validated composite disease activity measure for JIA. JADAS-27 CRP score was determined based on four components: physician global assessment of disease activity assessed on a VAS of 0 (no activity) to 10 (maximum activity); parent/legal guardian global assessment of well-being (from the CHAQ) (assessed on a VAS of 0 [very well] to 10 [very poor]), CRP (value normalized to 0 to 10 scale) and number of joints with active disease (27 joint assessment ranging from 0 to 27). The overall JADAS-27 score was sum of the 4 components and it ranged from 0 to 57. A higher score indicated more disease activity. OLPT2 analysis set included all participants who were enrolled into the open-label part 2 phase of the study and received at least one dose of investigational product in part 2. All participants reported under “Number of subjects analysed” contributed data to the table; however, may not have evaluable data for every row. Here “n” = participants evaluable for specified rows.
End point type	Secondary
End point timeframe	Baseline (last value collected prior to day 1 of tofacitinib administration in OL phase), Part 2 Weeks 4, 8, 12, 16, 20 and 24
Notes [109] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint is specific to Open-Label period hence Open-Label arms have been reported.
End point values Tofacitinib 5mg BID OL Part 2 Number of subjects analysed 54 Units: Units on a scale arithmetic mean (standard deviation)     Part 2 Week 4; n=50 -17.16 ( 8.87 )     Part 2 Week 8; n=40 -17.44 ( 8.03 )     Part 2 Week 12; n=31 -18.99 ( 7.67 )     Part 2 Week 16; n=22 -20.31 ( 6.41 )     Part 2 Week 20; n=13 -22.16 ( 7.05 )     Part 2 Week 24; n=3 -25.61 ( 9.82 )
No statistical analyses for this end point

Secondary: Change From Open-Label Baseline in JADAS-27 CRP at Part 2 Weeks 4, 8, 12, 16, 20, 24: Open-label Phase Part 2 Top of page

Secondary: Change From Double-Blind Baseline in JADAS-27 ESR at DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52: Double-blind Phase Top of page
End point title	Change From Double-Blind Baseline in JADAS-27 ESR at DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52: Double-blind Phase [110]
End point description	JADAS-27 is a validated composite disease activity measure for JIA. JADAS-27 ESR score was determined based on four components: Physician global assessment of disease activity assessed on a VAS of 0 (no activity) to 10 (maximum activity); parent/legal guardian global assessment of well-being (from the CHAQ) (assessed on a VAS of 0 [very well] to 10 [very poor]), ESR (value normalized to 0 to 10 scale) and number of joints with active disease (27 joint assessment ranging from 0 to 27). The overall JADAS-27 score was sum of the 4 components and it ranged from 0 to 57. A higher score indicated more disease activity. DBFAS consisted of all randomised participants who received at least one dose of investigational product in the double-blind phase. All participants reported under “Number of subjects analysed” contributed data to the table; however, may not have evaluable data for every row. Here “n” signifies number of participants evaluable for specified rows.
End point type	Secondary
End point timeframe	DB Baseline (at randomization on Day 1 in DB phase), DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Notes [110] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint is specific to Double-Blind period hence Double-Blind arms have been reported.
End point values Tofacitinib 5mg BID Double-Blind (DB) Placebo DB Number of subjects analysed 28 31 Units: Units on a scale least squares mean (standard error)     DB Week 4; (n=27,30) 1.07 ( 0.84 ) 1.08 ( 0.79 )     DB Week 8; (n=25,24) 1.75 ( 1.08 ) 0.81 ( 1.06 )     DB Week 12; (n=21,22) 1.47 ( 1.46 ) 1.71 ( 1.40 )     DB Week 16; (n=21,19) 0.43 ( 1.03 ) 1.29 ( 1.04 )     DB Week 20; (n=19,14) -1.04 ( 0.65 ) 0.05 ( 0.69 )     DB Week 24; (n=18,14) -0.49 ( 0.57 ) -0.79 ( 0.60 )     DB Week 28; (n=17,12) 2.58 ( 2.05 ) 3.86 ( 2.25 )     DB Week 32; (n=13,10) -0.21 ( 0.77 ) -0.68 ( 0.83 )     DB Week 36; (n=13,10) -1.52 ( 0.50 ) -1.26 ( 0.54 )     DB Week 40; (n=11,9) -0.23 ( 0.91 ) -0.96 ( 0.96 )     DB Week 44; (n=10,9) -1.67 ( 0.75 ) -0.83 ( 0.79 )     DB Week 48; (n=8,5) -2.29 ( 0.38 ) -2.06 ( 0.60 )     DB Week 52; (n=6,4) -2.41 ( 0.60 ) -1.65 ( 1.07 )
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 16
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[111]
Method
Parameter type	Difference in LS Mean
Point estimate	-0.86
Confidence interval
level	95%
sides	2-sided
lower limit	-3.99
upper limit	2.28
Notes [111] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 12
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[112]
Method
Parameter type	Difference in LS Mean
Point estimate	-0.24
Confidence interval
level	95%
sides	2-sided
lower limit	-4.54
upper limit	4.06
Notes [112] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 8
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[113]
Method
Parameter type	Difference in LS Mean
Point estimate	0.94
Confidence interval
level	95%
sides	2-sided
lower limit	-2.25
upper limit	4.12
Notes [113] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 4
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[114]
Method
Parameter type	Difference in LS Mean
Point estimate	-0.01
Confidence interval
level	95%
sides	2-sided
lower limit	-2.4
upper limit	2.38
Notes [114] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 36
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[115]
Method
Parameter type	Difference in LS Mean
Point estimate	-0.26
Confidence interval
level	95%
sides	2-sided
lower limit	-1.86
upper limit	1.35
Notes [115] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 40
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[116]
Method
Parameter type	Difference in LS Mean
Point estimate	0.73
Confidence interval
level	95%
sides	2-sided
lower limit	-2.18
upper limit	3.63
Notes [116] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 44
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[117]
Method
Parameter type	Difference in LS Mean
Point estimate	-0.83
Confidence interval
level	95%
sides	2-sided
lower limit	-3.22
upper limit	1.56
Notes [117] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 48
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[118]
Method
Parameter type	Difference in LS Mean
Point estimate	-0.23
Confidence interval
level	95%
sides	2-sided
lower limit	-1.76
upper limit	1.3
Notes [118] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 32
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[119]
Method
Parameter type	Difference in LS Mean
Point estimate	0.48
Confidence interval
level	95%
sides	2-sided
lower limit	-1.98
upper limit	2.93
Notes [119] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 52
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[120]
Method
Parameter type	Difference in LS Mean
Point estimate	-0.75
Confidence interval
level	95%
sides	2-sided
lower limit	-3.43
upper limit	1.93
Notes [120] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 24
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[121]
Method
Parameter type	Difference in LS Mean
Point estimate	0.3
Confidence interval
level	95%
sides	2-sided
lower limit	-1.46
upper limit	2.06
Notes [121] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 20
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[122]
Method
Parameter type	Difference in LS Mean
Point estimate	-1.09
Confidence interval
level	95%
sides	2-sided
lower limit	-3.12
upper limit	0.94
Notes [122] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 28
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[123]
Method
Parameter type	Difference in LS Mean
Point estimate	-1.28
Confidence interval
level	95%
sides	2-sided
lower limit	-7.85
upper limit	5.29
Notes [123] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.

Secondary: Change From Double-Blind Baseline in JADAS-27 ESR at DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52: Double-blind Phase Top of page

Secondary: Change From Double-Blind Baseline in JADAS-27 CRP at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52: Double-blind Phase Top of page
End point title	Change From Double-Blind Baseline in JADAS-27 CRP at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52: Double-blind Phase [124]
End point description	JADAS-27 is a validated composite disease activity measure for JIA. JADAS-27 CRP score was determined based on four components: Physician global assessment of disease activity assessed on a VAS of 0 (no activity) to 10 (maximum activity); parent/legal guardian global assessment of well-being (from the CHAQ) (assessed on a VAS of 0 [very well] to 10 [very poor]), CRP (value normalized to 0 to 10 scale) and number of joints with active disease (27 joint assessment ranging from 0 to 27). The overall JADAS-27 score was sum of the 4 components and it ranged from 0 to 57. A higher score indicated more disease activity. DBFAS consisted of all randomised participants who received at least one dose of investigational product in the double-blind phase. All participants reported under “Number of subjects analysed” contributed data to the table; however, may not have evaluable data for every row. Here “n” signifies number of participants evaluable for specified rows.
End point type	Secondary
End point timeframe	DB Baseline (at randomization on Day 1 in DB phase), DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Notes [124] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint is specific to Double-Blind period hence Double-Blind arms have been reported.
End point values Tofacitinib 5mg BID Double-Blind (DB) Placebo DB Number of subjects analysed 28 31 Units: Units on a scale least squares mean (standard error)     DB Week 4; (n=26,31) 1.62 ( 0.96 ) 0.71 ( 0.90 )     DB Week 8; (n=25,25) 2.12 ( 0.95 ) 0.01 ( 0.93 )     DB Week 12; (n=21,22) 1.78 ( 1.46 ) 1.80 ( 1.40 )     DB Week 16; (n=21,19) 0.84 ( 1.09 ) 1.95 ( 1.08 )     DB Week 20; (n=19,15) -0.17 ( 0.84 ) 0.36 ( 0.87 )     DB Week 24; (n=18,15) 1.58 ( 1.04 ) -0.26 ( 1.08 )     DB Week 28; (n=17,12) 2.64 ( 1.86 ) 2.72 ( 2.04 )     DB Week 32; (n=12,9) 0.49 ( 0.99 ) 1.18 ( 1.07 )     DB Week 36; (n=13,10) -1.59 ( 0.50 ) -1.24 ( 0.53 )     DB Week 40; (n=11,9) 0.38 ( 1.15 ) 0.41 ( 1.21 )     DB Week 44; (n=10,9) -1.09 ( 0.99 ) 1.50 ( 1.02 )     DB Week 48; (n=8,5) -2.04 ( 0.51 ) -1.23 ( 0.76 )     DB Week 52; (n=6,4) -2.31 ( 0.60 ) -1.85 ( 1.10 )
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 4
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[125]
Method
Parameter type	Difference in LS Mean
Point estimate	0.9
Confidence interval
level	95%
sides	2-sided
lower limit	-1.8
upper limit	3.61
Notes [125] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 8
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[126]
Method
Parameter type	Difference in LS Mean
Point estimate	2.11
Confidence interval
level	95%
sides	2-sided
lower limit	-0.64
upper limit	4.86
Notes [126] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 12
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[127]
Method
Parameter type	Difference in LS Mean
Point estimate	-0.02
Confidence interval
level	95%
sides	2-sided
lower limit	-4.25
upper limit	4.21
Notes [127] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 16
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[128]
Method
Parameter type	Difference in LS Mean
Point estimate	-1.12
Confidence interval
level	95%
sides	2-sided
lower limit	-4.32
upper limit	2.09
Notes [128] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 20
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[129]
Method
Parameter type	Difference in LS Mean
Point estimate	-0.53
Confidence interval
level	95%
sides	2-sided
lower limit	-3.04
upper limit	1.98
Notes [129] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 24
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[130]
Method
Parameter type	Difference in LS Mean
Point estimate	1.84
Confidence interval
level	95%
sides	2-sided
lower limit	-1.29
upper limit	4.97
Notes [130] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 28
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[131]
Method
Parameter type	Difference in LS Mean
Point estimate	-0.08
Confidence interval
level	95%
sides	2-sided
lower limit	-5.89
upper limit	5.72
Notes [131] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 40
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[132]
Method
Parameter type	Difference in LS Mean
Point estimate	-0.03
Confidence interval
level	95%
sides	2-sided
lower limit	-3.63
upper limit	3.58
Notes [132] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 36
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[133]
Method
Parameter type	Difference in LS Mean
Point estimate	-0.35
Confidence interval
level	95%
sides	2-sided
lower limit	-1.89
upper limit	1.19
Notes [133] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 32
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[134]
Method
Parameter type	Difference in LS Mean
Point estimate	-0.69
Confidence interval
level	95%
sides	2-sided
lower limit	-3.79
upper limit	2.41
Notes [134] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 44
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[135]
Method
Parameter type	Difference in LS Mean
Point estimate	-2.59
Confidence interval
level	95%
sides	2-sided
lower limit	-5.67
upper limit	0.49
Notes [135] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 48
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[136]
Method
Parameter type	Difference in LS Mean
Point estimate	-0.82
Confidence interval
level	95%
sides	2-sided
lower limit	-2.82
upper limit	1.19
Notes [136] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 52
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[137]
Method
Parameter type	Difference in LS Mean
Point estimate	-0.46
Confidence interval
level	95%
sides	2-sided
lower limit	-3.27
upper limit	2.36
Notes [137] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.

Secondary: Change From Double-Blind Baseline in JADAS-27 CRP at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52: Double-blind Phase Top of page

Secondary: Change From Open-Label Baseline in Number of Joints with Active Arthritis at Part 2 Weeks 4, 8, 12, 16, 20, 24: Open-label Phase Part 2 Top of page
End point title	Change From Open-Label Baseline in Number of Joints with Active Arthritis at Part 2 Weeks 4, 8, 12, 16, 20, 24: Open-label Phase Part 2 [138]
End point description	The ACR defined a joint with active arthritis as a joint with swelling or, in the absence of swelling, limitation of motion accompanied by pain on motion, or tenderness. OLPT2 analysis set included all participants who were enrolled into the open-label part 2 phase of the study and received at least one dose of investigational product in part 2. All participants reported under ‘Number of Participants Analysed’ contributed data to the table; however, may not have evaluable data for every row. Here, “n” signifies number of participants evaluable for specified rows.
End point type	Secondary
End point timeframe	Baseline (last value collected prior to day 1 of tofacitinib administration in OL phase), Part 2 Weeks 4, 8, 12, 16, 20, 24
Notes [138] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint is specific to Open-Label period hence Open-Label arms have been reported.
End point values Tofacitinib 5mg BID OL Part 2 Number of subjects analysed 54 Units: Joints arithmetic mean (standard deviation)     Part 2 Week 4; n=50 -7.78 ( 7.78 )     Part 2 Week 8; n=40 -7.73 ( 8.40 )     Part 2 Week 12; n=31 -9.26 ( 7.98 )     Part 2 Week 16; n=23 -10.00 ( 7.99 )     Part 2 Week 20; n=13 -10.85 ( 7.83 )     Part 2 Week 24; n=3 -13.67 ( 11.02 )
No statistical analyses for this end point

Secondary: Change From Open-Label Baseline in Number of Joints with Active Arthritis at Part 2 Weeks 4, 8, 12, 16, 20, 24: Open-label Phase Part 2 Top of page

Secondary: Change From Open-Label Baseline in Number of Joints with Active Arthritis at Part 1 Day 7, Weeks 2, 4, 8, 12, 16: Open-label Phase Part 1 Top of page
End point title	Change From Open-Label Baseline in Number of Joints with Active Arthritis at Part 1 Day 7, Weeks 2, 4, 8, 12, 16: Open-label Phase Part 1 [139]
End point description	The ACR defined a joint with active arthritis as a joint with swelling or, in the absence of swelling, limitation of motion accompanied by pain on motion, or tenderness. OLPT1 analysis set included all participants who were enrolled into the open-label part 1 phase of the study and received at least one dose of investigational product in part 1. All participants reported under “Number of subjects analysed” contributed data to the table; however, may not have evaluable data for every row. Here, “n” signifies number of participants evaluable for specified rows.
End point type	Secondary
End point timeframe	Baseline (last value collected prior to day 1 of tofacitinib administration in OL phase), Part 1 Day 7, Part 1 Weeks 2, 4, 8, 12 and 16
Notes [139] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint is specific to Open-Label period hence Open-Label arms have been reported.
End point values Tofacitinib 5mg BID Open_Label (OL) Part 1 Number of subjects analysed 100 Units: Joints arithmetic mean (standard deviation)     Part 1 Day 7; n=99 -2.96 ( 4.17 )     Part 1 Week 2; n=99 -4.21 ( 5.31 )     Part 1 Week 4; n=97 -6.03 ( 6.04 )     Part 1 Week 8; n=83 -7.80 ( 9.25 )     Part 1 Week 12; n=44 -7.52 ( 7.38 )     Part 1 Week 16; n=24 -6.38 ( 7.87 )
No statistical analyses for this end point

Secondary: Change From Open-Label Baseline in Number of Joints with Active Arthritis at Part 1 Day 7, Weeks 2, 4, 8, 12, 16: Open-label Phase Part 1 Top of page

Secondary: Change From Open-Label Baseline in Number of Joints with Limited Range of Motion at Part 1 Day 7, Weeks 2, 4, 8, 12, 16: Open-label Phase Part 1 Top of page
End point title	Change From Open-Label Baseline in Number of Joints with Limited Range of Motion at Part 1 Day 7, Weeks 2, 4, 8, 12, 16: Open-label Phase Part 1 [140]
End point description	The ACR defined a joint with active arthritis as a joint with swelling or, in the absence of swelling, limitation of motion accompanied by pain on motion, or tenderness. OLPT1 analysis set included all participants who were enrolled into the open-label part 1 phase of the study and received at least one dose of investigational product in part 1. All participants reported under ‘Number of Participants Analysed’ contributed data to the table; however, may not have evaluable data for every row. Here, “n” signifies number of participants evaluable for specified rows.
End point type	Secondary
End point timeframe	Baseline (last value collected prior to day 1 of tofacitinib administration in OL phase), Part 1 Day 7, Weeks 2, 4, 8, 12, 16
Notes [140] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint is specific to Open-Label period hence Open-Label arms have been reported.
End point values Tofacitinib 5mg BID Open_Label (OL) Part 1 Number of subjects analysed 100 Units: Joints arithmetic mean (standard deviation)     Part 1 Day 7; n=99 -1.83 ( 4.26 )     Part 1 Week 2; n=99 -2.06 ( 4.70 )     Part 1 Week 4; n=97 -2.90 ( 5.42 )     Part 1 Week 8; n=83 -4.36 ( 8.59 )     Part 1 Week 12; n=44 -3.64 ( 6.05 )     Part 1 Week 16; n=24 -2.33 ( 3.48 )
No statistical analyses for this end point

Secondary: Change From Open-Label Baseline in Number of Joints with Limited Range of Motion at Part 1 Day 7, Weeks 2, 4, 8, 12, 16: Open-label Phase Part 1 Top of page

Secondary: Change From Open-Label Baseline in Number of Joints with Limited Range of Motion at Part 2 Weeks 4, 8, 12, 16, 20, 24: Open-label Phase Part 2 Top of page
End point title	Change From Open-Label Baseline in Number of Joints with Limited Range of Motion at Part 2 Weeks 4, 8, 12, 16, 20, 24: Open-label Phase Part 2 [141]
End point description	The ACR defined a joint with active arthritis as a joint with swelling or, in the absence of swelling, limitation of motion accompanied by pain on motion, or tenderness. OLPT2 analysis set included all participants who were enrolled into the open-label part 2 phase of the study and received at least one dose of investigational product in part 2. All participants reported under ‘Number of Participants Analysed’ contributed data to the table; however, may not have evaluable data for every row. Here, “n” signifies number of participants evaluable for specified rows.
End point type	Secondary
End point timeframe	Baseline (last value collected prior to day 1 of tofacitinib administration in OL phase), Part 2 Weeks 4, 8, 12, 16, 20, 24
Notes [141] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint is specific to Open-Label period hence Open-Label arms have been reported.
End point values Tofacitinib 5mg BID OL Part 2 Number of subjects analysed 54 Units: Joints arithmetic mean (standard deviation)     Part 2 Week 4; n=50 -4.26 ( 6.75 )     Part 2 Week 8; n=40 -3.90 ( 6.08 )     Part 2 Week 12; n=31 -5.81 ( 7.48 )     Part 2 Week 16; n=23 -5.74 ( 7.13 )     Part 2 Week 20; n=13 -5.92 ( 9.32 )     Part 2 Week 24; n=3 -15.67 ( 11.02 )
No statistical analyses for this end point

Secondary: Change From Open-Label Baseline in Number of Joints with Limited Range of Motion at Part 2 Weeks 4, 8, 12, 16, 20, 24: Open-label Phase Part 2 Top of page

Secondary: Change From Open-Label Baseline in Physician Global Evaluation of Disease Activity at Part 1 Day 7, Weeks 2, 4, 8, 12, 16: Open-label Phase Part 1 Top of page
End point title	Change From Open-Label Baseline in Physician Global Evaluation of Disease Activity at Part 1 Day 7, Weeks 2, 4, 8, 12, 16: Open-label Phase Part 1 [142]
End point description	Physician global evaluation of disease activity was assessed on a VAS ranging from 0 to 10 mm, where 0=no activity and 10=maximum activity. OLPT1 analysis set included all participants who were enrolled into the open-label part 1 phase of the study and received at least one dose of investigational product in part 1. All participants reported under ‘Number of Participants Analysed’ contributed data to the table; however, may not have evaluable data for every row. Here, “n” signifies number of participants evaluable for specified rows.
End point type	Secondary
End point timeframe	Baseline (last value collected prior to day 1 of tofacitinib administration in OL phase), Part 1 Day 7, Weeks 2, 4, 8, 12, 16
Notes [142] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint is specific to Open-Label period hence Open-Label arms have been reported.
End point values Tofacitinib 5mg BID Open_Label (OL) Part 1 Number of subjects analysed 100 Units: Units on a scale arithmetic mean (standard deviation)     Part 1 Day 7; n=99 -1.18 ( 1.36 )     Part 1 Week 2; n=99 -1.82 ( 1.68 )     Part 1 Week 4; n=97 -2.62 ( 1.75 )     Part 1 Week 8; n=83 -3.40 ( 2.01 )     Part 1 Week 12; n=44 -3.66 ( 2.08 )     Part 1 Week 16; n=24 -3.50 ( 1.93 )
No statistical analyses for this end point

Secondary: Change From Open-Label Baseline in Physician Global Evaluation of Disease Activity at Part 1 Day 7, Weeks 2, 4, 8, 12, 16: Open-label Phase Part 1 Top of page

Secondary: Change From Open-Label Baseline in Physician Global Evaluation of Disease Activity at Part 2 Weeks 4, 8, 12, 16, 20, 24: Open-label Phase Part 2 Top of page
End point title	Change From Open-Label Baseline in Physician Global Evaluation of Disease Activity at Part 2 Weeks 4, 8, 12, 16, 20, 24: Open-label Phase Part 2 [143]
End point description	Physician global evaluation of disease activity was assessed on a VAS ranging from 0 to 10 mm, where 0=no activity and 10=maximum activity. OLPT2 analysis set included all participants who were enrolled into the open-label part 2 phase of the study and received at least one dose of investigational product in part 2. All participants reported under ‘Number of Participants Analysed’ contributed data to the table; however, may not have evaluable data for every row. Here “n” signifies number of participants evaluable for specified rows.
End point type	Secondary
End point timeframe	Baseline (last value collected prior to day 1 of tofacitinib administration in OL phase), Part 2 Weeks 4, 8, 12, 16, 20, 24
Notes [143] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint is specific to Open-Label period hence Open-Label arms have been reported.
End point values Tofacitinib 5mg BID OL Part 2 Number of subjects analysed 54 Units: Units on a scale arithmetic mean (standard deviation)     Part 2 Week 4; n=50 -4.54 ( 2.10 )     Part 2 Week 8; n=40 -4.53 ( 1.74 )     Part 2 Week 12; n=31 -4.65 ( 1.57 )     Part 2 Week 16; n=23 -4.89 ( 1.77 )     Part 2 Week 20; n=13 -5.62 ( 1.21 )     Part 2 Week 24; n=3 -6.17 ( 1.44 )
No statistical analyses for this end point

Secondary: Change From Open-Label Baseline in Physician Global Evaluation of Disease Activity at Part 2 Weeks 4, 8, 12, 16, 20, 24: Open-label Phase Part 2 Top of page

Secondary: Change From Open-Label Baseline in ESR at Part 2 Weeks 4, 8, 12, 16, 20, 24: Open-label Phase Part 2 Top of page
End point title	Change From Open-Label Baseline in ESR at Part 2 Weeks 4, 8, 12, 16, 20, 24: Open-label Phase Part 2 [144]
End point description	ESR was determined using an ESR testing kit. OLPT2 analysis set included all participants who were enrolled into the open-label part 2 phase of the study and received at least one dose of investigational product in part 2. All participants reported under ‘Number of Participants Analysed’ contributed data to the table; however, may not have evaluable data for every row. Here “n” signifies number of participants evaluable for specified rows.
End point type	Secondary
End point timeframe	Baseline (last value collected prior to day 1 of tofacitinib administration in OL phase), Part 2 Weeks 4, 8, 12, 16, 20, 24
Notes [144] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint is specific to Open-Label period hence Open-Label arms have been reported.
End point values Tofacitinib 5mg BID OL Part 2 Number of subjects analysed 54 Units: Millimeter per hour arithmetic mean (standard deviation)     Part 2 Week 4; n=50 -33.64 ( 28.16 )     Part 2 Week 8; n=40 -30.73 ( 27.11 )     Part 2 Week 12; n=31 -27.52 ( 28.13 )     Part 2 Week 16; n=23 -23.48 ( 24.70 )     Part 2 Week 20; n=13 -37.54 ( 20.93 )     Part 2 Week 24; n=3 -24.33 ( 6.03 )
No statistical analyses for this end point

Secondary: Change From Open-Label Baseline in ESR at Part 2 Weeks 4, 8, 12, 16, 20, 24: Open-label Phase Part 2 Top of page

Secondary: Change From Open-Label Baseline in ESR at Part 1 Day 7, Weeks 2, 4, 8, 12, 16: Open-label Phase Part 1 Top of page
End point title	Change From Open-Label Baseline in ESR at Part 1 Day 7, Weeks 2, 4, 8, 12, 16: Open-label Phase Part 1 [145]
End point description	ESR was determined using an ESR testing kit. OLPT1 analysis set included all participants who were enrolled into the open-label part 1 phase of the study and received at least one dose of investigational product in part 1. All participants reported under ‘Number of Participants Analysed’ contributed data to the table; however, may not have evaluable data for every row. Here, “n” signifies number of participants evaluable for specified rows.
End point type	Secondary
End point timeframe	Baseline (last value collected prior to day 1 of tofacitinib administration in OL phase), Part 1 Day 7, Weeks 2, 4, 8, 12, 16
Notes [145] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint is specific to Open-Label period hence Open-Label arms have been reported.
End point values Tofacitinib 5mg BID Open_Label (OL) Part 1 Number of subjects analysed 100 Units: Millimeter per hour arithmetic mean (standard deviation)     Part 1 Day 7; n=98 -11.00 ( 16.96 )     Part 1 Week 2; n=99 -18.60 ( 19.78 )     Part 1 Week 4; n=97 -24.70 ( 23.86 )     Part 1 Week 8; n=81 -30.59 ( 23.12 )     Part 1 Week 12; n=44 -31.74 ( 21.75 )     Part 1 Week 16; n=24 -27.65 ( 28.84 )
No statistical analyses for this end point

Secondary: Change From Open-Label Baseline in ESR at Part 1 Day 7, Weeks 2, 4, 8, 12, 16: Open-label Phase Part 1 Top of page

Secondary: Change From Open-Label Baseline in Child Health Assessment Questionnaire (CHAQ)- Parental Evaluation of Overall Well-being at Part 1 Days 3, 7, Part 1 Weeks 2, 4, 8, 12, 16: Open-label Phase Part 1 Top of page
End point title	Change From Open-Label Baseline in Child Health Assessment Questionnaire (CHAQ)- Parental Evaluation of Overall Well-being at Part 1 Days 3, 7, Part 1 Weeks 2, 4, 8, 12, 16: Open-label Phase Part 1 [146]
End point description	The CHAQ, derived from the adult health assessment questionnaire, comprised of two indices disability and discomfort, and parent global assessment of overall well-being. For assessment of overall well-being, the parent/legal guardian/participant were required to rate the overall well-being by entering a number from 0 to 10 (in 0.5 increments), on a 21-circle visual analog scale (VAS) where ‘0= Very Well and 10=Very Poorly. OLPT1 analysis set included all participants who were enrolled into the open-label part 1 phase of the study and received at least one dose of investigational product in part 1. All participants reported under ‘Number of Participants Analysed’ contributed data to the table; however, may not have evaluable data for every row. Here, “n” signifies number of participants evaluable for specified rows.
End point type	Secondary
End point timeframe	Baseline (last value collected prior to day 1 of tofacitinib administration in OL phase), Part 1 Days 3,7, Part 1 Weeks 2, 4, 8, 12, 16
Notes [146] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint is specific to Open-Label period hence Open-Label arms have been reported.
End point values Tofacitinib 5mg BID Open_Label (OL) Part 1 Number of subjects analysed 100 Units: Units on a scale arithmetic mean (standard deviation)     Part 1 Day 3; n=96 -0.73 ( 1.53 )     Part 1 Day 7; n=99 -1.36 ( 1.91 )     Part 1 Week 2; n=98 -1.96 ( 1.89 )     Part 1 Week 4; n=97 -2.65 ( 2.44 )     Part 1 Week 8; n=83 -3.35 ( 2.38 )     Part 1 Week 12; n=44 -3.45 ( 2.45 )     Part 1 Week 16; n=24 -3.48 ( 2.78 )
No statistical analyses for this end point

Secondary: Change From Open-Label Baseline in Child Health Assessment Questionnaire (CHAQ)- Parental Evaluation of Overall Well-being at Part 1 Days 3, 7, Part 1 Weeks 2, 4, 8, 12, 16: Open-label Phase Part 1 Top of page

Secondary: Change From Open-Label Baseline in CHAQ - Parental Evaluation of Overall Well-being at Part 2 Weeks 4, 8, 12, 16, 20, 24: Open-label Phase Part 2 Top of page
End point title	Change From Open-Label Baseline in CHAQ - Parental Evaluation of Overall Well-being at Part 2 Weeks 4, 8, 12, 16, 20, 24: Open-label Phase Part 2 [147]
End point description	The CHAQ, derived from the adult health assessment questionnaire, comprised of two indices disability and discomfort, and parent global assessment of overall well-being. For assessment of overall well-being, the parent/legal guardian/participant were required to rate the overall well-being by entering a number from 0 to 10 (in 0.5 increments), on a 21-circle VAS where ‘0= Very Well and 10=Very Poorly. OLPT2 analysis set included all participants who were enrolled into the open-label part 2 phase of the study and received at least one dose of investigational product in part 2. All participants reported under ‘Number of Participants Analysed’ contributed data to the table; however, may not have evaluable data for every row. Here “n” signifies number of participants evaluable for specified rows.
End point type	Secondary
End point timeframe	Baseline (last value collected prior to day 1 of tofacitinib administration in OL phase), Part 2 Weeks 4, 8, 12, 16, 20, 24
Notes [147] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint is specific to Open-Label period hence Open-Label arms have been reported.
End point values Tofacitinib 5mg BID OL Part 2 Number of subjects analysed 54 Units: Units on a scale arithmetic mean (standard deviation)     Part 2 Week 4; n=50 -4.09 ( 2.68 )     Part 2 Week 8; n=40 -4.50 ( 2.88 )     Part 2 Week 12; n=31 -4.73 ( 2.83 )     Part 2 Week 16; n=23 -5.11 ( 2.50 )     Part 2 Week 20; n=13 -5.65 ( 2.89 )     Part 2 Week 24; n=3 -6.33 ( 2.31 )
No statistical analyses for this end point

Secondary: Change From Open-Label Baseline in CHAQ - Parental Evaluation of Overall Well-being at Part 2 Weeks 4, 8, 12, 16, 20, 24: Open-label Phase Part 2 Top of page

Secondary: Change From Open-Label Baseline in CHAQ - Disability Index at Part 1 Day 7, Weeks 2, 4, 8, 12, 16: Open-label Phase Part 1 Top of page
End point title	Change From Open-Label Baseline in CHAQ - Disability Index at Part 1 Day 7, Weeks 2, 4, 8, 12, 16: Open-label Phase Part 1 [148]
End point description	CHAQ, derived from the adult health assessment questionnaire, comprised of two indices disability and discomfort, and parent global assessment of overall Well-being. CHAQ disability index consisted of 30 items in 8 areas: 1. dressing and grooming, 2. arising, 3. eating, 4. walking, 5. hygiene, 6. reach, 7. grip, and 8. activities distributed. Each item was rated on a 4-point scale, scored from 0 (no difficulty) to 3 (unable to do). The eight areas of the CHAQ were averaged to calculate the total disability index score which ranged from 0 (no or minimal physical dysfunction) to 3 (very severe physical dysfunction), higher scores indicated more disability. A participant must have score for at least six of the eight areas, otherwise a CHAQ-DI score was not valid. OLP1 set was used. All participants reported under “Number of subjects analysed” contributed data to the table; however, may not have evaluable data for every row. Here, “n”:number of participants evaluable for specified rows.
End point type	Secondary
End point timeframe	Baseline (last value collected prior to day 1 of tofacitinib administration in OL phase), Part 1 Day 7, Weeks 2, 4, 8, 12, 16
Notes [148] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint is specific to Open-Label period hence Open-Label arms have been reported.
End point values Tofacitinib 5mg BID Open_Label (OL) Part 1 Number of subjects analysed 100 Units: Units on a scale arithmetic mean (standard deviation)     Part 1 Day 7; n=99 -0.21 ( 0.35 )     Part 1 Week 2; n=99 -0.38 ( 0.43 )     Part 1 Week 4; n=97 -0.52 ( 0.56 )     Part 1 Week 8; n=83 -0.59 ( 0.57 )     Part 1 Week 12; n=44 -0.51 ( 0.56 )     Part 1 Week 16; n=24 -0.74 ( 0.73 )
No statistical analyses for this end point

Secondary: Change From Open-Label Baseline in CHAQ - Disability Index at Part 1 Day 7, Weeks 2, 4, 8, 12, 16: Open-label Phase Part 1 Top of page

Secondary: Change From Open-Label Baseline in CHAQ - Disability Index at Part 2 Weeks 4, 8, 12, 16, 20, 24: Open-label Phase Part 2 Top of page
End point title	Change From Open-Label Baseline in CHAQ - Disability Index at Part 2 Weeks 4, 8, 12, 16, 20, 24: Open-label Phase Part 2 [149]
End point description	CHAQ, derived from the adult health assessment questionnaire, comprised of two indices disability and discomfort, and parent global assessment of overall well-being. CHAQ disability index consisted of 30 items in 8 areas, 1. dressing and grooming, 2. arising, 3. eating, 4. walking, 5. hygiene, 6. reach, 7. grip, and 8. activities distributed. Each item was rated on a 4-point scale, scored from 0 (no difficulty) to-3 (unable to do). The eight areas of the CHAQ were averaged to calculate the total disability index score which ranged from 0 (no or minimal physical dysfunction) to 3 (very severe physical dysfunction), higher scores indicated more disability. A participant must have score for at least six of the eight areas, otherwise a CHAQ-DI score was not valid. OLPT2 set was used. All participants reported under “Number of subjects analysed” contributed data to the table; however, may not have evaluable data for every row. Here, “n”:number of participants evaluable for specified rows.
End point type	Secondary
End point timeframe	Baseline (last value collected prior to day 1 of tofacitinib administration in OL phase), Part 2 Weeks 4, 8, 12, 16, 20, 24
Notes [149] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint is specific to Open-Label period hence Open-Label arms have been reported.
End point values Tofacitinib 5mg BID OL Part 2 Number of subjects analysed 54 Units: Units on a scale arithmetic mean (standard deviation)     Part 2 Week 4; n=50 -0.79 ( 0.63 )     Part 2 Week 8; n=40 -0.78 ( 0.76 )     Part 2 Week 12; n=31 -0.85 ( 0.80 )     Part 2 Week 16; n=23 -0.67 ( 0.74 )     Part 2 Week 20; n=13 -0.93 ( 0.77 )     Part 2 Week 24; n=3 -0.96 ( 0.92 )
No statistical analyses for this end point

Secondary: Change From Open-Label Baseline in CHAQ - Disability Index at Part 2 Weeks 4, 8, 12, 16, 20, 24: Open-label Phase Part 2 Top of page

Secondary: Change From Open-Label Baseline in Number of Joints with Active Arthritis at DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52: Double-blind Phase Top of page
End point title	Change From Open-Label Baseline in Number of Joints with Active Arthritis at DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52: Double-blind Phase [150]
End point description	The ACR defined a joint with active arthritis as a joint with swelling or, in the absence of swelling, limitation of motion accompanied by pain on motion, or tenderness. DBFAS consisted of all randomised participants who received at least one dose of investigational product in the double-blind phase. All participants reported under ‘Number of Participants Analysed’ contributed data to the table; however, may not have evaluable data for every row. Here, “n” signifies number of participants evaluable for specified rows.
End point type	Secondary
End point timeframe	OL Baseline (last value collected prior to Day 1 of tofacitinib administration in OL phase), DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Notes [150] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint is specific to Open-Label period hence Open-Label arms have been reported.
End point values Tofacitinib 5mg BID Double-Blind (DB) Placebo DB Number of subjects analysed 28 31 Units: Joints least squares mean (standard error)     DB Week 4 (n=27,31) -6.53 ( 0.34 ) -7.39 ( 0.32 )     DB Week 8(n=25,25) -6.36 ( 0.38 ) -7.69 ( 0.38 )     DB Week 12 (n=21,23) -5.92 ( 0.80 ) -7.36 ( 0.76 )     DB Week 16 (n=21,20) -7.34 ( 0.25 ) -7.37 ( 0.25 )     DB Week 20 (n=19,15) -7.41 ( 0.18 ) -7.51 ( 0.20 )     DB Week 24 (n=18,15) -7.33 ( 0.13 ) -7.76 ( 0.13 )     DB Week 28 (n=17,12) -6.36 ( 0.59 ) -6.56 ( 0.67 )     DB Week 32 (n=13,10) -7.27 ( 0.17 ) -7.76 ( 0.19 )     DB Week 36 (n=13,10) -7.43 ( 0.14 ) -7.78 ( 0.16 )     DB Week 40(n=11,9) -7.06 ( 0.24 ) -7.58 ( 0.27 )     DB Week 44 (n=10, 9) -7.39 ( 0.33 ) -7.20 ( 0.35 )     DB Week 48 (n=8, 5) -7.54 ( 0.20 ) -7.75 ( 0.25 )     DB Week 52 (n=6, 5) -7.46 ( 0.26 ) -7.51 ( 0.28 )
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 12
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[151]
Method
Parameter type	Difference in LS Mean
Point estimate	1.43
Confidence interval
level	95%
sides	2-sided
lower limit	-0.79
upper limit	3.66
Notes [151] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Open-Label baseline value, and Open-Label baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 8
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[152]
Method
Parameter type	Difference in LS Mean
Point estimate	1.32
Confidence interval
level	95%
sides	2-sided
lower limit	0.25
upper limit	2.4
Notes [152] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Open-Label baseline value, and Open-Label baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 4
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[153]
Method
Parameter type	Difference in LS Mean
Point estimate	0.86
Confidence interval
level	95%
sides	2-sided
lower limit	-0.08
upper limit	1.79
Notes [153] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Open-Label baseline value, and Open-Label baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 52
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[154]
Method
Parameter type	Difference in LS Mean
Point estimate	0.06
Confidence interval
level	95%
sides	2-sided
lower limit	-0.8
upper limit	0.92
Notes [154] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Open-Label baseline value, and Open-Label baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 32
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[155]
Method
Parameter type	Difference in LS Mean
Point estimate	0.49
Confidence interval
level	95%
sides	2-sided
lower limit	-0.04
upper limit	1.03
Notes [155] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Open-Label baseline value, and Open-Label baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 36
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[156]
Method
Parameter type	Difference in LS Mean
Point estimate	0.35
Confidence interval
level	95%
sides	2-sided
lower limit	-0.09
upper limit	0.79
Notes [156] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Open-Label baseline value, and Open-Label baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 40
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[157]
Method
Parameter type	Difference in LS Mean
Point estimate	0.52
Confidence interval
level	95%
sides	2-sided
lower limit	-0.23
upper limit	1.28
Notes [157] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Open-Label baseline value, and Open-Label baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 44
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[158]
Method
Parameter type	Difference in LS Mean
Point estimate	-0.19
Confidence interval
level	95%
sides	2-sided
lower limit	-1.2
upper limit	0.83
Notes [158] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Open-Label baseline value, and Open-Label baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 48
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[159]
Method
Parameter type	Difference in LS Mean
Point estimate	0.21
Confidence interval
level	95%
sides	2-sided
lower limit	-0.49
upper limit	0.91
Notes [159] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Open-Label baseline value, and Open-Label baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 24
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[160]
Method
Parameter type	Difference in LS Mean
Point estimate	0.44
Confidence interval
level	95%
sides	2-sided
lower limit	0.06
upper limit	0.81
Notes [160] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Open-Label baseline value, and Open-Label baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 20
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[161]
Method
Parameter type	Difference in LS Mean
Point estimate	0.11
Confidence interval
level	95%
sides	2-sided
lower limit	-0.43
upper limit	0.64
Notes [161] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Open-Label baseline value, and Open-Label baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 16
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[162]
Method
Parameter type	Difference in LS Mean
Point estimate	0.02
Confidence interval
level	95%
sides	2-sided
lower limit	-0.7
upper limit	0.74
Notes [162] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Open-Label baseline value, and Open-Label baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 28
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[163]
Method
Parameter type	Difference in LS Mean
Point estimate	0.21
Confidence interval
level	95%
sides	2-sided
lower limit	-1.64
upper limit	2.06
Notes [163] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Open-Label baseline value, and Open-Label baseline value by visit interaction.

Secondary: Change From Open-Label Baseline in Number of Joints with Active Arthritis at DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52: Double-blind Phase Top of page

Secondary: Change From Double-Blind Baseline in Number of Joints with Active Arthritis at DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52: Double-blind Phase Top of page
End point title	Change From Double-Blind Baseline in Number of Joints with Active Arthritis at DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52: Double-blind Phase [164]
End point description	The ACR defined a joint with active arthritis as a joint with swelling or, in the absence of swelling, limitation of motion accompanied by pain on motion, or tenderness. DBFAS consisted of all randomised participants who received at least one dose of investigational product in the double-blind phase. Participants were reported under the treatment they were randomised. All participants reported under ‘Number of Participants Analysed’ contributed data to the table; however, may not have evaluable data for every row. Here, “n” signifies number of participants evaluable for specified rows.
End point type	Secondary
End point timeframe	DB Baseline (randomization), DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Notes [164] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint is specific to Double-Blind period hence Double-Blind arms have been reported.
End point values Tofacitinib 5mg BID Double-Blind (DB) Placebo DB Number of subjects analysed 28 31 Units: Joints least squares mean (standard error)     DB Week 4 (n=27,31) 0.38 ( 0.26 ) 0.09 ( 0.24 )     DB Week 8 (n=25,25) 0.78 ( 0.38 ) -0.23 ( 0.37 )     DB Week 12 (n=21,23) 1.47 ( 0.85 ) 0.22 ( 0.81 )     DB Week 16(n=21,20) 0.05 ( 0.27 ) -0.05 ( 0.27 )     DB Week 20(n=19,15) -0.15 ( 0.15 ) -0.02 ( 0.17 )     DB Week 24 (n=18,15) -0.06 ( 0.12 ) -0.39 ( 0.13 )     DB Week 28 (n=17,12) 0.71 ( 0.70 ) 0.88 ( 0.84 )     DB Week 32 (n=13,10) 0.01 ( 0.18 ) -0.41 ( 0.20 )     DB Week 36 (n=13,10) -0.14 ( 0.15 ) -0.47 ( 0.17 )     DB Week 40 (n=11,9) 0.31 ( 0.25 ) -0.37 ( 0.28 )     DB Week 44(n=10, 9) -0.05 ( 0.35 ) 0.11 ( 0.38 )     DB Week 48(n=8, 5) -0.20 ( 0.21 ) -0.56 ( 0.27 )     DB Week 52(n=6, 5) -0.14 ( 0.28 ) -0.38 ( 0.34 )
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	other [165]
Method
Parameter type	Difference in LS Mean
Point estimate	1.25
Confidence interval
level	95%
sides	2-sided
lower limit	-1.13
upper limit	3.64
Notes [165] - DB Week 12
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[166]
Method
Parameter type	Difference in LS Mean
Point estimate	1.01
Confidence interval
level	95%
sides	2-sided
lower limit	-0.06
upper limit	2.08
Notes [166] - DB Week 8
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	other [167]
Method
Parameter type	Difference in LS Mean
Point estimate	0.29
Confidence interval
level	95%
sides	2-sided
lower limit	-0.43
upper limit	1
Notes [167] - DB Week 4
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	other [168]
Method
Parameter type	Difference in LS Mean
Point estimate	0.32
Confidence interval
level	95%
sides	2-sided
lower limit	-0.03
upper limit	0.68
Notes [168] - DB Week 24
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	other [169]
Method
Parameter type	Difference in LS Mean
Point estimate	-0.13
Confidence interval
level	95%
sides	2-sided
lower limit	-0.58
upper limit	0.33
Notes [169] - DB Week 20
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	other [170]
Method
Parameter type	Difference in LS Mean
Point estimate	0.1
Confidence interval
level	95%
sides	2-sided
lower limit	-0.68
upper limit	0.88
Notes [170] - DB Week 16
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	other [171]
Method
Parameter type	Difference in LS Mean
Point estimate	-0.17
Confidence interval
level	95%
sides	2-sided
lower limit	-2.42
upper limit	2.08
Notes [171] - DB Week 28
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	other [172]
Method
Parameter type	Difference in LS Mean
Point estimate	0.42
Confidence interval
level	95%
sides	2-sided
lower limit	-0.14
upper limit	0.97
Notes [172] - DB Week 32
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	other [173]
Method
Parameter type	Difference in LS Mean
Point estimate	0.32
Confidence interval
level	95%
sides	2-sided
lower limit	-0.15
upper limit	0.79
Notes [173] - DB Week 36
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	other [174]
Method
Parameter type	Difference in LS Mean
Point estimate	0.68
Confidence interval
level	95%
sides	2-sided
lower limit	-0.14
upper limit	1.49
Notes [174] - DB Week 40
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	other [175]
Method
Parameter type	Difference in LS Mean
Point estimate	-0.16
Confidence interval
level	95%
sides	2-sided
lower limit	-1.28
upper limit	0.96
Notes [175] - DB Week 44
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	other [176]
Method
Parameter type	Difference in LS Mean
Point estimate	0.37
Confidence interval
level	95%
sides	2-sided
lower limit	-0.43
upper limit	1.16
Notes [176] - DB Week 48
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 52
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	other [177]
Method
Parameter type	Difference in LS Mean
Point estimate	0.24
Confidence interval
level	95%
sides	2-sided
lower limit	-0.82
upper limit	1.3
Notes [177] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.

Secondary: Change From Double-Blind Baseline in Number of Joints with Active Arthritis at DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52: Double-blind Phase Top of page

Secondary: Change From Open-Label Baseline in Disability Index at DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52: Double-blind Phase Top of page
End point title	Change From Open-Label Baseline in Disability Index at DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52: Double-blind Phase [178]
End point description	The parent was asked to provide responses to questions designed to assessed function in 8 distributed, among a total of 30 items. Each question was rated on a four-point scale, scored from 0-3. The question with the highest score determined the score for the functional area. If aids or devices were used or assistance was required, the minimum score for that was 2. Each question was rated 0 for no difficulty, 1 for some difficulties, 2 for much difficulties, and 3 for unable to do. The 8 areas of the CHAQ were averaged to calculated disability index which was ranges from 0 (no or minimal physical dysfunction) to 3 (very severe physical dysfunction). A participant must have score for at least 6 of the 8 categories, otherwise a CHAQ-DI score was not valid. DBFAS set. All participants reported under “Number of subjects analysed” contributed data to the table; however, may not have evaluable data for every row. Here “n”=number of participants evaluable for specified rows.
End point type	Secondary
End point timeframe	OL Baseline (last value collected prior to Day 1 of tofacitinib administration in OL phase), DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Notes [178] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint is specific to Open-Label period hence Open-Label arms have been reported.
End point values Tofacitinib 5mg BID Double-Blind (DB) Placebo DB Number of subjects analysed 28 31 Units: Units on a scale arithmetic mean (standard deviation)     DB Week 4 (n=27,31) -0.81 ( 0.10 ) -1.03 ( 0.09 )     DB Week 8(n=25,25) -0.93 ( 0.08 ) -1.02 ( 0.08 )     DB Week 12 (n=21,23) -0.99 ( 0.08 ) -1.04 ( 0.07 )     DB Week 16(n=21,20) -0.95 ( 0.09 ) -1.05 ( 0.09 )     DB Week 20 (n=19,15) -1.02 ( 0.07 ) -1.21 ( 0.07 )     DB Week 24(n=18,15) -0.94 ( 0.08 ) -1.05 ( 0.08 )     DB Week 28(n=17,12) -0.94 ( 0.08 ) -1.01 ( 0.09 )     DB Week 32 (n=13,10) -0.96 ( 0.07 ) -1.11 ( 0.07 )     DB Week 36 (n=13,10) -1.05 ( 0.08 ) -1.16 ( 0.09 )     DB Week 40 (n=11,9) -1.07 ( 0.07 ) -1.22 ( 0.08 )     DB Week 44 (n=10, 9) -1.04 ( 0.09 ) -1.08 ( 0.09 )     DB Week 48(n=8, 5) -1.01 ( 0.09 ) -1.10 ( 0.11 )     DB Week 52 (n=6, 5) -1.04 ( 0.10 ) -1.13 ( 0.12 )
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, open-label baseline value, and open-label baseline value by visit interaction.
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	other [179]
Method
Parameter type	Difference in LS Mean
Point estimate	0.09
Confidence interval
level	95%
sides	2-sided
lower limit	-0.15
upper limit	0.32
Notes [179] - DB Week 8
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, open-label baseline value, and open-label baseline value by visit interaction.
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	other [180]
Method
Parameter type	Difference in LS Mean
Point estimate	0.21
Confidence interval
level	95%
sides	2-sided
lower limit	-0.07
upper limit	0.5
Notes [180] - DB Week 4
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, open-label baseline value, and open-label baseline value by visit interaction.
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	other [181]
Method
Parameter type	Difference in LS Mean
Point estimate	0.05
Confidence interval
level	95%
sides	2-sided
lower limit	-0.17
upper limit	0.28
Notes [181] - DB Week 12
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, open-label baseline value, and open-label baseline value by visit interaction.
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	other [182]
Method
Parameter type	Difference in LS Mean
Point estimate	0.1
Confidence interval
level	95%
sides	2-sided
lower limit	-0.16
upper limit	0.36
Notes [182] - DB Week 16
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, open-label baseline value, and open-label baseline value by visit interaction.
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	other [183]
Method
Parameter type	Difference in LS Mean
Point estimate	0.12
Confidence interval
level	95%
sides	2-sided
lower limit	-0.12
upper limit	0.35
Notes [183] - DB Week 24
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, open-label baseline value, and open-label baseline value by visit interaction.
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	other [184]
Method
Parameter type	Difference in LS Mean
Point estimate	0.19
Confidence interval
level	95%
sides	2-sided
lower limit	-0.01
upper limit	0.38
Notes [184] - DB Week 20
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, open-label baseline value, and open-label baseline value by visit interaction.
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	other [185]
Method
Parameter type	Difference in LS Mean
Point estimate	0.07
Confidence interval
level	95%
sides	2-sided
lower limit	-0.18
upper limit	0.31
Notes [185] - DB Week 28
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, open-label baseline value, and open-label baseline value by visit interaction.
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	other [186]
Method
Parameter type	Difference in LS Mean
Point estimate	0.16
Confidence interval
level	95%
sides	2-sided
lower limit	-0.06
upper limit	0.38
Notes [186] - DB Week 40
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, open-label baseline value, and open-label baseline value by visit interaction.
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	other [187]
Method
Parameter type	Difference in LS Mean
Point estimate	0.11
Confidence interval
level	95%
sides	2-sided
lower limit	-0.14
upper limit	0.36
Notes [187] - DB Week 36
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, open-label baseline value, and open-label baseline value by visit interaction.
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	other [188]
Method
Parameter type	Difference in LS Mean
Point estimate	0.15
Confidence interval
level	95%
sides	2-sided
lower limit	-0.06
upper limit	0.37
Notes [188] - DB Week 32
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, open-label baseline value, and open-label baseline value by visit interaction.
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	other [189]
Method
Parameter type	Difference in LS Mean
Point estimate	0.04
Confidence interval
level	95%
sides	2-sided
lower limit	-0.22
upper limit	0.3
Notes [189] - DB Week 44
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, open-label baseline value, and open-label baseline value by visit interaction.
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	other [190]
Method
Parameter type	Difference in LS Mean
Point estimate	0.09
Confidence interval
level	95%
sides	2-sided
lower limit	-0.2
upper limit	0.38
Notes [190] - DB Week 48
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, open-label baseline value, and open-label baseline value by visit interaction.
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	other [191]
Method
Parameter type	Difference in LS Mean
Point estimate	0.09
Confidence interval
level	95%
sides	2-sided
lower limit	-0.24
upper limit	0.42
Notes [191] - DB Week 52

Secondary: Change From Open-Label Baseline in Disability Index at DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52: Double-blind Phase Top of page

Secondary: Change From Double Blind Baseline in Disability Index at DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52: Double-blind Phase Top of page
End point title	Change From Double Blind Baseline in Disability Index at DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52: Double-blind Phase [192]
End point description	The parent was asked to provide responses to questions designed to assessed function in 8 distributed, among a total of 30 items. Each question was rated on a four-point scale, scored from 0-3. The question with the highest score determined the score for the functional area. If aids or devices were used or assistance was required, the minimum score for that was 2. Each question was rated 0 for no difficulty, 1 for some difficulties, 2 for much difficulties, and 3 for unable to do. The 8 areas of the CHAQ were averaged to calculated disability index which was ranges from 0 (no or minimal physical dysfunction) to 3 (very severe physical dysfunction). A participant must have score for at least 6 of the 8 categories, otherwise a CHAQ-DI score was not valid. DBFAS set. All participants reported under “Number of subjects analysed” contributed data to the table; however, may not have evaluable data for every row. Here, “n” =number of participants evaluable for specified rows.
End point type	Secondary
End point timeframe	DB Baseline (randomization), DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Notes [192] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint is specific to Double-Blind period hence Double-Blind arms have been reported.
End point values Tofacitinib 5mg BID Double-Blind (DB) Placebo DB Number of subjects analysed 28 31 Units: Units on a scale least squares mean (standard error)     DB Week 4(n=27,31) 0.04 ( 0.06 ) -0.02 ( 0.06 )     DB Week 8 (n=25,25) -0.03 ( 0.06 ) -0.01 ( 0.06 )     DB Week 12(n=21,23) -0.06 ( 0.06 ) -0.05 ( 0.06 )     DB Week 16(n=21,20) -0.03 ( 0.07 ) -0.05 ( 0.07 )     DB Week 20(n=19,15) -0.08 ( 0.06 ) -0.23 ( 0.06 )     DB Week 24 (n=18,15) 0.06 ( 0.08 ) -0.09 ( 0.08 )     DB Week 28(n=17,12) 0.05 ( 0.08 ) -0.04 ( 0.09 )     DB Week 32(n=13,10) 0.02 ( 0.07 ) -0.13 ( 0.07 )     DB Week 36(n=13,10) -0.03 ( 0.09 ) -0.19 ( 0.09 )     DB Week 40 (n=11,9) -0.09 ( 0.07 ) -0.25 ( 0.07 )     DB Week 44 (n=10, 9) -0.06 ( 0.09 ) -0.10 ( 0.09 )     DB Week 48(n=8, 5) -0.03 ( 0.09 ) -0.19 ( 0.12 )     DB Week 52 (n=6, 5) -0.05 ( 0.10 ) -0.21 ( 0.13 )
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	other [193]
Method
Parameter type	Difference in LS Mean
Point estimate	0.07
Confidence interval
level	95%
sides	2-sided
lower limit	-0.1
upper limit	0.24
Notes [193] - DB Week 4
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	other [194]
Method
Parameter type	Difference in LS Mean
Point estimate	-0.02
Confidence interval
level	95%
sides	2-sided
lower limit	-0.19
upper limit	0.15
Notes [194] - DB Week 8
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	other [195]
Method
Parameter type	Difference in LS Mean
Point estimate	-0.01
Confidence interval
level	95%
sides	2-sided
lower limit	-0.19
upper limit	0.16
Notes [195] - DB Week 12
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	other [196]
Method
Parameter type	Difference in LS Mean
Point estimate	0.01
Confidence interval
level	95%
sides	2-sided
lower limit	-0.2
upper limit	0.23
Notes [196] - DB Week 16
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	other [197]
Method
Parameter type	Difference in LS Mean
Point estimate	0.15
Confidence interval
level	95%
sides	2-sided
lower limit	-0.02
upper limit	0.32
Notes [197] - DB Week 20
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 24
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	other [198]
Method
Parameter type	Difference in LS Mean
Point estimate	0.15
Confidence interval
level	95%
sides	2-sided
lower limit	-0.09
upper limit	0.4
Notes [198] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	other [199]
Method
Parameter type	Difference in LS Mean
Point estimate	0.09
Confidence interval
level	95%
sides	2-sided
lower limit	-0.16
upper limit	0.34
Notes [199] - DB Week 28
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	other [200]
Method
Parameter type	Difference in LS Mean
Point estimate	0.17
Confidence interval
level	95%
sides	2-sided
lower limit	-0.06
upper limit	0.39
Notes [200] - DB Week 40
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	other [201]
Method
Parameter type	Difference in LS Mean
Point estimate	0.16
Confidence interval
level	95%
sides	2-sided
lower limit	-0.1
upper limit	0.43
Notes [201] - DB Week 36
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	other [202]
Method
Parameter type	Difference in LS Mean
Point estimate	0.15
Confidence interval
level	95%
sides	2-sided
lower limit	-0.05
upper limit	0.36
Notes [202] - DB Week 32
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	other [203]
Method
Parameter type	Difference in LS Mean
Point estimate	0.04
Confidence interval
level	95%
sides	2-sided
lower limit	-0.22
upper limit	0.3
Notes [203] - DB Week 44
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	other [204]
Method
Parameter type	Difference in LS Mean
Point estimate	0.15
Confidence interval
level	95%
sides	2-sided
lower limit	-0.18
upper limit	0.49
Notes [204] - DB Week 48
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	other [205]
Method
Parameter type	Difference in LS Mean
Point estimate	0.16
Confidence interval
level	95%
sides	2-sided
lower limit	-0.23
upper limit	0.55
Notes [205] - DB Week 52

Secondary: Change From Double Blind Baseline in Disability Index at DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52: Double-blind Phase Top of page

Secondary: Change From Open-Label Baseline in Number of Joints with Limited Range of Motion at DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52: Double-blind Phase Top of page
End point title	Change From Open-Label Baseline in Number of Joints with Limited Range of Motion at DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52: Double-blind Phase [206]
End point description	The ACR defined a joint with active arthritis as a joint with swelling or, in the absence of swelling, limitation of motion accompanied by pain on motion, or tenderness. DBFAS consisted of all randomised participants who received at least one dose of investigational product in the double-blind phase. All participants reported under ‘Number of Participants Analysed’ contributed data to the table; however, may not have evaluable data for every row. Here, “n” signifies number of participants evaluable for specified rows.
End point type	Secondary
End point timeframe	OL baseline (last value collected prior to day 1 of tofacitinib administration in OL phase), DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Notes [206] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint is specific to Open-Label period hence Open-Label arms have been reported.
End point values Tofacitinib 5mg BID Double-Blind (DB) Placebo DB Number of subjects analysed 28 31 Units: Joints least squares mean (standard error)     DB Week 4 (n=27,31) -2.47 ( 0.43 ) -2.69 ( 0.41 )     DB Week 8 (n=25,25) -2.31 ( 0.45 ) -2.89 ( 0.44 )     DB Week 12(n=21,23) -2.09 ( 0.71 ) -3.29 ( 0.68 )     DB Week 16(n=21,20) -2.76 ( 0.44 ) -2.70 ( 0.43 )     DB Week 20(n=19,15) -2.79 ( 0.19 ) -3.05 ( 0.19 )     DB Week 24(n=18,15) -2.98 ( 0.19 ) -3.07 ( 0.19 )     DB Week 28(n=17,12) -2.56 ( 0.54 ) -2.10 ( 0.56 )     DB Week 32(n=13,10) -2.89 ( 0.18 ) -3.24 ( 0.19 )     DB Week 36(n=13,10) -2.90 ( 0.19 ) -3.21 ( 0.21 )     DB Week 40(n=11,9) -2.96 ( 0.24 ) -3.24 ( 0.25 )     DB Week 44(n=10,9) -2.95 ( 0.25 ) -3.24 ( 0.26 )     DB Week 48(n=8,5) -3.03 ( 0.27 ) -3.25 ( 0.30 )     DB Week 52(n=6,5) -2.75 ( 0.36 ) -3.20 ( 0.36 )
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 8
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[207]
Method
Parameter type	Difference in LS Mean
Point estimate	0.58
Confidence interval
level	95%
sides	2-sided
lower limit	-0.68
upper limit	1.84
Notes [207] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Open label baseline value, and Open-label baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 4
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[208]
Method
Parameter type	Difference in LS Mean
Point estimate	0.21
Confidence interval
level	95%
sides	2-sided
lower limit	-0.97
upper limit	1.4
Notes [208] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Open label baseline value, and Open-label baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 20
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[209]
Method
Parameter type	Difference in LS Mean
Point estimate	0.26
Confidence interval
level	95%
sides	2-sided
lower limit	-0.29
upper limit	0.82
Notes [209] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Open label baseline value, and Open-label baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 24
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[210]
Method
Parameter type	Difference in LS Mean
Point estimate	0.09
Confidence interval
level	95%
sides	2-sided
lower limit	-0.46
upper limit	0.64
Notes [210] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Open label baseline value, and Open-label baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 52
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[211]
Method
Parameter type	Difference in LS Mean
Point estimate	0.45
Confidence interval
level	95%
sides	2-sided
lower limit	-0.66
upper limit	1.57
Notes [211] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Open label baseline value, and Open-label baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 32
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[212]
Method
Parameter type	Difference in LS Mean
Point estimate	0.35
Confidence interval
level	95%
sides	2-sided
lower limit	-0.18
upper limit	0.88
Notes [212] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Open label baseline value, and Open-label baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 36
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[213]
Method
Parameter type	Difference in LS Mean
Point estimate	0.31
Confidence interval
level	95%
sides	2-sided
lower limit	-0.26
upper limit	0.88
Notes [213] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Open label baseline value, and Open-label baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 40
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[214]
Method
Parameter type	Difference in LS Mean
Point estimate	0.28
Confidence interval
level	95%
sides	2-sided
lower limit	-0.43
upper limit	0.99
Notes [214] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Open label baseline value, and Open-label baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 44
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[215]
Method
Parameter type	Difference in LS Mean
Point estimate	0.29
Confidence interval
level	95%
sides	2-sided
lower limit	-0.45
upper limit	1.03
Notes [215] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Open label baseline value, and Open-label baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 48
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[216]
Method
Parameter type	Difference in LS Mean
Point estimate	0.22
Confidence interval
level	95%
sides	2-sided
lower limit	-0.63
upper limit	1.08
Notes [216] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Open label baseline value, and Open-label baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 16
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[217]
Method
Parameter type	Difference in LS Mean
Point estimate	-0.06
Confidence interval
level	95%
sides	2-sided
lower limit	-1.3
upper limit	1.18
Notes [217] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Open label baseline value, and Open-label baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 12
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[218]
Method
Parameter type	Difference in LS Mean
Point estimate	1.2
Confidence interval
level	95%
sides	2-sided
lower limit	-0.77
upper limit	3.16
Notes [218] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Open label baseline value, and Open-label baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 28
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[219]
Method
Parameter type	Difference in LS Mean
Point estimate	-0.46
Confidence interval
level	95%
sides	2-sided
lower limit	-2.05
upper limit	1.13
Notes [219] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Open label baseline value, and Open-label baseline value by visit interaction.

Secondary: Change From Open-Label Baseline in Number of Joints with Limited Range of Motion at DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52: Double-blind Phase Top of page

Secondary: Change From Double-Blind Baseline in Number of Joints with Limited Range of Motion at DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52: Double-blind Phase Top of page
End point title	Change From Double-Blind Baseline in Number of Joints with Limited Range of Motion at DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52: Double-blind Phase [220]
End point description	The ACR defined a joint with active arthritis as a joint with swelling or, in the absence of swelling, limitation of motion accompanied by pain on motion, or tenderness. DBFAS consisted of all randomised participants who received at least one dose of investigational product in the double-blind phase. All participants reported under ‘Number of Participants Analysed’ contributed data to the table; however, may not have evaluable data for every row. Here, “n” signifies number of participants evaluable for specified rows.
End point type	Secondary
End point timeframe	DB Baseline (values at randomization), DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Notes [220] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint is specific to Double-Blind period hence Double-Blind arms have been reported.
End point values Tofacitinib 5mg BID Double-Blind (DB) Placebo DB Number of subjects analysed 28 31 Units: Joints least squares mean (standard error)     DB Week 4 (n=27,31) 0.08 ( 0.22 ) 0.21 ( 0.20 )     DB Week 8 (n=25,25) 0.45 ( 0.42 ) 0.06 ( 0.42 )     DB Week 12 (n=21,23) 0.48 ( 0.44 ) -0.23 ( 0.42 )     DB Week 16 (n=21,20) -0.30 ( 0.17 ) 0.10 ( 0.17 )     DB Week 20 (n=19,15) -0.36 ( 0.10 ) -0.19 ( 0.11 )     DB Week 24(n=18,15) -0.53 ( 0.10 ) -0.22 ( 0.11 )     DB Week 28 (n=17,12) -0.05 ( 0.40 ) 1.05 ( 0.46 )     DB Week 32 (n=13,10) -0.41 ( 0.10 ) -0.48 ( 0.12 )     DB Week 36 (n=13,10) -0.48 ( 0.09 ) -0.46 ( 0.10 )     DB Week 40 (n=11,9) -0.48 ( 0.15 ) -0.43 ( 0.17 )     DB Week 44 (n=10, 9) -0.47 ( 0.16 ) -0.43 ( 0.17 )     DB Week 48(n=8, 5) -0.50 ( 0.20 ) -0.47 ( 0.24 )     DB Week 52 (n=6, 5) -0.21 ( 0.31 ) -0.42 ( 0.33 )
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 4
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[221]
Method
Parameter type	Difference in LS Mean
Point estimate	-0.13
Confidence interval
level	95%
sides	2-sided
lower limit	-0.73
upper limit	0.47
Notes [221] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 8
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[222]
Method
Parameter type	Difference in LS Mean
Point estimate	0.39
Confidence interval
level	95%
sides	2-sided
lower limit	-0.81
upper limit	1.59
Notes [222] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 12
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[223]
Method
Parameter type	Difference in LS Mean
Point estimate	0.7
Confidence interval
level	95%
sides	2-sided
lower limit	-0.54
upper limit	1.95
Notes [223] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 16
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[224]
Method
Parameter type	Difference in LS Mean
Point estimate	-0.4
Confidence interval
level	95%
sides	2-sided
lower limit	-0.9
upper limit	0.1
Notes [224] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 20
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[225]
Method
Parameter type	Difference in LS Mean
Point estimate	-0.16
Confidence interval
level	95%
sides	2-sided
lower limit	-0.46
upper limit	0.13
Notes [225] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 24
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[226]
Method
Parameter type	Difference in LS Mean
Point estimate	-0.32
Confidence interval
level	95%
sides	2-sided
lower limit	-0.63
upper limit	-0.01
Notes [226] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 28
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[227]
Method
Parameter type	Difference in LS Mean
Point estimate	-1.09
Confidence interval
level	95%
sides	2-sided
lower limit	-2.34
upper limit	0.15
Notes [227] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 32
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[228]
Method
Parameter type	Difference in LS Mean
Point estimate	0.07
Confidence interval
level	95%
sides	2-sided
lower limit	-0.26
upper limit	0.4
Notes [228] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 36
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[229]
Method
Parameter type	Difference in LS Mean
Point estimate	-0.02
Confidence interval
level	95%
sides	2-sided
lower limit	-0.3
upper limit	0.26
Notes [229] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 40
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[230]
Method
Parameter type	Difference in LS Mean
Point estimate	-0.05
Confidence interval
level	95%
sides	2-sided
lower limit	-0.53
upper limit	0.43
Notes [230] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 44
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[231]
Method
Parameter type	Difference in LS Mean
Point estimate	-0.05
Confidence interval
level	95%
sides	2-sided
lower limit	-0.56
upper limit	0.46
Notes [231] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 48
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[232]
Method
Parameter type	Difference in LS Mean
Point estimate	-0.03
Confidence interval
level	95%
sides	2-sided
lower limit	-0.74
upper limit	0.69
Notes [232] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 52
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[233]
Method
Parameter type	Difference in LS Mean
Point estimate	0.2
Confidence interval
level	95%
sides	2-sided
lower limit	-0.91
upper limit	1.32
Notes [233] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.

Secondary: Change From Double-Blind Baseline in Number of Joints with Limited Range of Motion at DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52: Double-blind Phase Top of page

Secondary: Change From Open-Label Baseline in Physician Global Evaluation of Disease Activity at DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52: Double-blind Phase Top of page
End point title	Change From Open-Label Baseline in Physician Global Evaluation of Disease Activity at DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52: Double-blind Phase [234]
End point description	Physician global evaluation of disease activity was assessed on a VAS ranging from 0 to 10 mm, where 0=no activity and 10=maximum activity. DBFAS consisted of all randomised participants who received at least one dose of investigational product in the double-blind phase. Participants were reported under the treatment they were randomised. All participants reported under ‘Number of Participants Analysed’ contributed data to the table; however, may not have evaluable data for every row. Here “n” signifies number of participants evaluable for specified rows.
End point type	Secondary
End point timeframe	OL label Baseline (last value collected prior to Day 1 of tofacitinib administration in OL phase), DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Notes [234] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint is specific to Open-Label period hence Open-Label arms have been reported.
End point values Tofacitinib 5mg BID Double-Blind (DB) Placebo DB Number of subjects analysed 28 31 Units: Units on a scale least squares mean (standard error)     DB Week 4(n=27,31) -4.22 ( 0.33 ) -5.22 ( 0.32 )     DB Week 8 (n=25,25) -4.23 ( 0.32 ) -5.55 ( 0.32 )     DB Week 12(n=21,23) -4.89 ( 0.36 ) -5.42 ( 0.34 )     DB Week 16 (n=21,20) -4.96 ( 0.32 ) -5.22 ( 0.32 )     DB Week 20(n=19,15) -5.32 ( 0.23 ) -5.64 ( 0.24 )     DB Week 24 (n=18,15) -5.11 ( 0.22 ) -5.66 ( 0.23 )     DB Week 28 (n=17,12) -5.06 ( 0.37 ) -5.26 ( 0.40 )     DB Week 32 (n=13,10) -5.08 ( 0.26 ) -5.71 ( 0.28 )     DB Week 36 (n=13,10) -5.55 ( 0.16 ) -6.03 ( 0.18 )     DB Week 40 (n=11,9) -5.23 ( 0.30 ) -5.88 ( 0.33 )     DB Week 44(n=10, 9) -5.65 ( 0.21 ) -5.87 ( 0.22 )     DB Week 48(n=8, 5) -5.87 ( 0.18 ) -6.14 ( 0.24 )     DB Week 52 (n=6, 5) -5.86 ( 0.26 ) -5.97 ( 0.33 )
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 4
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[235]
Method
Parameter type	Difference in LS Mean
Point estimate	1.01
Confidence interval
level	95%
sides	2-sided
lower limit	0.09
upper limit	1.92
Notes [235] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Open-label baseline value, and Open-label baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 8
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[236]
Method
Parameter type	Difference in LS Mean
Point estimate	1.31
Confidence interval
level	95%
sides	2-sided
lower limit	0.4
upper limit	2.22
Notes [236] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Open-label baseline value, and Open-label baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 12
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[237]
Method
Parameter type	Difference in LS Mean
Point estimate	0.53
Confidence interval
level	95%
sides	2-sided
lower limit	-0.47
upper limit	1.53
Notes [237] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Open-label baseline value, and Open-label baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 16
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[238]
Method
Parameter type	Difference in LS Mean
Point estimate	0.26
Confidence interval
level	95%
sides	2-sided
lower limit	-0.63
upper limit	1.16
Notes [238] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Open-label baseline value, and Open-label baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 20
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[239]
Method
Parameter type	Difference in LS Mean
Point estimate	0.32
Confidence interval
level	95%
sides	2-sided
lower limit	-0.33
upper limit	0.97
Notes [239] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Open-label baseline value, and Open-label baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 24
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[240]
Method	Mixed Model for Repeated Measures
Parameter type	Difference in LS Mean
Point estimate	0.55
Confidence interval
level	95%
sides	2-sided
lower limit	-0.1
upper limit	1.2
Notes [240] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Open-label baseline value, and Open-label baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 28
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[241]
Method
Parameter type	Difference in LS Mean
Point estimate	0.2
Confidence interval
level	95%
sides	2-sided
lower limit	-0.93
upper limit	1.33
Notes [241] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Open-label baseline value, and Open-label baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 44
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[242]
Method
Parameter type	Difference in LS Mean
Point estimate	0.23
Confidence interval
level	95%
sides	2-sided
lower limit	-0.4
upper limit	0.85
Notes [242] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Open-label baseline value, and Open-label baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 32
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[243]
Method
Parameter type	Difference in LS Mean
Point estimate	0.62
Confidence interval
level	95%
sides	2-sided
lower limit	-0.17
upper limit	1.42
Notes [243] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Open-label baseline value, and Open-label baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 36
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[244]
Method
Parameter type	Difference in LS Mean
Point estimate	0.48
Confidence interval
level	95%
sides	2-sided
lower limit	-0.02
upper limit	0.98
Notes [244] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Open-label baseline value, and Open-label baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 40
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[245]
Method
Parameter type	Difference in LS Mean
Point estimate	0.64
Confidence interval
level	95%
sides	2-sided
lower limit	-0.3
upper limit	1.58
Notes [245] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Open-label baseline value, and Open-label baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 48
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[246]
Method
Parameter type	Difference in LS Mean
Point estimate	0.26
Confidence interval
level	95%
sides	2-sided
lower limit	-0.36
upper limit	0.88
Notes [246] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Open-label baseline value, and Open-label baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 52
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[247]
Method
Parameter type	Difference in LS Mean
Point estimate	0.11
Confidence interval
level	95%
sides	2-sided
lower limit	-0.87
upper limit	1.09
Notes [247] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Open-label baseline value, and Open-label baseline value by visit interaction.

Secondary: Change From Open-Label Baseline in Physician Global Evaluation of Disease Activity at DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52: Double-blind Phase Top of page

Secondary: Change From Double-Blind Baseline in Physician Global Evaluation of Disease Activity at DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52: Double-blind Phase Top of page
End point title	Change From Double-Blind Baseline in Physician Global Evaluation of Disease Activity at DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52: Double-blind Phase [248]
End point description	Physician global evaluation of disease activity was assessed on a VAS ranging from 0 to 10 mm, where 0=no activity and 10=maximum activity. DBFAS consisted of all randomised participants who received at least one dose of investigational product in the double-blind phase. Participants were reported under the treatment they were randomised. All participants reported under ‘Number of Participants Analysed’ contributed data to the table; however, may not have evaluable data for every row. Here “n” signifies number of participants evaluable for specified rows.
End point type	Secondary
End point timeframe	DB label Baseline (last value collected prior to Day 1 of tofacitinib administration in OL phase), DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Notes [248] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint is specific to Double-Blind period hence Double-Blind arms have been reported.
End point values Tofacitinib 5mg BID Double-Blind (DB) Placebo DB Number of subjects analysed 28 31 Units: Units on a scale least squares mean (standard error)     DB Week 4 (n=27,31) 0.16 ( 0.25 ) 0.21 ( 0.24 )     DB Week 8(n=25,25) 0.45 ( 0.32 ) -0.14 ( 0.32 )     DB Week 12 (n=21,23) 0.10 ( 0.40 ) -0.02 ( 0.39 )     DB Week 16(n=21,20) -0.11 ( 0.34 ) 0.15 ( 0.34 )     DB Week 20 (n=19,15) -0.51 ( 0.22 ) -0.35 ( 0.23 )     DB Week 24 (n=18,15) -0.32 ( 0.22 ) -0.37 ( 0.22 )     DB Week 28 (n=17,12) 0.09 ( 0.43 ) 0.19 ( 0.47 )     DB Week 32 (n=13,10) -0.11 ( 0.29 ) -0.42 ( 0.32 )     DB Week 36(n=13,10) -0.74 ( 0.17 ) -0.92 ( 0.18 )     DB Week 40 (n=11,9) -0.17 ( 0.35 ) -0.53 ( 0.37 )     DB Week 44 (n=10, 9) -0.79 ( 0.21 ) -0.70 ( 0.22 )     DB Week 48(n=8, 5) -1.03 ( 0.20 ) -1.09 ( 0.29 )     DB Week 52 (n=6, 5) -1.00 ( 0.27 ) -0.92 ( 0.39 )
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 8
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[249]
Method
Parameter type	Difference in LS Mean
Point estimate	0.58
Confidence interval
level	95%
sides	2-sided
lower limit	-0.37
upper limit	1.53
Notes [249] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 4
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[250]
Method
Parameter type	Difference in LS Mean
Point estimate	-0.05
Confidence interval
level	95%
sides	2-sided
lower limit	-0.77
upper limit	0.67
Notes [250] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 20
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[251]
Method
Parameter type	Difference in LS Mean
Point estimate	-0.16
Confidence interval
level	95%
sides	2-sided
lower limit	-0.83
upper limit	0.52
Notes [251] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 24
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[252]
Method
Parameter type	Difference in LS Mean
Point estimate	0.05
Confidence interval
level	95%
sides	2-sided
lower limit	-0.61
upper limit	0.71
Notes [252] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 52
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[253]
Method
Parameter type	Difference in LS Mean
Point estimate	-0.08
Confidence interval
level	95%
sides	2-sided
lower limit	-1.1
upper limit	0.94
Notes [253] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 32
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[254]
Method
Parameter type	Difference in LS Mean
Point estimate	0.31
Confidence interval
level	95%
sides	2-sided
lower limit	-0.61
upper limit	1.23
Notes [254] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 36
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[255]
Method
Parameter type	Difference in LS Mean
Point estimate	0.18
Confidence interval
level	95%
sides	2-sided
lower limit	-0.34
upper limit	0.71
Notes [255] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 40
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[256]
Method
Parameter type	Difference in LS Mean
Point estimate	0.36
Confidence interval
level	95%
sides	2-sided
lower limit	-0.74
upper limit	1.46
Notes [256] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 44
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[257]
Method
Parameter type	Difference in LS Mean
Point estimate	-0.09
Confidence interval
level	95%
sides	2-sided
lower limit	-0.75
upper limit	0.56
Notes [257] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 48
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[258]
Method
Parameter type	Difference in LS Mean
Point estimate	0.06
Confidence interval
level	95%
sides	2-sided
lower limit	-0.68
upper limit	0.81
Notes [258] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 16
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[259]
Method
Parameter type	Difference in LS Mean
Point estimate	-0.26
Confidence interval
level	95%
sides	2-sided
lower limit	-1.27
upper limit	0.74
Notes [259] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 12
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[260]
Method
Parameter type	Difference in LS Mean
Point estimate	0.12
Confidence interval
level	95%
sides	2-sided
lower limit	-1.06
upper limit	1.3
Notes [260] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 28
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[261]
Method
Parameter type	Difference in LS Mean
Point estimate	-0.1
Confidence interval
level	95%
sides	2-sided
lower limit	-1.45
upper limit	1.25
Notes [261] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.

Secondary: Change From Double-Blind Baseline in Physician Global Evaluation of Disease Activity at DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52: Double-blind Phase Top of page

Secondary: Change From Open-Label Baseline in ESR at DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52: Double-blind Phase Top of page
End point title	Change From Open-Label Baseline in ESR at DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52: Double-blind Phase [262]
End point description	DBFAS was used. All participants reported under ‘Number of Participants Analysed’ contributed data to the table; however, may not have evaluable data for every row. Here, “n” signifies number of participants evaluable for specified rows.
End point type	Secondary
End point timeframe	OL Baseline (last value collected prior to Day 1 of tofacitinib administration in OL phase), DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Notes [262] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint is specific to Open-Label period hence Open-Label arms have been reported.
End point values Tofacitinib 5mg BID Double-Blind (DB) Placebo DB Number of subjects analysed 28 31 Units: Millimeter per hour (mm/h) least squares mean (standard error)     DB Week 4 (n=27,31) -32.65 ( 4.72 ) -31.19 ( 4.49 )     DB Week 8(n=25,25) -36.55 ( 4.38 ) -29.32 ( 4.29 )     DB Week 12(n=21,23) -38.30 ( 4.50 ) -31.69 ( 4.35 )     DB Week 16(n=21,20) -39.52 ( 4.06 ) -31.02 ( 4.06 )     DB Week 20 (n=19,15) -41.82 ( 2.22 ) -37.86 ( 2.32 )     DB Week 24(n=18,15) -42.25 ( 2.25 ) -40.81 ( 2.33 )     DB Week 28 (n=17,12) -37.83 ( 4.07 ) -33.51 ( 4.39 )     DB Week 32 (n=13,10) -37.90 ( 3.67 ) -35.04 ( 3.91 )     DB Week 36 (n=13,10) -39.36 ( 4.49 ) -28.41 ( 4.79 )     DB Week 40(n=11,9) -39.98 ( 4.12 ) -35.70 ( 4.31 )     DB Week 44 (n=10, 9) -47.16 ( 2.28 ) -38.84 ( 2.34 )     DB Week 48 (n=8, 5) -47.16 ( 2.29 ) -42.32 ( 2.72 )     DB Week 52 (n=6, 4) -51.46 ( 1.08 ) -50.12 ( 1.24 )
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 8
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[263]
Method
Parameter type	Difference in LS Mean
Point estimate	-7.22
Confidence interval
level	95%
sides	2-sided
lower limit	-19.62
upper limit	5.17
Notes [263] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Open label baseline value, and Open-label baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 4
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[264]
Method
Parameter type	Difference in LS Mean
Point estimate	-1.46
Confidence interval
level	95%
sides	2-sided
lower limit	-14.59
upper limit	11.66
Notes [264] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Open label baseline value, and Open-label baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 16
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[265]
Method
Parameter type	Difference in LS Mean
Point estimate	-8.5
Confidence interval
level	95%
sides	2-sided
lower limit	-20.28
upper limit	3.27
Notes [265] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Open label baseline value, and Open-label baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 28
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[266]
Method
Parameter type	Difference in LS Mean
Point estimate	-4.32
Confidence interval
level	95%
sides	2-sided
lower limit	-16.67
upper limit	8.03
Notes [266] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Open label baseline value, and Open-label baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 24
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[267]
Method
Parameter type	Difference in LS Mean
Point estimate	-1.44
Confidence interval
level	95%
sides	2-sided
lower limit	-8.09
upper limit	5.21
Notes [267] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Open label baseline value, and Open-label baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 20
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[268]
Method
Parameter type	Difference in LS Mean
Point estimate	-3.95
Confidence interval
level	95%
sides	2-sided
lower limit	-10.53
upper limit	2.62
Notes [268] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Open label baseline value, and Open-label baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 12
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[269]
Method
Parameter type	Difference in LS Mean
Point estimate	-6.61
Confidence interval
level	95%
sides	2-sided
lower limit	-19.36
upper limit	6.14
Notes [269] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Open label baseline value, and Open-label baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 52
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[270]
Method
Parameter type	Difference in LS Mean
Point estimate	-1.34
Confidence interval
level	95%
sides	2-sided
lower limit	-5.16
upper limit	2.48
Notes [270] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Open label baseline value, and Open-label baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 48
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[271]
Method
Parameter type	Difference in LS Mean
Point estimate	-4.84
Confidence interval
level	95%
sides	2-sided
lower limit	-12.6
upper limit	2.92
Notes [271] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Open label baseline value, and Open-label baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 44
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[272]
Method
Parameter type	Difference in LS Mean
Point estimate	-8.32
Confidence interval
level	95%
sides	2-sided
lower limit	-15.2
upper limit	-1.43
Notes [272] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Open label baseline value, and Open-label baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 36
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[273]
Method
Parameter type	Difference in LS Mean
Point estimate	-10.95
Confidence interval
level	95%
sides	2-sided
lower limit	-24.63
upper limit	2.73
Notes [273] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Open label baseline value, and Open-label baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 32
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[274]
Method
Parameter type	Difference in LS Mean
Point estimate	-2.86
Confidence interval
level	95%
sides	2-sided
lower limit	-13.97
upper limit	8.25
Notes [274] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Open label baseline value, and Open-label baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 40
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[275]
Method
Parameter type	Difference in LS Mean
Point estimate	-4.28
Confidence interval
level	95%
sides	2-sided
lower limit	-16.74
upper limit	8.18
Notes [275] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Open label baseline value, and Open-label baseline value by visit interaction.

Secondary: Change From Open-Label Baseline in ESR at DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52: Double-blind Phase Top of page

Secondary: Change From Double-Blind Baseline in ESR at DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52: Double-blind Phase Top of page
End point title	Change From Double-Blind Baseline in ESR at DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52: Double-blind Phase [276]
End point description	DBFAS set was used. All participants reported under ‘Number of Participants Analysed’ contributed data to the table; however, may not have evaluable data for every row. Here, “n” signifies number of participants evaluable for specified rows.
End point type	Secondary
End point timeframe	DB Baseline (values at randomization), DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Notes [276] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint is specific to Double-Blind period hence Double-Blind arms have been reported.
End point values Tofacitinib 5mg BID Double-Blind (DB) Placebo DB Number of subjects analysed 28 31 Units: Millimeter/ hour (mm/h) least squares mean (standard error)     DB Week 4 (n=27,30) 3.35 ( 3.71 ) 9.41 ( 3.50 )     DB Week 8 (n=25,24) 1.94 ( 3.97 ) 12.39 ( 3.93 )     DB Week 12 (n=21,22) 1.42 ( 4.53 ) 12.28 ( 4.40 )     DB Week 16(n=21,19) 0.45 ( 4.32 ) 13.59 ( 4.35 )     DB Week 20(n=19,14) -2.04 ( 2.17 ) 4.98 ( 2.31 )     DB Week 24(n=18,14) -2.51 ( 2.14 ) 2.01 ( 2.28 )     DB Week 28(n=17,12) 1.73 ( 4.19 ) 11.08 ( 4.55 )     DB Week 32(n=13,10) 2.01 ( 3.78 ) 8.77 ( 4.05 )     DB Week 36(n=13,10) 0.88 ( 4.83 ) 16.37 ( 5.17 )     DB Week 40(n=11,9) 0.34 ( 4.25 ) 8.33 ( 4.47 )     DB Week 44(n=10,9) -7.05 ( 2.34 ) 3.44 ( 2.41 )     DB Week 48(n=8,5) -8.07 ( 2.38 ) -2.14 ( 2.96 )     DB Week 52(n=6,4) -11.70 ( 1.39 ) -9.14 ( 1.73 )
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 40
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[277]
Method
Parameter type	Difference in LS Mean
Point estimate	-7.99
Confidence interval
level	95%
sides	2-sided
lower limit	-21
upper limit	5.03
Notes [277] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 4
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[278]
Method
Parameter type	Difference in LS Mean
Point estimate	-6.05
Confidence interval
level	95%
sides	2-sided
lower limit	-16.3
upper limit	4.19
Notes [278] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 8
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[279]
Method
Parameter type	Difference in LS Mean
Point estimate	-10.46
Confidence interval
level	95%
sides	2-sided
lower limit	-21.68
upper limit	0.77
Notes [279] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 12
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[280]
Method
Parameter type	Difference in LS Mean
Point estimate	-10.86
Confidence interval
level	95%
sides	2-sided
lower limit	-23.75
upper limit	2.03
Notes [280] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 16
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[281]
Method
Parameter type	Difference in LS Mean
Point estimate	-13.15
Confidence interval
level	95%
sides	2-sided
lower limit	-25.83
upper limit	-0.46
Notes [281] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 20
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[282]
Method
Parameter type	Difference in LS Mean
Point estimate	-7.02
Confidence interval
level	95%
sides	2-sided
lower limit	-13.56
upper limit	-0.47
Notes [282] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 24
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[283]
Method
Parameter type	Difference in LS Mean
Point estimate	-4.53
Confidence interval
level	95%
sides	2-sided
lower limit	-11
upper limit	1.95
Notes [283] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 28
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[284]
Method
Parameter type	Difference in LS Mean
Point estimate	-9.35
Confidence interval
level	95%
sides	2-sided
lower limit	-22.24
upper limit	3.54
Notes [284] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 32
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[285]
Method
Parameter type	Difference in LS Mean
Point estimate	-6.75
Confidence interval
level	95%
sides	2-sided
lower limit	-18.34
upper limit	4.83
Notes [285] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 36
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[286]
Method
Parameter type	Difference in LS Mean
Point estimate	-15.49
Confidence interval
level	95%
sides	2-sided
lower limit	-30.36
upper limit	-0.63
Notes [286] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 44
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[287]
Method
Parameter type	Difference in LS Mean
Point estimate	-10.49
Confidence interval
level	95%
sides	2-sided
lower limit	-17.67
upper limit	-3.31
Notes [287] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 48
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[288]
Method
Parameter type	Difference in LS Mean
Point estimate	-5.93
Confidence interval
level	95%
sides	2-sided
lower limit	-13.53
upper limit	1.67
Notes [288] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 52
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[289]
Method
Parameter type	Difference in LS Mean
Point estimate	-2.57
Confidence interval
level	95%
sides	2-sided
lower limit	-6.37
upper limit	1.24
Notes [289] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.

Secondary: Change From Double-Blind Baseline in ESR at DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52: Double-blind Phase Top of page

Secondary: Change From Open-Label Baseline in CHAQ -Parental Evaluation of Overall Well-being at DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52: Double-blind Phase Top of page
End point title	Change From Open-Label Baseline in CHAQ -Parental Evaluation of Overall Well-being at DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52: Double-blind Phase [290]
End point description	The CHAQ, derived from the adult health assessment questionnaire, comprised of two indices disability and discomfort, and parent global assessment of overall well-being. For assessment of overall well-being, the parent/legal guardian/participant were required to rate the overall well-being by entering a number from 0 to 10 (in 0.5 increments), on a 21-circle VAS where ‘0’= Very Well’ and ‘10=Very Poorly. DBFAS set was used. All participants reported under ‘Number of Participants Analysed’ contributed data to the table; however, may not have evaluable data for every row. Here “n” signifies number of participants evaluable for specified rows.
End point type	Secondary
End point timeframe	OL label Baseline (last value collected prior to Day 1 of tofacitinib administration in OL phase), DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Notes [290] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint is specific to Double-Blind period hence Double-Blind arms have been reported.
End point values Tofacitinib 5mg BID Double-Blind (DB) Placebo DB Number of subjects analysed 28 31 Units: Units on a scale least squares mean (standard error)     DB Week 4 (n-27,30) -4.31 ( 0.37 ) -5.52 ( 0.34 )     DB Week 8 (n=25,25) -4.56 ( 0.36 ) -5.38 ( 0.35 )     DB Week 12(n=21,23) -4.97 ( 0.34 ) -5.28 ( 0.33 )     DB Week 16(n=21,20) -4.88 ( 0.29 ) -5.46 ( 0.29 )     DB Week 20 (n=19,15) -5.19 ( 0.32 ) -5.36 ( 0.34 )     DB Week 24 (n=18,15) -4.97 ( 0.29 ) -5.62 ( 0.30 )     DB Week 28(n=17,12) -5.08 ( 0.44 ) -5.00 ( 0.48 )     DB Week 32 (n=13,10) -5.63 ( 0.18 ) -5.55 ( 0.20 )     DB Week 36 (n=13,10) -5.81 ( 0.18 ) -5.87 ( 0.21 )     DB Week 40 (n=11,9) -5.98 ( 0.16 ) -5.94 ( 0.18 )     DB Week 44 (n=10, 9) -5.95 ( 0.21 ) -5.79 ( 0.23 )     DB Week 48 (n=8, 5) -5.45 ( 0.31 ) -5.30 ( 0.57 )     DB Week 52 (n=6, 5) -6.06 ( 0.25 ) -5.98 ( 0.43 )
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 24
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[291]
Method
Parameter type	Difference in LS Mean
Point estimate	0.66
Confidence interval
level	95%
sides	2-sided
lower limit	-0.18
upper limit	1.49
Notes [291] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Open-Label baseline value, and Open-Label baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 20
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[292]
Method
Parameter type	Difference in LS Mean
Point estimate	0.16
Confidence interval
level	95%
sides	2-sided
lower limit	-0.78
upper limit	1.1
Notes [292] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Open-Label baseline value, and Open-Label baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 16
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[293]
Method
Parameter type	Difference in LS Mean
Point estimate	0.57
Confidence interval
level	95%
sides	2-sided
lower limit	-0.26
upper limit	1.41
Notes [293] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Open-Label baseline value, and Open-Label baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 12
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[294]
Method
Parameter type	Difference in LS Mean
Point estimate	0.31
Confidence interval
level	95%
sides	2-sided
lower limit	-0.65
upper limit	1.27
Notes [294] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Open-Label baseline value, and Open-Label baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 8
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[295]
Method
Parameter type	Difference in LS Mean
Point estimate	0.82
Confidence interval
level	95%
sides	2-sided
lower limit	-0.2
upper limit	1.85
Notes [295] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Open-Label baseline value, and Open-Label baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 4
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[296]
Method
Parameter type	Difference in LS Mean
Point estimate	0.51
Confidence interval
level	95%
sides	2-sided
lower limit	0.2
upper limit	2.22
Notes [296] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Open-Label baseline value, and Open-Label baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 48
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[297]
Method
Parameter type	Difference in LS Mean
Point estimate	-0.14
Confidence interval
level	95%
sides	2-sided
lower limit	-1.51
upper limit	1.22
Notes [297] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Open-Label baseline value, and Open-Label baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 44
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[298]
Method
Parameter type	Difference in LS Mean
Point estimate	-0.16
Confidence interval
level	95%
sides	2-sided
lower limit	-0.82
upper limit	0.5
Notes [298] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Open-Label baseline value, and Open-Label baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 40
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[299]
Method
Parameter type	Difference in LS Mean
Point estimate	-0.04
Confidence interval
level	95%
sides	2-sided
lower limit	-0.55
upper limit	0.47
Notes [299] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Open-Label baseline value, and Open-Label baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 36
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[300]
Method
Parameter type	Difference in LS Mean
Point estimate	0.06
Confidence interval
level	95%
sides	2-sided
lower limit	-0.51
upper limit	0.63
Notes [300] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Open-Label baseline value, and Open-Label baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 32
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[301]
Method
Parameter type	Difference in LS Mean
Point estimate	-0.07
Confidence interval
level	95%
sides	2-sided
lower limit	-0.65
upper limit	0.5
Notes [301] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Open-Label baseline value, and Open-Label baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 52
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[302]
Method
Parameter type	Difference in LS Mean
Point estimate	-0.08
Confidence interval
level	95%
sides	2-sided
lower limit	-1.05
upper limit	0.88
Notes [302] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Open-Label baseline value, and Open-Label baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 28
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[303]
Method
Parameter type	Difference in LS Mean
Point estimate	-0.08
Confidence interval
level	95%
sides	2-sided
lower limit	-1.43
upper limit	1.27
Notes [303] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Open-Label baseline value, and Open-Label baseline value by visit interaction.

Secondary: Change From Open-Label Baseline in CHAQ -Parental Evaluation of Overall Well-being at DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52: Double-blind Phase Top of page

Secondary: Change From Double-Blind Baseline in CHAQ -Parental Evaluation of Overall Well-being at DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52: Double-blind Phase Top of page
End point title	Change From Double-Blind Baseline in CHAQ -Parental Evaluation of Overall Well-being at DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52: Double-blind Phase [304]
End point description	The CHAQ, derived from the adult health assessment questionnaire, comprised of two indices disability and discomfort, and parent global assessment of overall well-being. For assessment of overall well-being, the parent/legal guardian/participant were required to rate the overall well-being by entering a number from 0 to 10 (in 0.5 increments), on a 21-circle VAS where ‘0’= Very Well’ and ‘10=Very Poorly. DBFAS set was used. All participants reported under ‘Number of Participants Analysed’ contributed data to the table; however, may not have evaluable data for every row. Here “n” signifies number of participants evaluable for specified rows.
End point type	Secondary
End point timeframe	DB Baseline (value at randomization), DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Notes [304] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint is specific to Double-Blind period hence Double-Blind arms have been reported.
End point values Tofacitinib 5mg BID Double-Blind (DB) Placebo DB Number of subjects analysed 28 31 Units: Units on a scale least squares mean (standard error)     DB Week 4 (n=27,30) 0.46 ( 0.28 ) -0.03 ( 0.27 )     DB Week 8 (n=25,25) 0.60 ( 0.38 ) 0.12 ( 0.38 )     DB Week 12 (n=21,23) 0.25 ( 0.36 ) 0.22 ( 0.35 )     DB Week 16 (n=21,20) 0.27 ( 0.31 ) 0.04 ( 0.31 )     DB Week 20 (n=19,15) 0.14 ( 0.37 ) 0.05 ( 0.38 )     DB Week 24 (n=18,15) 0.14 ( 0.29 ) -0.14 ( 0.30 )     DB Week 28 (n=17,12) 0.54 ( 0.52 ) 0.52 ( 0.56 )     DB Week 32 (n=13,10) -0.32 ( 0.24 ) -0.34 ( 0.25 )     DB Week 36 (n=13,10) -0.56 ( 0.21 ) -0.63 ( 0.22 )     DB Week 40 (n=11,9) -0.72 ( 0.19 ) -0.78 ( 0.20 )     DB Week 44 (n=10,9) -0.65 ( 0.24 ) -0.54 ( 0.25 )     DB Week 48 (n=8,5) -0.16 ( 0.36 ) -0.37 ( 0.53 )     DB Week 52 (n=6,5) -0.82 ( 0.26 ) -0.87 ( 0.38 )
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 4
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[305]
Method
Parameter type	Difference in LS Mean
Point estimate	0.49
Confidence interval
level	95%
sides	2-sided
lower limit	-0.32
upper limit	1.3
Notes [305] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 8
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[306]
Method
Parameter type	Difference in LS Mean
Point estimate	0.48
Confidence interval
level	95%
sides	2-sided
lower limit	-0.64
upper limit	1.61
Notes [306] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 12
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[307]
Method
Parameter type	Difference in LS Mean
Point estimate	0.03
Confidence interval
level	95%
sides	2-sided
lower limit	-1.02
upper limit	1.07
Notes [307] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 16
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[308]
Method
Parameter type	Difference in LS Mean
Point estimate	0.23
Confidence interval
level	95%
sides	2-sided
lower limit	-0.69
upper limit	1.14
Notes [308] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 20
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[309]
Method
Parameter type	Difference in LS Mean
Point estimate	0.09
Confidence interval
level	95%
sides	2-sided
lower limit	-1.05
upper limit	1.22
Notes [309] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 24
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[310]
Method
Parameter type	Difference in LS Mean
Point estimate	0.28
Confidence interval
level	95%
sides	2-sided
lower limit	-0.6
upper limit	1.16
Notes [310] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 28
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[311]
Method
Parameter type	Difference in LS Mean
Point estimate	0.02
Confidence interval
level	95%
sides	2-sided
lower limit	-1.6
upper limit	1.64
Notes [311] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 36
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[312]
Method
Parameter type	Difference in LS Mean
Point estimate	0.07
Confidence interval
level	95%
sides	2-sided
lower limit	-0.58
upper limit	0.73
Notes [312] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 32
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[313]
Method
Parameter type	Difference in LS Mean
Point estimate	0.02
Confidence interval
level	95%
sides	2-sided
lower limit	-1.6
upper limit	1.64
Notes [313] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 40
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[314]
Method
Parameter type	Difference in LS Mean
Point estimate	0.06
Confidence interval
level	95%
sides	2-sided
lower limit	-0.53
upper limit	0.65
Notes [314] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 48
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[315]
Method
Parameter type	Difference in LS Mean
Point estimate	0.21
Confidence interval
level	95%
sides	2-sided
lower limit	-1.13
upper limit	1.54
Notes [315] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 44
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[316]
Method
Parameter type	Difference in LS Mean
Point estimate	-0.12
Confidence interval
level	95%
sides	2-sided
lower limit	-0.87
upper limit	0.64
Notes [316] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 52
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[317]
Method
Parameter type	Difference in LS Mean
Point estimate	0.05
Confidence interval
level	95%
sides	2-sided
lower limit	-1
upper limit	1.11
Notes [317] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.

Secondary: Change From Double-Blind Baseline in CHAQ -Parental Evaluation of Overall Well-being at DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52: Double-blind Phase Top of page

Secondary: Change From Open-Label Baseline in Child Health Questionnaire (CHQ) Responses at End of Open-label Phase Part 1 Top of page
End point title	Change From Open-Label Baseline in Child Health Questionnaire (CHQ) Responses at End of Open-label Phase Part 1 [318]
End point description	The CHQ is a validated general pediatric quality of life instrument. The CHQ assessed for 14 physical and psychosocial domains: general health perceptions, physical functioning, role/social physical functioning, bodily pain, role/social emotional functioning, role/social behavioral functioning, parent/legal guardian/adult caregiver impact-time, parent/legal guardian/adult caregiver impact-emotional, self-esteem, mental health, behavior, family activities, family cohesion, and change in health. The response options for the CHQ are ordinal scales that vary by the item. Each item consisted of 4–6 response options.The CHQ score was determined based on the parent/legal guardian/adult caregiver’s questionnaire responses. OLPT1 analysis set was used. All participants reported under Number of subjects analysed” contributed data to the table; however, may not have evaluable data for every row. Here, “n” signifies number of participants evaluable for specified rows.
End point type	Secondary
End point timeframe	OL Baseline up to 16 weeks
Notes [318] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint is specific to Open-Label period hence Open-Label arms have been reported.
End point values Tofacitinib 5mg BID Open_Label (OL) Part 1 Number of subjects analysed 100 Units: Units on a scale arithmetic mean (standard deviation)     Global Health Subscale Standardized Score n=85 26.12 ( 29.10 )     Physical Functioning Standardized Score n=85 28.95 ( 33.79 )     Social Limitations: Emotional Score n=84 27.51 ( 38.39 )     Social Limitations: Physical Score n=84 31.15 ( 42.96 )     Bodily Pain Subscale Standardized Score n=85 32.00 ( 26.67 )     Behavior Subscale Standardized Score n=85 10.98 ( 17.14 )     Global Behavior Subscale Standardized Score n=85 11.18 ( 27.75 )     Mental Health Subscale Standardized Score n=84 13.33 ( 20.20 )     Self Esteem Subscale Standardized Score n=83 7.68 ( 21.29 )     General Health Subscale Score n=85 8.37 ( 13.93 )     Change in Health Subscale Score n=85 1.28 ( 1.10 )     Emotional Impact on Parent Subscale Score n=85 12.75 ( 26.43 )     Time Impact on Parent Standardized Score n=84 14.81 ( 28.62 )     Family Activities Standardized Score n=84 74.03 ( 22.41 )     Family Cohesion Standardized Score n=84 8.10 ( 22.67 )
No statistical analyses for this end point

Secondary: Change From Open-Label Baseline in Child Health Questionnaire (CHQ) Responses at End of Open-label Phase Part 1 Top of page

Secondary: Change From Open-Label Baseline in CHQ Responses at End of Open-label Phase Part 2 Top of page
End point title	Change From Open-Label Baseline in CHQ Responses at End of Open-label Phase Part 2 [319]
End point description	The CHQ is a validated general pediatric quality of life instrument. The CHQ assessed for 14 physical and psychosocial domains: general health perceptions, physical functioning, role/social physical functioning, bodily pain, role/social emotional functioning, role/social behavioral functioning, parent/legal guardian/adult caregiver impact-time, parent/legal guardian/adult caregiver impact-emotional, self-esteem, mental health, behavior, family activities, family cohesion, and change in health. The response options for the CHQ are ordinal scales that vary by the item. Each item consisted of 4–6 response options. The CHQ score was determined based on the parent/legal guardian/adult caregiver’s questionnaire responses. OLPT2 analysis set was used. “Number of subjects analysed” =participants evaluable for the endpoint and “n” =number of participants evaluable for specified rows.
End point type	Secondary
End point timeframe	Baseline (last value collected prior to Day 1 of tofacitinib administration in OL phase) up to 24 weeks
Notes [319] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint is specific to Open-Label period hence Open-Label arms have been reported.
End point values Tofacitinib 5mg BID OL Part 2 Number of subjects analysed 29 Units: Units on a scale arithmetic mean (standard deviation)     Global Health Standardized Score n=29 25.52 ( 35.46 )     Physical Functioning Standardized Score n=29 33.33 ( 31.29 )     Social Limitations: Emotional Score n=28 28.17 ( 43.98 )     Social Limitations: Physical Score n=28 38.10 ( 42.28 )     Bodily Pain Standardized Score n=29 34.48 ( 26.80 )     Behavior Standardized Score n=29 13.02 ( 21.14 )     Global Behavior Standardized Score n=29 10.00 ( 34.10 )     Mental Health Standardized Score n=28 18.04 ( 21.01 )     Self Esteem Standardized Score n=27 8.30 ( 34.18 )     General Health Standardized Score n=28 8.18 ( 15.94 )     Change in Health Subscale Score n=28 1.54 ( 1.23 )     Emotional Impact on Parent Standardized Score n=28 22.92 ( 36.33 )     Time Impact on Parent Standardized Score n=27 34.57 ( 25.66 )     Family Activities Standardized Score n=27 27.62 ( 25.87 )     Family Cohesion Standardized Score n=27 10.00 ( 23.25 )
No statistical analyses for this end point

Secondary: Change From Open-Label Baseline in CHQ Responses at End of Open-label Phase Part 2 Top of page

Secondary: Change From Double-Blind Baseline in CHQ Responses at DB Weeks 24, 48: Double-Blind Phase Top of page
End point title	Change From Double-Blind Baseline in CHQ Responses at DB Weeks 24, 48: Double-Blind Phase [320]
End point description	The CHQ is a validated general pediatric quality of life instrument. The CHQ assessed for 14 physical and psychosocial domains: general health perceptions, physical functioning, role/social physical functioning, bodily pain, role/social emotional functioning, role/social behavioral functioning, parent/legal guardian/adult caregiver impact-time, parent/legal guardian/adult caregiver impact-emotional, self-esteem, mental health, behavior, family activities, family cohesion, and change in health. The response options for the CHQ are ordinal scales that vary by the item. Each item consisted of 4–6 response options. The CHQ score was determined based on the parent/legal guardian/adult caregiver’s questionnaire responses. DBFAS analysis set was used. “Number of subjects analysed” =participants evaluable for the endpoint and “n” =number of participants evaluable for specified rows.
End point type	Secondary
End point timeframe	DB Baseline (values at randomization), DB Weeks 24, 48
Notes [320] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint is specific to Double-Blind period hence Double-Blind arms have been reported.
End point values Tofacitinib 5mg BID Double-Blind (DB) Placebo DB Number of subjects analysed 17 15 Units: Units on a scale least squares mean (standard error)     Global Health Score:Week 24 n= (17,15) 4.02 ( 4.71 ) -1.98 ( 5.02 )     Global Health Score:Week 48 n= (5,4) 4.09 ( 3.93 ) 1.24 ( 4.49 )     Physical Functioning Score:Week 24 n=(17,15) 2.51 ( 3.86 ) 6.70 ( 3.99 )     Physical Functioning Score:Week 48 n=(5,4) 5.24 ( 9.13 ) 2.93 ( 14.02 )     Social Limitation:Emotional Score:Week24 n=(17,15) 2.62 ( 4.00 ) 8.09 ( 4.18 )     Social Limitation:Emotional Score:Week48 n=(5,4) 6.09 ( 7.69 ) -0.73 ( 10.33 )     Social Limitations:Physical Score:Week24 n=(17,15) 2.75 ( 4.27 ) 8.98 ( 4.54 )     Social Limitations:Physical Score:Week48 n=(5,4) 3.45 ( 13.33 ) -7.64 ( 20.06 )     Bodily Pain Score:Week 24 n=(17,15) -1.61 ( 4.19 ) -0.16 ( 4.41 )     Bodily Pain Score:Week 48 n=(5,4) -2.72 ( 10.19 ) -19.92 ( 13.98 )     Behavior Score:Week 24 n=(17,15) 2.33 ( 2.68 ) 7.48 ( 2.87 )     Behavior Score:Week 48 n=(5,4) -4.50 ( 4.97 ) 10.53 ( 5.35 )     Global Behavior Score:Week 24 n=(17,15) 4.17 ( 3.89 ) 9.48 ( 4.13 )     Global Behavior Score:Week48 n=(5,4) 5.90 ( 4.00 ) 13.14 ( 4.54 )     Mental Health Score:Week 24 n=(17,15) 6.59 ( 3.56 ) 2.14 ( 3.78 )     Mental Health Score:Week48 n=(5,4) 0.79 ( 4.98 ) 8.26 ( 5.71 )     Self Esteem Score:Week 24 n= (17,15) 6.68 ( 3.05 ) 6.69 ( 3.24 )     Self Esteem Score:Week 48 n=(5,4) 3.05 ( 7.24 ) 10.64 ( 8.04 )     General Health Score:Week 24 n=(17,15) 5.02 ( 3.21 ) 0.03 ( 3.42 )     General Health Score:Week 48 n=(5,4) 9.59 ( 5.20 ) 10.60 ( 5.92 )     Change in Health Score:Week 24 n=(17,15) 0.45 ( 0.12 ) 0.48 ( 0.13 )     Change in Health Score:Week48 n=(5,4) 0.64 ( 0.32 ) 0.16 ( 0.35 )     Emotional Impact on Parent Score:Week 24 n=(17,15) 15.00 ( 4.28 ) 12.75 ( 4.53 )     Emotional Impact on Parent Score:Week 48 n=(5,4) 7.15 ( 10.25 ) 32.22 ( 11.79 )     Time Impact on Parent Score Week 24 n=(17,15) 7.53 ( 5.10 ) 5.66 ( 5.25 )     Time Impact on Parent Score Week 48 n=(5,4) 11.60 ( 8.94 ) 20.79 ( 14.05 )     Family Activities Score:Week 24 n=(17,15) 5.71 ( 2.96 ) 9.68 ( 3.13 )     Family Activities Score:Week 48 n=(5,4) 6.65 ( 5.73 ) 15.95 ( 7.16 )     Family Cohesion Score:Week 24 n=(17,15) 2.84 ( 3.71 ) 6.36 ( 3.96 )     Family Cohesion Score:Week 48 n=(5,4) -12.24 ( 13.08 ) 8.18 ( 15.58 )
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	Physical Subscale score: DB Week 24
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	32
Analysis specification	Pre-specified
Analysis type	[321]
Method
Parameter type	Difference in LS Mean
Point estimate	-6.22
Confidence interval
level	95%
sides	2-sided
lower limit	-18.95
upper limit	6.5
Notes [321] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	Emotional Subscale score:DB Week 48
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	32
Analysis specification	Pre-specified
Analysis type	[322]
Method
Parameter type	Difference in LS Mean
Point estimate	6.82
Confidence interval
level	95%
sides	2-sided
lower limit	-20.92
upper limit	34.57
Notes [322] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	Emotional Subscale score:DB Week 24
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	32
Analysis specification	Pre-specified
Analysis type	[323]
Method
Parameter type	Difference in LS Mean
Point estimate	-5.47
Confidence interval
level	95%
sides	2-sided
lower limit	-17.37
upper limit	6.43
Notes [323] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	Physical Functioning Score: DB Week 48
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	32
Analysis specification	Pre-specified
Analysis type	[324]
Method
Parameter type	Difference in LS Mean
Point estimate	2.31
Confidence interval
level	95%
sides	2-sided
lower limit	-37.06
upper limit	41.68
Notes [324] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	Physical Functioning Score: DB Week 24
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	32
Analysis specification	Pre-specified
Analysis type	[325]
Method
Parameter type	Difference in LS Mean
Point estimate	-4.19
Confidence interval
level	95%
sides	2-sided
lower limit	-15.78
upper limit	7.4
Notes [325] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	Global Health Score: DB Week 48
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	32
Analysis specification	Pre-specified
Analysis type	[326]
Method
Parameter type	Difference in LS Mean
Point estimate	2.85
Confidence interval
level	95%
sides	2-sided
lower limit	-12.43
upper limit	18.14
Notes [326] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	Global Health Score: DB Week 24
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	32
Analysis specification	Pre-specified
Analysis type	[327]
Method
Parameter type	Difference in LS Mean
Point estimate	6
Confidence interval
level	95%
sides	2-sided
lower limit	-8.35
upper limit	20.36
Notes [327] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	Global Behavior score:DB Week 48
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	32
Analysis specification	Pre-specified
Analysis type	[328]
Method
Parameter type	Difference in LS Mean
Point estimate	-7.24
Confidence interval
level	95%
sides	2-sided
lower limit	-20.35
upper limit	5.87
Notes [328] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	Global Behavior score:DB Week 24
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	32
Analysis specification	Pre-specified
Analysis type	[329]
Method
Parameter type	Difference in LS Mean
Point estimate	-5.32
Confidence interval
level	95%
sides	2-sided
lower limit	-16.92
upper limit	6.29
Notes [329] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	Behavior Subscale score:DB Week 48
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	32
Analysis specification	Pre-specified
Analysis type	[330]
Method
Parameter type	Difference in LS Mean
Point estimate	-15.03
Confidence interval
level	95%
sides	2-sided
lower limit	-33.12
upper limit	3.06
Notes [330] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	Behavior Subscale score:DB Week 24
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	32
Analysis specification	Pre-specified
Analysis type	[331]
Method
Parameter type	Difference in LS Mean
Point estimate	-5.15
Confidence interval
level	95%
sides	2-sided
lower limit	-13.24
upper limit	2.93
Notes [331] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	Bodily Pain Subscale score: DB Week 48
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	32
Analysis specification	Pre-specified
Analysis type	[332]
Method
Parameter type	Difference in LS Mean
Point estimate	17.2
Confidence interval
level	95%
sides	2-sided
lower limit	-28.01
upper limit	62.41
Notes [332] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	Bodily Pain Subscale score: DB Week 24
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	32
Analysis specification	Pre-specified
Analysis type	[333]
Method
Parameter type	Difference in LS Mean
Point estimate	-1.45
Confidence interval
level	95%
sides	2-sided
lower limit	-13.97
upper limit	11.06
Notes [333] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	Physical Subscale score: DB Week 48
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	32
Analysis specification	Pre-specified
Analysis type	[334]
Method
Parameter type	Difference in LS Mean
Point estimate	11.09
Confidence interval
level	95%
sides	2-sided
lower limit	-46.24
upper limit	68.42
Notes [334] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	Mental Health score: DB Week 24
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	32
Analysis specification	Pre-specified
Analysis type	[335]
Method
Parameter type	Difference in LS Mean
Point estimate	4.44
Confidence interval
level	95%
sides	2-sided
lower limit	-6.18
upper limit	15.07
Notes [335] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	General Health Subscale score:DB Week 24
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	32
Analysis specification	Pre-specified
Analysis type	[336]
Method
Parameter type	Difference in LS Mean
Point estimate	4.98
Confidence interval
level	95%
sides	2-sided
lower limit	-4.81
upper limit	14.77
Notes [336] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	Self Esteem Subscale score: DB Week 48
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	32
Analysis specification	Pre-specified
Analysis type	[337]
Method
Parameter type	Difference in LS Mean
Point estimate	-7.59
Confidence interval
level	95%
sides	2-sided
lower limit	-33.87
upper limit	18.7
Notes [337] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	Self Esteem Subscale score: DB Week 24
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	32
Analysis specification	Pre-specified
Analysis type	[338]
Method
Parameter type	Difference in LS Mean
Point estimate	-0.01
Confidence interval
level	95%
sides	2-sided
lower limit	-9.14
upper limit	9.13
Notes [338] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	Mental Health score: DB Week 48
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	32
Analysis specification	Pre-specified
Analysis type	[339]
Method
Parameter type	Difference in LS Mean
Point estimate	-7.46
Confidence interval
level	95%
sides	2-sided
lower limit	-24.37
upper limit	9.45
Notes [339] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	General Health Subscale score:DB Week 48
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	32
Analysis specification	Pre-specified
Analysis type	[340]
Method
Parameter type	Difference in LS Mean
Point estimate	-1.02
Confidence interval
level	95%
sides	2-sided
lower limit	-20.31
upper limit	18.28
Notes [340] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	Health Subscale Score: DB Week 24
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	32
Analysis specification	Pre-specified
Analysis type	[341]
Method
Parameter type	Difference in LS Mean
Point estimate	-0.03
Confidence interval
level	95%
sides	2-sided
lower limit	-0.4
upper limit	0.33
Notes [341] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	Health Subscale Score: DB Week 48
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	32
Analysis specification	Pre-specified
Analysis type	[342]
Method
Parameter type	Difference in LS Mean
Point estimate	0.48
Confidence interval
level	95%
sides	2-sided
lower limit	-0.68
upper limit	1.65
Notes [342] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	Emotional Impact on Parent Subscale score: DB Week 24
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	32
Analysis specification	Pre-specified
Analysis type	[343]
Method
Parameter type	Difference in LS Mean
Point estimate	2.25
Confidence interval
level	95%
sides	2-sided
lower limit	-10.59
upper limit	15.1
Notes [343] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	Emotional Impact on Parent Subscale score: DB Week 48
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	32
Analysis specification	Pre-specified
Analysis type	[344]
Method
Parameter type	Difference in LS Mean
Point estimate	-25.07
Confidence interval
level	95%
sides	2-sided
lower limit	-60.96
upper limit	10.82
Notes [344] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	Family Cohesion Subscale Score: DB Week 48
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	32
Analysis specification	Pre-specified
Analysis type	[345]
Method
Parameter type	Difference in LS Mean
Point estimate	-20.42
Confidence interval
level	95%
sides	2-sided
lower limit	-79.03
upper limit	38.18
Notes [345] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	Family Cohesion Subscale Score: DB Week 24
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	32
Analysis specification	Pre-specified
Analysis type	[346]
Method
Parameter type	Difference in LS Mean
Point estimate	-3.52
Confidence interval
level	95%
sides	2-sided
lower limit	-14.84
upper limit	7.81
Notes [346] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	Family Activities Subscale Score: DB Week 48
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	32
Analysis specification	Pre-specified
Analysis type	[347]
Method
Parameter type	Difference in LS Mean
Point estimate	-9.3
Confidence interval
level	95%
sides	2-sided
lower limit	-32.35
upper limit	13.75
Notes [347] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	Family Activities Subscale Score: DB Week 24
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	32
Analysis specification	Pre-specified
Analysis type	[348]
Method
Parameter type	Difference in LS Mean
Point estimate	-3.97
Confidence interval
level	95%
sides	2-sided
lower limit	-12.84
upper limit	4.9
Notes [348] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	Time Impact on Parent Subscale score: DB Week 48
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	32
Analysis specification	Pre-specified
Analysis type	[349]
Method
Parameter type	Difference in LS Mean
Point estimate	-9.19
Confidence interval
level	95%
sides	2-sided
lower limit	-48.91
upper limit	30.53
Notes [349] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	Time Impact on Parent Subscale score: DB Week 24
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	32
Analysis specification	Pre-specified
Analysis type	[350]
Method
Parameter type	Difference in LS Mean
Point estimate	1.87
Confidence interval
level	95%
sides	2-sided
lower limit	-13.55
upper limit	17.29
Notes [350] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.

Secondary: Change From Double-Blind Baseline in CHQ Responses at DB Weeks 24, 48: Double-Blind Phase Top of page

Secondary: Change From Open-Label Baseline in CHAQ-Discomfort Index at Part 1 Day 7, Weeks 2, 4, 8, 12, 16: Open-label Phase Part 1 Top of page
End point title	Change From Open-Label Baseline in CHAQ-Discomfort Index at Part 1 Day 7, Weeks 2, 4, 8, 12, 16: Open-label Phase Part 1 [351]
End point description	For the assessment of discomfort, the parent/legal guardian or adult caregiver who interacted daily with the participant were required to rate the overall pain the participant had due to illness by entering a number from 0 to 10 (in 0.5 increments), with ‘0’ as ‘No pain’ and ‘10’ as ‘Very severe pain’ on a 21-circle VAS. OLPT1 analysis set was used. All participants reported under ‘Number of Participants Analysed’ contributed data to the table; however, may not have evaluable data for every row. Here, “n” signifies number of participants evaluable for specified rows.
End point type	Secondary
End point timeframe	Baseline ((last value collected prior to Day 1 of tofacitinib administration in OL phase) Part 1 Day 7, Weeks 2, 4, 8, 12, 16
Notes [351] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint is specific to Open-Label period hence Open-Label arms have been reported.
End point values Tofacitinib 5mg BID Open_Label (OL) Part 1 Number of subjects analysed 100 Units: Units on a scale arithmetic mean (standard deviation)     Part 1 Day 7, n=99 -1.20 ( 1.77 )     Part 1 Week 2, n=98 -1.87 ( 2.07 )     Part 1 Week 4, n=97 -2.57 ( 2.14 )     Part 1 Week 8, n=82 -3.30 ( 2.45 )     Part 1 Week 12, n=44 -3.57 ( 2.50 )     Part 1 Week 16, n=24 -3.69 ( 2.28 )
No statistical analyses for this end point

Secondary: Change From Open-Label Baseline in CHAQ-Discomfort Index at Part 1 Day 7, Weeks 2, 4, 8, 12, 16: Open-label Phase Part 1 Top of page

Secondary: Change From Open-label Baseline in CHAQ-Discomfort Index at Part 2 Weeks 4, 8, 12, 16, 20, 24: Open-label Phase Part 2 Top of page
End point title	Change From Open-label Baseline in CHAQ-Discomfort Index at Part 2 Weeks 4, 8, 12, 16, 20, 24: Open-label Phase Part 2 [352]
End point description	For the assessment of discomfort, the parent/legal guardian or adult caregiver who interacted daily with the participant were required to rate the overall pain the participant had due to illness by entering a number from 0 to 10 (in 0.5 increments), with ‘0’ as ‘No pain’ and ‘10’ as ‘very severe pain’ on a 21-circle VAS. OLPT2 analysis set was used. All participants reported under ‘Number of Participants Analysed’ contributed data to the table; however, may not have evaluable data for every row. Here “Number Analysed” signifies number of participants evaluable for specified rows.
End point type	Secondary
End point timeframe	Baseline (last value collected prior to Day 1 of tofacitinib administration in OL phase) Part 2 Weeks 4, 8, 12, 16, 20, 24
Notes [352] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint is specific to Open-Label period hence Open-Label arms have been reported.
End point values Tofacitinib 5mg BID OL Part 2 Number of subjects analysed 54 Units: Units on a scale arithmetic mean (standard deviation)     Part 2 Week 4,n=50 -4.23 ( 3.14 )     Part 2 Week 8,n=40 -4.38 ( 2.95 )     Part 2 Week 12,n=31 -4.42 ( 3.26 )     Part 2 Week 16,n=23 -4.48 ( 2.88 )     Part 2 Week 20,n=13 -5.15 ( 3.52 )     Part 2 Week 24,n=3 -6.00 ( 1.73 )
No statistical analyses for this end point

Secondary: Change From Open-label Baseline in CHAQ-Discomfort Index at Part 2 Weeks 4, 8, 12, 16, 20, 24: Open-label Phase Part 2 Top of page

Secondary: Change From Double-Blind Baseline in CHAQ-Discomfort Index at DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52: Double-blind Phase Top of page
End point title	Change From Double-Blind Baseline in CHAQ-Discomfort Index at DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52: Double-blind Phase [353]
End point description	For the assessment of discomfort, the parent/legal guardian or adult caregiver who interacted daily with the participant were required to rate the overall pain the participant had due to illness by entering a number from 0 to 10 (in 0.5 increments), with ‘0’ as ‘No pain’ and ‘10’ as ‘very severe pain’ on a 21-circle VAS. DBFAS consisted of all randomised participants who received at least one dose of investigational product in the double-blind phase. Missing response was imputed as non-response.
End point type	Secondary
End point timeframe	DB Baseline (value at randomization), DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Notes [353] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint is specific to Double-Blind period hence Double-Blind arms have been reported.
End point values Tofacitinib 5mg BID Double-Blind (DB) Placebo DB Number of subjects analysed 28 31 Units: Units on a scale least squares mean (standard error)     DB Week 4(n=27,30) 0.13 ( 0.28 ) 0.37 ( 0.26 )     DB Week 8 (n=25,25) 0.56 ( 0.36 ) 0.02 ( 0.35 )     DB Week 12(n=21,23) 0.04 ( 0.34 ) 0.09 ( 0.32 )     DB Week 16 (n=21,20) 0.44 ( 0.36 ) -0.11 ( 0.35 )     DB Week 20 (n=19,15) 0.09 ( 0.40 ) -0.14 ( 0.42 )     DB Week 24 (n=18,15) 0.07 ( 0.27 ) -0.25 ( 0.28 )     DB Week 28 (n=17,12) -0.03 ( 0.47 ) 0.39 ( 0.51 )     DB Week 32(n=13,10) -0.31 ( 0.39 ) 0.01 ( 0.42 )     DB Week 36(n=13,10) -0.55 ( 0.34 ) -0.24 ( 0.37 )     DB Week 40(n=11,9) -0.76 ( 0.20 ) -0.83 ( 0.21 )     DB Week 44 (n=10, 9) -1.09 ( 0.23 ) -0.79 ( 0.24 )     DB Week 48 (n=8, 5) -0.19 ( 0.49 ) -0.43 ( 0.79 )     DB Week 52 (n=6, 5) -0.85 ( 0.21 ) -0.76 ( 0.34 )
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 4
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[354]
Method
Parameter type	Difference in LS Mean
Point estimate	-0.24
Confidence interval
level	95%
sides	2-sided
lower limit	-1.02
upper limit	0.54
Notes [354] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 12
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[355]
Method
Parameter type	Difference in LS Mean
Point estimate	0.47
Confidence interval
level	95%
sides	2-sided
lower limit	-1.01
upper limit	0.9
Notes [355] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 16
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[356]
Method
Parameter type	Difference in LS Mean
Point estimate	0.55
Confidence interval
level	95%
sides	2-sided
lower limit	-0.49
upper limit	1.58
Notes [356] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 20
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[357]
Method
Parameter type	Difference in LS Mean
Point estimate	0.23
Confidence interval
level	95%
sides	2-sided
lower limit	-0.98
upper limit	1.45
Notes [357] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 24
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[358]
Method
Parameter type	Difference in LS Mean
Point estimate	0.32
Confidence interval
level	95%
sides	2-sided
lower limit	-0.51
upper limit	1.14
Notes [358] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 52
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[359]
Method
Parameter type	Difference in LS Mean
Point estimate	-0.09
Confidence interval
level	95%
sides	2-sided
lower limit	-0.87
upper limit	0.69
Notes [359] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 32
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[360]
Method
Parameter type	Difference in LS Mean
Point estimate	-0.33
Confidence interval
level	95%
sides	2-sided
lower limit	-1.53
upper limit	0.88
Notes [360] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 36
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[361]
Method
Parameter type	Difference in LS Mean
Point estimate	-0.31
Confidence interval
level	95%
sides	2-sided
lower limit	-1.36
upper limit	0.74
Notes [361] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 40
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[362]
Method
Parameter type	Difference in LS Mean
Point estimate	0.07
Confidence interval
level	95%
sides	2-sided
lower limit	-0.55
upper limit	0.69
Notes [362] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 44
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[363]
Method
Parameter type	Difference in LS Mean
Point estimate	-0.31
Confidence interval
level	95%
sides	2-sided
lower limit	-1.01
upper limit	0.39
Notes [363] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 48
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[364]
Method
Parameter type	Difference in LS Mean
Point estimate	0.23
Confidence interval
level	95%
sides	2-sided
lower limit	-1.45
upper limit	1.92
Notes [364] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 8
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[365]
Method
Parameter type	Difference in LS Mean
Point estimate	0.54
Confidence interval
level	95%
sides	2-sided
lower limit	-0.49
upper limit	1.57
Notes [365] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 28
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[366]
Method
Parameter type	Difference in LS Mean
Point estimate	-0.42
Confidence interval
level	95%
sides	2-sided
lower limit	-1.87
upper limit	1.03
Notes [366] - Analysis performed using MMRM which included the fixed effect of treatment, visit, treatment by visit interaction, Double-Blind baseline value, and Double-Blind baseline value by visit interaction.

Secondary: Change From Double-Blind Baseline in CHAQ-Discomfort Index at DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52: Double-blind Phase Top of page

Secondary: Percentage of Participants With Minimum Disease Activity Calculated From JADAS-27 CRP Score at Part 1 Day 7, Weeks 2, 4, 8, 12 and 16: Open-label Phase Part 1 Top of page
End point title	Percentage of Participants With Minimum Disease Activity Calculated From JADAS-27 CRP Score at Part 1 Day 7, Weeks 2, 4, 8, 12 and 16: Open-label Phase Part 1 [367]
End point description	Minimal disease activity is defined as follows: Polyarthritis (>4 active joints): Minimal Disease Activity: less than equal (<=) 3.8. Oligoarthritis (<= 4 active joints): Minimal Disease Activity: <=2. OLPT1 analysis set was used. All participants reported under ‘Number of Participants Analysed’ contributed data to the table; however, may not have evaluable data for every row. Here, n=number of participants evaluable for the specified time points and used for calculating percentages.
End point type	Secondary
End point timeframe	Part 1 Day 7, Part 1 Weeks 2, 4, 8, 12 and 16
Notes [367] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint is specific to Open-Label period hence Open-Label arms have been reported.
End point values Tofacitinib 5mg BID Open_Label (OL) Part 1 Number of subjects analysed 100 Units: Percentage of participants number (confidence interval 95%)     Part 1 Day 7; n=97 3.09 (0 to 6.54)     Part 1 Week 2; n=96 5.21 (0.76 to 9.65)     Part 1 Week 4; n=97 6.19 (1.39 to 10.98)     Part 1 Week 8; n=80 13.75 (6.20 to 21.30)     Part 1 Week 12; n=44 13.64 (3.50 to 23.78)     Part 1 Week 16; n=24 25.00 (7.68 to 42.32)
No statistical analyses for this end point

Secondary: Percentage of Participants With Minimum Disease Activity Calculated From JADAS-27 CRP Score at Part 1 Day 7, Weeks 2, 4, 8, 12 and 16: Open-label Phase Part 1 Top of page

Secondary: Percentage of Participants With Minimum Disease Activity Calculated From JADAS-27 ESR Score at Part 1 Day 7, Weeks 2, 4, 8, 12 and 16: Open-label Phase Part 1 Top of page
End point title	Percentage of Participants With Minimum Disease Activity Calculated From JADAS-27 ESR Score at Part 1 Day 7, Weeks 2, 4, 8, 12 and 16: Open-label Phase Part 1 [368]
End point description	Minimal disease activity is defined as follows: Polyarthritis (>4 active joints): Minimal Disease Activity: less than equal (<=) 3.8. Oligoarthritis (<= 4 active joints): Minimal Disease Activity: <=2. OLPT1 analysis set was used. All participants reported under ‘Number of Participants Analysed’ contributed data to the table; however, may not have evaluable data for every row. Here, n=number of participants evaluable for the specified time points and used for calculating percentages.
End point type	Secondary
End point timeframe	Part 1 Day 7, Weeks 2, 4, 8, 12 and 16
Notes [368] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint is specific to Open-Label period hence Open-Label arms have been reported.
End point values Tofacitinib 5mg BID Open_Label (OL) Part 1 Number of subjects analysed 100 Units: Percentage of participants number (confidence interval 95%)     Part 1 Day 7: n=98 1.02 (0 to 3.01)     Part 1 Week 2: n=98 4.08 (0.16 to 8.00)     Part 1 Week 4: n=97 7.22 (2.07 to 12.37)     Part 1 Week 8: n=81 14.81 (7.08 to 22.55)     Part 1 Week 12: n=44 15.91 (5.10 to 26.72)     Part 1 Week 16: n=24 20.83 (4.59 to 37.08)
No statistical analyses for this end point

Secondary: Percentage of Participants With Minimum Disease Activity Calculated From JADAS-27 ESR Score at Part 1 Day 7, Weeks 2, 4, 8, 12 and 16: Open-label Phase Part 1 Top of page

Secondary: Percentage of Participants With Minimum Disease Activity Calculated From JADAS-27 CRP Score at Part 2 Weeks 4, 8, 12, 16, 20, 24: Open-label Phase Part 2 Top of page
End point title	Percentage of Participants With Minimum Disease Activity Calculated From JADAS-27 CRP Score at Part 2 Weeks 4, 8, 12, 16, 20, 24: Open-label Phase Part 2 [369]
End point description	Minimal disease activity is defined as follows: Polyarthritis (>4 active joints): Minimal Disease Activity: less than equal (<=) 3.8. Oligoarthritis (<= 4 active joints): Minimal Disease Activity: <=2. OLPT2 analysis set was used. All participants reported under ‘Number of Participants Analysed’ contributed data to the table; however, may not have evaluable data for every row. Here, n=number of participants evaluable for the specified time points and used for calculating percentages.
End point type	Secondary
End point timeframe	Part 2 Weeks 4, 8, 12, 16, 20, 24
Notes [369] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint is specific to Open-Label period hence Open-Label arms have been reported.
End point values Tofacitinib 5mg BID OL Part 2 Number of subjects analysed 54 Units: Percentage of participants number (confidence interval 95%)     Part 2 Week 4; n=50 36.00 (22.70 to 49.30)     Part 2 Week 8; n=40 30.00 (15.80 to 44.20)     Part 2 Week 12; n=31 32.26 (15.80 to 48.71)     Part 2 Week 16; n=22 36.36 (16.26 to 56.47)     Part 2 Week 20; n=13 53.85 (26.75 to 80.95)     Part 2 Week 24; n=3 33.33 (0 to 86.68)
No statistical analyses for this end point

Secondary: Percentage of Participants With Minimum Disease Activity Calculated From JADAS-27 CRP Score at Part 2 Weeks 4, 8, 12, 16, 20, 24: Open-label Phase Part 2 Top of page

Secondary: Percentage of Participants With Inactive Disease Status Calculated From JADAS-27 CRP Score at Part 1 Day 7, Weeks 2, 4, 8, 12 and 16: Open-label Phase Part 1 Top of page
End point title	Percentage of Participants With Inactive Disease Status Calculated From JADAS-27 CRP Score at Part 1 Day 7, Weeks 2, 4, 8, 12 and 16: Open-label Phase Part 1 [370]
End point description	Inactive Disease activity is defined as based on JADAS 27 score follows: Polyarthritis (>4 active joints): Inactive Disease: (<=1; Oligoarthritis (<= 4 active joints): Inactive Disease: (<=1. OLPT1 set was used. All participants reported under ‘Number of Participants Analysed’ contributed data to the table; however, may not have evaluable data for every row. Here, n=number of participants evaluable for the specified time points and used for calculating percentages.
End point type	Secondary
End point timeframe	Part 1 Day 7, Weeks 2, 4, 8, 12 and 16
Notes [370] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint is specific to Open-Label period hence Open-Label arms have been reported.
End point values Tofacitinib 5mg BID Open_Label (OL) Part 1 Number of subjects analysed 100 Units: Percentage of Participants number (confidence interval 95%)     Part 1 Day 7; n=97 0 (0 to 0)     Part 1 Week 2; n=96 3.13 (0 to 6.61)     Part 1 Week 4; n=97 3.09 (0 to 6.54)     Part 1 Week 8; n=80 5.00 (0.22 to 9.78)     Part 1 Week 12; n=44 4.55 (0 to 10.70)     Part 1 Week 16; n=24 4.17 (0 to 12.16)
No statistical analyses for this end point

Secondary: Percentage of Participants With Inactive Disease Status Calculated From JADAS-27 CRP Score at Part 1 Day 7, Weeks 2, 4, 8, 12 and 16: Open-label Phase Part 1 Top of page

Secondary: Percentage of Participants With Minimum Disease Activity Calculated From JADAS-27 ESR Score at Part 2 Weeks 4, 8, 12, 16, 20, 24: Open-label Phase Part 2 Top of page
End point title	Percentage of Participants With Minimum Disease Activity Calculated From JADAS-27 ESR Score at Part 2 Weeks 4, 8, 12, 16, 20, 24: Open-label Phase Part 2 [371]
End point description	Minimal disease activity is defined as follows: Polyarthritis (>4 active joints): Minimal Disease Activity: less than equal (<=) 3.8. Oligoarthritis (<= 4 active joints): Minimal Disease Activity: <=2. OLPT2 analysis set was used. All participants reported under ‘Number of Participants Analysed’ contributed data to the table; however, may not have evaluable data for every row. Here, n=number of participants evaluable for the specified time points and used for calculating percentages.
End point type	Secondary
End point timeframe	Part 2 Weeks 4, 8, 12, 16, 20, 24
Notes [371] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint is specific to Open-Label period hence Open-Label arms have been reported.
End point values Tofacitinib 5mg BID OL Part 2 Number of subjects analysed 54 Units: Percentage of participants number (confidence interval 95%)     Part 2 Week 4; n=50 32.00 (19.07 to 44.93)     Part 2 Week 8; n=40 27.50 (13.66 to 41.34)     Part 2 Week 12; n=31 29.03 (13.05 to 45.01)     Part 2 Week 16; n=23 34.78 (15.32 to 54.25)     Part 2 Week 20; n=13 53.85 (26.75 to 80.95)     Part 2 Week 24; n=3 33.33 (0 to 86.68)
No statistical analyses for this end point

Secondary: Percentage of Participants With Minimum Disease Activity Calculated From JADAS-27 ESR Score at Part 2 Weeks 4, 8, 12, 16, 20, 24: Open-label Phase Part 2 Top of page

Secondary: Percentage of Participants With Inactive Disease Status Calculated From JADAS-27 ESR Score at Part 1 Day 7, Weeks 2, 4, 8, 12 and 16: Open-label Phase Part 1 Top of page
End point title	Percentage of Participants With Inactive Disease Status Calculated From JADAS-27 ESR Score at Part 1 Day 7, Weeks 2, 4, 8, 12 and 16: Open-label Phase Part 1 [372]
End point description	Inactive disease activity is defined as based on JADAS 27 score follows: Polyarthritis (>4 active joints): Inactive Disease: (<=1; Oligoarthritis (<= 4 active joints): Inactive Disease: (<=1. OLPT1 set was used. All participants reported under ‘Number of Participants Analysed’ contributed data to the table; however, may not have evaluable data for every row. Here, n=number of participants evaluable for the specified time points and used for calculating percentages.
End point type	Secondary
End point timeframe	Part 1 Day 7, Weeks 2, 4, 8, 12 and 16
Notes [372] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint is specific to Open-Label period hence Open-Label arms have been reported.
End point values Tofacitinib 5mg BID Open_Label (OL) Part 1 Number of subjects analysed 100 Units: Percentage of Participants number (confidence interval 95%)     Part 1 Day 7; n=98 0 (0 to 0)     Part 1 Week 2; n=98 2.04 (0 to 4.84)     Part 1 Week 4; n=97 1.03 (0 to 3.04)     Part 1 Week 8; n=81 3.70 (0 to 7.82)     Part 1 Week 12; n=44 6.82 (0 to 14.27)     Part 1 Week 16; n=24 4.17 (0 to 12.16)
No statistical analyses for this end point

Secondary: Percentage of Participants With Inactive Disease Status Calculated From JADAS-27 ESR Score at Part 1 Day 7, Weeks 2, 4, 8, 12 and 16: Open-label Phase Part 1 Top of page

Secondary: Percentage of Participants With Inactive Disease Status Calculated From JADAS-27 CRP Score at Part 2 Weeks 4, 8, 12, 16, 20, 24: Open-label Phase Part 2 Top of page
End point title	Percentage of Participants With Inactive Disease Status Calculated From JADAS-27 CRP Score at Part 2 Weeks 4, 8, 12, 16, 20, 24: Open-label Phase Part 2 [373]
End point description	Inactive disease activity is defined as based on JADAS 27 score follows: Polyarthritis (>4 active joints): Inactive Disease: (<=1; Oligoarthritis (<= 4 active joints): Inactive Disease: (<=1. OLPT2 set was used. All participants reported under ‘Number of Participants Analysed’ contributed data to the table; however, may not have evaluable data for every row. Here, n=number of participants evaluable for the specified time points and used for calculating percentages.
End point type	Secondary
End point timeframe	Part 2 Weeks 4, 8, 12, 16, 20, 24
Notes [373] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint is specific to Open-Label period hence Open-Label arms have been reported.
End point values Tofacitinib 5mg BID OL Part 2 Number of subjects analysed 54 Units: Percentage of Participants number (confidence interval 95%)     Part 2 Week 4; n=50 16.00 (5.84 to 26.16)     Part 2 Week 8; n=40 20.00 (7.60 to 32.40)     Part 2 Week 12; n=31 9.68 (0 to 20.09)     Part 2 Week 16; n=22 18.18 (2.06 to 34.30)     Part 2 Week 20; n=13 38.46 (12.01 to 64.91)     Part 2 Week 24; n=3 33.33 (0 to 86.68)
No statistical analyses for this end point

Secondary: Percentage of Participants With Inactive Disease Status Calculated From JADAS-27 CRP Score at Part 2 Weeks 4, 8, 12, 16, 20, 24: Open-label Phase Part 2 Top of page

Secondary: Percentage of Participants With Inactive Disease Status Calculated From JADAS-27 ESR Score at Part 2 Weeks 4, 8, 12, 16, 20, 24: Open-label Phase Part 2 Top of page
End point title	Percentage of Participants With Inactive Disease Status Calculated From JADAS-27 ESR Score at Part 2 Weeks 4, 8, 12, 16, 20, 24: Open-label Phase Part 2 [374]
End point description	Inactive Disease activity is defined as based on JADAS 27 score follows: Polyarthritis (>4 active joints): Inactive Disease: (<=1; Oligoarthritis (<= 4 active joints): Inactive Disease: (<=1. OLPT2 set was used. All participants reported under ‘Number of Participants Analysed’ contributed data to the table; however, may not have evaluable data for every row. Here, n=number of participants evaluable for the specified time points and used for calculating percentages.
End point type	Secondary
End point timeframe	Part 2 Weeks 4, 8, 12, 16, 20, 24
Notes [374] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint is specific to Open-Label period hence Open-Label arms have been reported.
End point values Tofacitinib 5mg BID OL Part 2 Number of subjects analysed 54 Units: Percentage of Participants number (confidence interval 95%)     Part 2 Week 4; n=50 16.00 (5.84 to 26.16)     Part 2 Week 8; n=40 17.50 (5.72 to 29.28)     Part 2 Week 12; n=31 9.68 (0 to 20.09)     Part 2 Week 16; n=23 17.39 (1.90 to 32.88)     Part 2 Week 20; n=13 46.15 (19.05 to 73.25)     Part 2 Week 24; n=3 33.33 (0 to 86.68)
No statistical analyses for this end point

Secondary: Percentage of Participants With Inactive Disease Status Calculated From JADAS-27 ESR Score at Part 2 Weeks 4, 8, 12, 16, 20, 24: Open-label Phase Part 2 Top of page

Secondary: Percentage of Participants With Minimum Disease Activity Calculated From JADAS-27 CRP Score at DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52: Double-blind Phase Top of page
End point title	Percentage of Participants With Minimum Disease Activity Calculated From JADAS-27 CRP Score at DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52: Double-blind Phase [375]
End point description	Minimal disease activity is defined as follows: Polyarthritis (>4 active joints): Minimal Disease Activity: less than equal (<=) 3.8. Oligoarthritis (<= 4 active joints): Minimal Disease Activity: <=2. DBFAS analysis set was used. Missing response was imputed as non-response.
End point type	Secondary
End point timeframe	DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52
Notes [375] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint is specific to Double-Blind period hence Double-Blind arms have been reported.
End point values Tofacitinib 5mg BID Double-Blind (DB) Placebo DB Number of subjects analysed 28 31 Units: Percentage of Participants number (not applicable)     DB Week 4 21.43 51.61     DB Week 8 25.00 48.39     DB Week 12 32.14 32.26     DB Week 16 35.71 29.03     DB Week 20 35.71 22.58     DB Week 24 35.71 35.48     DB Week 28 35.71 32.26     DB Week 32 28.57 22.58     DB Week 36 39.29 35.48     DB Week 40 39.29 29.03     DB Week 44 46.43 25.81     DB Week 48 46.43 25.81     DB Week 52 46.43 29.03
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 12
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[376]
Method
Parameter type	Difference in percentage
Point estimate	-0.12
Confidence interval
level	95%
sides	2-sided
lower limit	-23.99
upper limit	23.76
Notes [376] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 8
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[377]
Method
Parameter type	Difference in percentage
Point estimate	-23.39
Confidence interval
level	95%
sides	2-sided
lower limit	-47.19
upper limit	0.42
Notes [377] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 4
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[378]
Method
Parameter type	Difference in percentage
Point estimate	-30.18
Confidence interval
level	95%
sides	2-sided
lower limit	-53.43
upper limit	-6.94
Notes [378] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 52
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[379]
Method
Parameter type	Difference in percentage
Point estimate	17.4
Confidence interval
level	95%
sides	2-sided
lower limit	-7.03
upper limit	41.82
Notes [379] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 32
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[380]
Method
Parameter type	Difference in percentage
Point estimate	5.99
Confidence interval
level	95%
sides	2-sided
lower limit	-16.29
upper limit	28.28
Notes [380] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 36
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[381]
Method
Parameter type	Difference in percentage
Point estimate	3.8
Confidence interval
level	95%
sides	2-sided
lower limit	-20.92
upper limit	28.52
Notes [381] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 40
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[382]
Method
Parameter type	Difference in percentage
Point estimate	10.25
Confidence interval
level	95%
sides	2-sided
lower limit	-13.88
upper limit	34.39
Notes [382] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 44
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[383]
Method
Parameter type	Difference in percentage
Point estimate	20.62
Confidence interval
level	95%
sides	2-sided
lower limit	-3.43
upper limit	44.67
Notes [383] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 48
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[384]
Method
Parameter type	Difference in percentage
Point estimate	20.62
Confidence interval
level	95%
sides	2-sided
lower limit	-3.43
upper limit	44.67
Notes [384] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 24
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[385]
Method
Parameter type	Difference in percentage
Point estimate	0.23
Confidence interval
level	95%
sides	2-sided
lower limit	-24.24
upper limit	24.7
Notes [385] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 20
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[386]
Method
Parameter type	Difference in percentage
Point estimate	13.13
Confidence interval
level	95%
sides	2-sided
lower limit	-9.92
upper limit	36.19
Notes [386] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 16
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[387]
Method
Parameter type	Difference in percentage
Point estimate	6.68
Confidence interval
level	95%
sides	2-sided
lower limit	-17.2
upper limit	30.56
Notes [387] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 28
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[388]
Method
Parameter type	Difference in percentage
Point estimate	3.46
Confidence interval
level	95%
sides	2-sided
lower limit	-20.75
upper limit	27.66
Notes [388] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.

Secondary: Percentage of Participants With Minimum Disease Activity Calculated From JADAS-27 CRP Score at DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52: Double-blind Phase Top of page

Secondary: Percentage of Participants With Minimum Disease Activity Calculated From JADAS-27 ESR Score at DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52: Double-blind Phase Top of page
End point title	Percentage of Participants With Minimum Disease Activity Calculated From JADAS-27 ESR Score at DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52: Double-blind Phase [389]
End point description	Minimal disease activity is defined as follows: Polyarthritis (>4 active joints): Minimal Disease Activity: less than equal (<=) 3.8. Oligoarthritis (<= 4 active joints): Minimal Disease Activity: <=2. DBFAS analysis set was used. Missing response was imputed as non-response.
End point type	Secondary
End point timeframe	DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52
Notes [389] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint is specific to Double-Blind period hence Double-Blind arms have been reported.
End point values Tofacitinib 5mg BID Double-Blind (DB) Placebo DB Number of subjects analysed 28 31 Units: Percentage of Participants number (not applicable)     DB Week 4 25.00 51.61     DB Week 8 25.00 45.16     DB Week 12 32.14 41.94     DB Week 16 35.71 35.48     DB Week 20 39.29 29.03     DB Week 24 35.71 38.71     DB Week 28 35.71 38.71     DB Week 32 28.57 35.48     DB Week 36 39.29 35.48     DB Week 40 39.29 32.26     DB Week 44 50.00 32.26     DB Week 48 50.00 35.48     DB Week 52 50.00 32.26
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 4
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[390]
Method
Parameter type	Difference in percentage
Point estimate	-26.61
Confidence interval
level	95%
sides	2-sided
lower limit	-50.42
upper limit	-2.81
Notes [390] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 8
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[391]
Method
Parameter type	Difference in percentage
Point estimate	-20.16
Confidence interval
level	95%
sides	2-sided
lower limit	-43.91
upper limit	3.59
Notes [391] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 12
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[392]
Method
Parameter type	Difference in percentage
Point estimate	-9.79
Confidence interval
level	95%
sides	2-sided
lower limit	-34.31
upper limit	14.72
Notes [392] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 16
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[393]
Method
Parameter type	Difference in percentage
Point estimate	0.23
Confidence interval
level	95%
sides	2-sided
lower limit	-24.24
upper limit	24.7
Notes [393] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 20
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[394]
Method
Parameter type	Difference in percentage
Point estimate	10.25
Confidence interval
level	95%
sides	2-sided
lower limit	-13.88
upper limit	34.39
Notes [394] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 24
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[395]
Method
Parameter type	Difference in percentage
Point estimate	-3
Confidence interval
level	95%
sides	2-sided
lower limit	-27.67
upper limit	21.68
Notes [395] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 28
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[396]
Method
Parameter type	Difference in percentage
Point estimate	-3
Confidence interval
level	95%
sides	2-sided
lower limit	-27.67
upper limit	21.68
Notes [396] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 32
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[397]
Method
Parameter type	Difference in percentage
Point estimate	-6.91
Confidence interval
level	95%
sides	2-sided
lower limit	-30.65
upper limit	16.83
Notes [397] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 36
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[398]
Method
Parameter type	Difference in percentage
Point estimate	3.8
Confidence interval
level	95%
sides	2-sided
lower limit	-20.92
upper limit	28.52
Notes [398] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 40
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[399]
Method
Parameter type	Difference in percentage
Point estimate	7.03
Confidence interval
level	95%
sides	2-sided
lower limit	-17.43
upper limit	31.48
Notes [399] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 44
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[400]
Method
Parameter type	Difference in percentage
Point estimate	17.74
Confidence interval
level	95%
sides	2-sided
lower limit	-7.03
upper limit	42.52
Notes [400] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 48
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[401]
Method
Parameter type	Difference in percentage
Point estimate	14.52
Confidence interval
level	95%
sides	2-sided
lower limit	-10.52
upper limit	39.55
Notes [401] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 52
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[402]
Method
Parameter type	Difference in percentage
Point estimate	17.74
Confidence interval
level	95%
sides	2-sided
lower limit	-7.03
upper limit	42.52
Notes [402] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.

Secondary: Percentage of Participants With Minimum Disease Activity Calculated From JADAS-27 ESR Score at DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52: Double-blind Phase Top of page

Secondary: Percentage of Participants With Inactive Disease Status Calculated From JADAS-27 CRP Score at DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52: Double-blind Phase Top of page
End point title	Percentage of Participants With Inactive Disease Status Calculated From JADAS-27 CRP Score at DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52: Double-blind Phase [403]
End point description	Inactive disease activity is defined as based on JADAS 27 score follows: Polyarthritis (>4 active joints): Inactive Disease: (<=1; Oligoarthritis (<= 4 active joints): Inactive Disease: (<=1. DBFAS set was used. Missing response was imputed as non-response.
End point type	Secondary
End point timeframe	DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52
Notes [403] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint is specific to Double-Blind period hence Double-Blind arms have been reported.
End point values Tofacitinib 5mg BID Double-Blind (DB) Placebo DB Number of subjects analysed 28 31 Units: Percentage of Participants number (not applicable)     DB Week 4 10.71 25.81     DB Week 8 7.14 19.35     DB Week 12 7.14 16.13     DB Week 16 14.29 9.68     DB Week 20 14.29 9.68     DB Week 24 7.14 16.13     DB Week 28 10.71 22.58     DB Week 32 14.29 19.35     DB Week 36 10.71 16.13     DB Week 40 14.29 25.81     DB Week 44 14.29 16.13     DB Week 48 10.71 19.35     DB Week 52 14.29 19.35
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 4
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[404]
Method
Parameter type	Difference in percentage
Point estimate	-15.09
Confidence interval
level	95%
sides	2-sided
lower limit	-34.29
upper limit	4.1
Notes [404] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 12
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[405]
Method
Parameter type	Difference in percentage
Point estimate	-8.99
Confidence interval
level	95%
sides	2-sided
lower limit	-25.07
upper limit	7.1
Notes [405] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 16
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[406]
Method
Parameter type	Difference in percentage
Point estimate	4.61
Confidence interval
level	95%
sides	2-sided
lower limit	-12.01
upper limit	21.23
Notes [406] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 20
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[407]
Method
Parameter type	Difference in percentage
Point estimate	4.61
Confidence interval
level	95%
sides	2-sided
lower limit	-12.01
upper limit	21.23
Notes [407] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 24
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[408]
Method
Parameter type	Difference in percentage
Point estimate	-8.99
Confidence interval
level	95%
sides	2-sided
lower limit	-25.07
upper limit	7.1
Notes [408] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 8
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[409]
Method
Parameter type	Difference in percentage
Point estimate	-12.21
Confidence interval
level	95%
sides	2-sided
lower limit	-29.08
upper limit	4.65
Notes [409] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 28
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[410]
Method
Parameter type	Difference in percentage
Point estimate	-11.87
Confidence interval
level	95%
sides	2-sided
lower limit	-30.52
upper limit	6.79
Notes [410] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 32
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[411]
Method
Parameter type	Difference in percentage
Point estimate	-5.07
Confidence interval
level	95%
sides	2-sided
lower limit	-24.08
upper limit	13.94
Notes [411] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 36
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[412]
Method
Parameter type	Difference in percentage
Point estimate	-5.41
Confidence interval
level	95%
sides	2-sided
lower limit	-22.7
upper limit	11.87
Notes [412] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 40
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[413]
Method
Parameter type	Difference in percentage
Point estimate	-11.52
Confidence interval
level	95%
sides	2-sided
lower limit	-31.65
upper limit	8.61
Notes [413] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 44
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[414]
Method
Parameter type	Difference in percentage
Point estimate	-1.84
Confidence interval
level	95%
sides	2-sided
lower limit	-20.16
upper limit	16.48
Notes [414] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 48
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[415]
Method
Parameter type	Difference in percentage
Point estimate	-8.64
Confidence interval
level	95%
sides	2-sided
lower limit	-26.66
upper limit	9.38
Notes [415] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 52
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[416]
Method
Parameter type	Difference in percentage
Point estimate	-5.07
Confidence interval
level	95%
sides	2-sided
lower limit	-24.08
upper limit	13.94
Notes [416] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.

Secondary: Percentage of Participants With Inactive Disease Status Calculated From JADAS-27 CRP Score at DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52: Double-blind Phase Top of page

Secondary: Percentage of Participants With Inactive Disease Status Calculated From JADAS-27 ESR Score at DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52: Double-blind Phase Top of page
End point title	Percentage of Participants With Inactive Disease Status Calculated From JADAS-27 ESR Score at DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52: Double-blind Phase [417]
End point description	Inactive disease activity is defined as based on JADAS 27 score follows: Polyarthritis (>4 active joints): Inactive Disease: (<=1; Oligoarthritis (<= 4 active joints): Inactive Disease: (<=1. DBFAS set was used. Missing response was imputed as non-response.
End point type	Secondary
End point timeframe	DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52
Notes [417] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint is specific to Double-Blind period hence Double-Blind arms have been reported.
End point values Tofacitinib 5mg BID Double-Blind (DB) Placebo DB Number of subjects analysed 28 31 Units: Percentage of Participants number (not applicable)     DB Week 4 7.14 19.35     DB Week 8 14.29 29.03     DB Week 12 14.29 22.58     DB Week 16 17.86 16.13     DB Week 20 14.29 12.90     DB Week 24 10.71 16.13     DB Week 28 10.71 22.58     DB Week 32 14.29 19.35     DB Week 36 10.71 19.35     DB Week 40 14.29 25.81     DB Week 44 14.29 22.58     DB Week 48 14.29 22.58     DB Week 52 14.29 19.35
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 8
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[418]
Method
Parameter type	Difference in percentage
Point estimate	-14.75
Confidence interval
level	95%
sides	2-sided
lower limit	-35.32
upper limit	5.83
Notes [418] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 4
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[419]
Method
Parameter type	Difference in percentage
Point estimate	-12.21
Confidence interval
level	95%
sides	2-sided
lower limit	-29.08
upper limit	4.65
Notes [419] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 12
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[420]
Method
Parameter type	Difference in percentage
Point estimate	-8.29
Confidence interval
level	95%
sides	2-sided
lower limit	-27.91
upper limit	11.32
Notes [420] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 28
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[421]
Method
Parameter type	Difference in percentage
Point estimate	-11.87
Confidence interval
level	95%
sides	2-sided
lower limit	-30.52
upper limit	6.79
Notes [421] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 32
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[422]
Method
Parameter type	Difference in percentage
Point estimate	-5.07
Confidence interval
level	95%
sides	2-sided
lower limit	-24.08
upper limit	13.94
Notes [422] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 36
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[423]
Method
Parameter type	Difference in percentage
Point estimate	-8.64
Confidence interval
level	95%
sides	2-sided
lower limit	-26.66
upper limit	9.38
Notes [423] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 44
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[424]
Method
Parameter type	Difference in percentage
Point estimate	-8.29
Confidence interval
level	95%
sides	2-sided
lower limit	-27.91
upper limit	11.32
Notes [424] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 48
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[425]
Method
Parameter type	Difference in percentage
Point estimate	-8.29
Confidence interval
level	95%
sides	2-sided
lower limit	-27.91
upper limit	11.32
Notes [425] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 52
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[426]
Method
Parameter type	Difference in percentage
Point estimate	-5.07
Confidence interval
level	95%
sides	2-sided
lower limit	-24.08
upper limit	13.94
Notes [426] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 24
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[427]
Method
Parameter type	Difference in percentage
Point estimate	-5.41
Confidence interval
level	95%
sides	2-sided
lower limit	-22.7
upper limit	11.87
Notes [427] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 20
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[428]
Method
Parameter type	Difference in percentage
Point estimate	1.38
Confidence interval
level	95%
sides	2-sided
lower limit	-16.15
upper limit	18.91
Notes [428] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 16
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[429]
Method
Parameter type	Difference in percentage
Point estimate	1.73
Confidence interval
level	95%
sides	2-sided
lower limit	-17.48
upper limit	20.93
Notes [429] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 40
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[430]
Method
Parameter type	Difference in percentage
Point estimate	-11.52
Confidence interval
level	95%
sides	2-sided
lower limit	-31.65
upper limit	8.61
Notes [430] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.

Secondary: Percentage of Participants With Inactive Disease Status Calculated From JADAS-27 ESR Score at DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52: Double-blind Phase Top of page

Secondary: Percentage of Participants with JIA ACR Inactive Disease Status at Part 1 Days 3, 7, Weeks 2, 4, 8, 12, 16: Open-label Phase Part 1 Top of page
End point title	Percentage of Participants with JIA ACR Inactive Disease Status at Part 1 Days 3, 7, Weeks 2, 4, 8, 12, 16: Open-label Phase Part 1 [431]
End point description	The ACR clinical inactive disease was defined as follows: no joints with active arthritis; no fever, rash, serositis, splenomegaly, hepatomegaly, or generalized lymphadenopathy attributable to sJIA; no active uveitis; normal ESR (within normal limits of the method used where tested) or, if elevated, not attributable to JIA; physician global assessment of disease activity score of ‘best possible’ on the scale used; duration of morning stiffness of <=15 minutes. 95% CI was based on normal approximation. OLPT1 set was used. n=number of participants evaluable for the specified time points and used for calculating percentages.
End point type	Secondary
End point timeframe	Baseline ((last value collected prior to Day 1 of tofacitinib administration in OL phase) Part 1 Days 3, 7, Weeks 2, 4, 8, 12, 16
Notes [431] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint is specific to Open-Label period hence Open-Label arms have been reported.
End point values Tofacitinib 5mg BID Open_Label (OL) Part 1 Number of subjects analysed 100 Units: Percentage of Participants number (confidence interval 95%)     Baseline; n=100 0 (0 to 0)     Part 1 Day 3; n=96 0 (0 to 0)     Part 1 Day 7; n=99 0 (0 to 0)     Part 1 Week 2; n=99 2.02 (0 to 4.79)     Part 1 Week 4; n=97 3.09 (0 to 6.54)     Part 1 Week 8; n=83 4.82 (0.21 to 9.43)     Part 1 Week 12; n=44 4.55 (0 to 10.70)     Part 1 Week 16; n=24 4.17 (0 to 12.16)
No statistical analyses for this end point

Secondary: Percentage of Participants with JIA ACR Inactive Disease Status at Part 1 Days 3, 7, Weeks 2, 4, 8, 12, 16: Open-label Phase Part 1 Top of page

Secondary: Percentage of Participants with JIA ACR Inactive Disease Status at Part 2 Weeks 4, 8, 12, 16, 20, 24: Open-label Phase Part 2 Top of page
End point title	Percentage of Participants with JIA ACR Inactive Disease Status at Part 2 Weeks 4, 8, 12, 16, 20, 24: Open-label Phase Part 2 [432]
End point description	The ACR clinical inactive disease was defined as follows: no joints with active arthritis; no fever, rash, serositis, splenomegaly, hepatomegaly, or generalized lymphadenopathy attributable to sJIA; no active uveitis; normal ESR (within normal limits of the method used where tested) or, if elevated, not attributable to JIA; physician global assessment of disease activity score of ‘best possible’ on the scale used; duration of morning stiffness of <=15 minutes. 95% CI was based on normal approximation. OLPT2 was used. All participants reported under ‘Number of Participants Analysed’ contributed data to the table; however, may not have evaluable data for every row. n=number of participants evaluable for the specified time points and used for calculating percentages.
End point type	Secondary
End point timeframe	Part 2 Weeks 4, 8, 12, 16, 20, 24
Notes [432] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint is specific to Open-Label period hence Open-Label arms have been reported.
End point values Tofacitinib 5mg BID OL Part 2 Number of subjects analysed 54 Units: Percentage of participants number (confidence interval 95%)     Part 2 Week 4;n=50 14.00 (4.38 to 23.62)     Part 2 Week 8;n=39 10.26 (0.73 to 19.78)     Part 2 Week 12;n=31 6.45 (0 to 15.10)     Part 2 Week 16;n=23 13.04 (0 to 26.81)     Part 2 Week 20;n=13 15.38 (0 to 35.00)     Part 2 Week 24;n=3 33.33 (0 to 86.68)
No statistical analyses for this end point

Secondary: Percentage of Participants with JIA ACR Inactive Disease Status at Part 2 Weeks 4, 8, 12, 16, 20, 24: Open-label Phase Part 2 Top of page

Secondary: Percentage of Participants with JIA ACR Inactive Disease Status at DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52: Double-blind Phase Top of page
End point title	Percentage of Participants with JIA ACR Inactive Disease Status at DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52: Double-blind Phase [433]
End point description	The ACR clinical inactive disease was defined as follows: no joints with active arthritis; no fever, rash, serositis, splenomegaly, hepatomegaly, or generalized lymphadenopathy attributable to sJIA; no active uveitis; normal ESR (within normal limits of the method used where tested) or, if elevated, not attributable to JIA; physician global assessment of disease activity score of ‘best possible’ on the scale used; duration of morning stiffness of <=15 minutes. 95% CI was based on normal approximation. DBFAS was used. Missing response was imputed as non-response.
End point type	Secondary
End point timeframe	DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Notes [433] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint is specific to Double-Blind period hence Double-Blind arms have been reported.
End point values Tofacitinib 5mg BID Double-Blind (DB) Placebo DB Number of subjects analysed 28 31 Units: Percentage of Participants number (not applicable)     DB Week 4 7.14 16.13     DB Week 8 3.57 22.58     DB Week 12 7.14 22.58     DB Week 16 3.57 16.13     DB Week 20 7.14 16.13     DB Week 24 7.14 19.35     DB Week 28 10.71 19.35     DB Week 32 10.71 19.35     DB Week 36 14.29 16.13     DB Week 40 17.86 22.58     DB Week 44 14.29 22.58     DB Week 48 17.86 22.58     DB Week 52 21.43 19.35
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	other [434]
Method
Parameter type	Difference in percentage
Point estimate	-15.44
Confidence interval
level	95%
sides	2-sided
lower limit	-32.98
upper limit	2.1
Notes [434] - DB Week 12
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 8
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	other [435]
Method
Parameter type	Difference in percentage
Point estimate	-19.01
Confidence interval
level	95%
sides	2-sided
lower limit	-35.25
upper limit	-2.76
Notes [435] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	other [436]
Method
Parameter type	Difference in percentage
Point estimate	-8.99
Confidence interval
level	95%
sides	2-sided
lower limit	-25.07
upper limit	7.1
Notes [436] - DB Week 4
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	other [437]
Method
Parameter type	Difference in percentage
Point estimate	2.07
Confidence interval
level	95%
sides	2-sided
lower limit	-18.53
upper limit	22.68
Notes [437] - DB Week 52
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	other [438]
Method
Parameter type	Difference in percentage
Point estimate	-8.64
Confidence interval
level	95%
sides	2-sided
lower limit	-26.66
upper limit	9.38
Notes [438] - DB Week 32
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	other [439]
Method
Parameter type	Difference in percentage
Point estimate	-1.84
Confidence interval
level	95%
sides	2-sided
lower limit	-20.16
upper limit	16.48
Notes [439] - DB Week 36
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	other [440]
Method
Parameter type	Difference in percentage
Point estimate	-4.72
Confidence interval
level	95%
sides	2-sided
lower limit	-25.17
upper limit	15.72
Notes [440] - DB Week 40
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	other [441]
Method
Parameter type	Difference in percentage
Point estimate	-8.29
Confidence interval
level	95%
sides	2-sided
lower limit	-27.91
upper limit	11.32
Notes [441] - DB Week 44
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	other [442]
Method
Parameter type	Difference in percentage
Point estimate	-4.72
Confidence interval
level	95%
sides	2-sided
lower limit	-25.17
upper limit	15.72
Notes [442] - DB Week 48
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	other [443]
Method
Parameter type	Difference in percentage
Point estimate	-12.21
Confidence interval
level	95%
sides	2-sided
lower limit	-29.08
upper limit	4.65
Notes [443] - DB Week 24
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	other [444]
Method
Parameter type	Difference in percentage
Point estimate	-8.99
Confidence interval
level	95%
sides	2-sided
lower limit	-25.07
upper limit	7.1
Notes [444] - DB Week 20
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	other [445]
Method
Parameter type	Difference in percentage
Point estimate	-12.56
Confidence interval
level	95%
sides	2-sided
lower limit	-27.22
upper limit	2.1
Notes [445] - DB Week 16
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	other [446]
Method
Parameter type	Difference in percentage
Point estimate	-8.64
Confidence interval
level	95%
sides	2-sided
lower limit	-26.66
upper limit	9.38
Notes [446] - DB Week 28

Secondary: Percentage of Participants with JIA ACR Inactive Disease Status at DB Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52: Double-blind Phase Top of page

Secondary: Percentage of Participants with JIA ACR Clinical Remission at DB Weeks 24, 28, 32, 36, 40, 44, 48, 52: Double-blind Phase Top of page
End point title	Percentage of Participants with JIA ACR Clinical Remission at DB Weeks 24, 28, 32, 36, 40, 44, 48, 52: Double-blind Phase [447]
End point description	According to ACR, clinical remission was defined as clinical inactive disease for 24 weeks continuously while on medications. DBFAS was used. Missing response was imputed as non-response.
End point type	Secondary
End point timeframe	DB Weeks 24, 28, 32, 36, 40, 44, 48, 52
Notes [447] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint is specific to Double-Blind period hence Double-Blind arms have been reported.
End point values Tofacitinib 5mg BID Double-Blind (DB) Placebo DB Number of subjects analysed 28 31 Units: Percentage of participants number (not applicable)     DB Week 24 0 3.23     DB Week 28 0 3.23     DB Week 32 0 3.23     DB Week 36 3.57 3.23     DB Week 40 3.57 3.23     DB Week 44 3.57 6.45     DB Week 48 3.57 9.68     DB Week 52 3.57 9.68
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 24
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[448]
Method
Parameter type	Difference in percentage
Point estimate	-2.96
Confidence interval
level	95%
sides	2-sided
lower limit	-11.69
upper limit	5.76
Notes [448] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 32
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[449]
Method
Parameter type	Difference in percentage
Point estimate	-2.96
Confidence interval
level	95%
sides	2-sided
lower limit	-11.69
upper limit	5.76
Notes [449] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 28
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[450]
Method
Parameter type	Difference in percentage
Point estimate	-2.96
Confidence interval
level	95%
sides	2-sided
lower limit	-11.69
upper limit	5.76
Notes [450] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 48
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[451]
Method
Parameter type	Difference in percentage
Point estimate	-6.11
Confidence interval
level	95%
sides	2-sided
lower limit	-18.58
upper limit	6.37
Notes [451] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 44
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[452]
Method
Parameter type	Difference in percentage
Point estimate	-2.88
Confidence interval
level	95%
sides	2-sided
lower limit	-13.93
upper limit	8.17
Notes [452] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 40
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[453]
Method
Parameter type	Difference in percentage
Point estimate	0.35
Confidence interval
level	95%
sides	2-sided
lower limit	-8.92
upper limit	9.62
Notes [453] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 52
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[454]
Method	Mixed Model for Repeated Measures
Parameter type	Difference in percentage
Point estimate	-6.11
Confidence interval
level	95%
sides	2-sided
lower limit	-18.58
upper limit	6.37
Notes [454] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.
Statistical analysis title	Tofacitinib 5mg BID DB and Placebo DB
Statistical analysis description	DB Week 36
Comparison groups	Tofacitinib 5mg BID Double-Blind (DB) v Placebo DB
Number of subjects included in analysis	59
Analysis specification	Pre-specified
Analysis type	[455]
Method
Parameter type	Difference in LS Mean
Point estimate	0.35
Confidence interval
level	95%
sides	2-sided
lower limit	-8.92
upper limit	9.62
Notes [455] - The normal approximation to the difference in binomial proportions was used to generate 95% CI for the difference in percentage.

Secondary: Percentage of Participants with JIA ACR Clinical Remission at DB Weeks 24, 28, 32, 36, 40, 44, 48, 52: Double-blind Phase Top of page

Adverse events Top of page
Adverse events information
Timeframe for reporting adverse events	From dose 1 up to 28 days after end of study treatment (maximum duration up to 16 weeks) for OL1 and for OL2 (maximum duration up to 24 weeks), For DB (maximum duration up to 248 weeks)
Assessment type	Non-systematic
Dictionary used for adverse event reporting
Dictionary name	MedDRA
Dictionary version	v26.1
Reporting groups
Reporting group title	Tofacitinib 5mg BID OL Part 1
Reporting group description	Participants were administered tofacitinib 5 mg BID via the oral route and continued to receive a stable dose of corticosteroids during open label part 1.
Reporting group title	Tofacitinib 5mg BID OL Part 2
Reporting group description	Participants who achieved sJIA American college of rheumatology (ACR) 50 response and maintained sJIA ACR 30 response for 4 weeks were administered tofacitinib 5 mg BID and tapering dose of CSs for participants treated with ˃0.2 mg/kg/day oral prednisone (or equivalent).
Reporting group title	Tofacitinib 5mg BID DB
Reporting group description	Participants who maintained a stable tapered CS dose for 4 weeks and maintained sJIA ACR 30 for 4 weeks from Part 1 and Part 2 of the open-label phase continued to receive tofacitinib 5 mg BID orally during the double-blind withdrawal phase of the study.
Reporting group title	Placebo DB
Reporting group description	Participants who maintained a stable tapered CS dose for 4 weeks and maintained sJIA ACR 30 for 4 weeks from Part 1 and Part 2 of the open-label phase were randomised to receive placebo BID orally during the double-blind withdrawal phase of the study.
Serious adverse events Tofacitinib 5mg BID OL Part 1 Tofacitinib 5mg BID OL Part 2 Tofacitinib 5mg BID DB Placebo DB Total subjects affected by serious adverse events      subjects affected / exposed 7 / 100 (7.00%) 0 / 54 (0.00%) 0 / 28 (0.00%) 2 / 31 (6.45%)      number of deaths (all causes) 0 0 0 0      number of deaths resulting from adverse events 0 0 0 0 Neoplasms benign, malignant and unspecified (incl cysts and polyps) Histiocytic necrotising lymphadenitis      subjects affected / exposed 1 / 100 (1.00%) 0 / 54 (0.00%) 0 / 28 (0.00%) 0 / 31 (0.00%)      occurrences causally related to treatment / all 1 / 1 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Hodgkin's disease      subjects affected / exposed 1 / 100 (1.00%) 0 / 54 (0.00%) 0 / 28 (0.00%) 0 / 31 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Injury, poisoning and procedural complications Overdose      subjects affected / exposed 1 / 100 (1.00%) 0 / 54 (0.00%) 0 / 28 (0.00%) 0 / 31 (0.00%)      occurrences causally related to treatment / all 1 / 1 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Immune system disorders Haemophagocytic lymphohistiocytosis      subjects affected / exposed 1 / 100 (1.00%) 0 / 54 (0.00%) 0 / 28 (0.00%) 0 / 31 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Psychiatric disorders Depression      subjects affected / exposed 1 / 100 (1.00%) 0 / 54 (0.00%) 0 / 28 (0.00%) 0 / 31 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Renal and urinary disorders Nephrolithiasis      subjects affected / exposed 0 / 100 (0.00%) 0 / 54 (0.00%) 0 / 28 (0.00%) 1 / 31 (3.23%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Musculoskeletal and connective tissue disorders Still's disease      subjects affected / exposed 3 / 100 (3.00%) 0 / 54 (0.00%) 0 / 28 (0.00%) 0 / 31 (0.00%)      occurrences causally related to treatment / all 0 / 3 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Infections and infestations Bronchitis      subjects affected / exposed 0 / 100 (0.00%) 0 / 54 (0.00%) 0 / 28 (0.00%) 1 / 31 (3.23%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 1 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0
Frequency threshold for reporting non-serious adverse events: 2%
Non-serious adverse events Tofacitinib 5mg BID OL Part 1 Tofacitinib 5mg BID OL Part 2 Tofacitinib 5mg BID DB Placebo DB Total subjects affected by non serious adverse events      subjects affected / exposed 33 / 100 (33.00%) 15 / 54 (27.78%) 23 / 28 (82.14%) 25 / 31 (80.65%) Neoplasms benign, malignant and unspecified (incl cysts and polyps) Skin papilloma      subjects affected / exposed 0 / 100 (0.00%) 0 / 54 (0.00%) 1 / 28 (3.57%) 0 / 31 (0.00%)      occurrences all number 0 0 1 0 General disorders and administration site conditions Pyrexia      subjects affected / exposed 6 / 100 (6.00%) 2 / 54 (3.70%) 4 / 28 (14.29%) 1 / 31 (3.23%)      occurrences all number 6 8 9 1 Feeling cold      subjects affected / exposed 0 / 100 (0.00%) 0 / 54 (0.00%) 1 / 28 (3.57%) 0 / 31 (0.00%)      occurrences all number 0 0 1 0 Condition aggravated      subjects affected / exposed 0 / 100 (0.00%) 0 / 54 (0.00%) 1 / 28 (3.57%) 0 / 31 (0.00%)      occurrences all number 0 0 1 0 Respiratory, thoracic and mediastinal disorders Cough      subjects affected / exposed 3 / 100 (3.00%) 0 / 54 (0.00%) 1 / 28 (3.57%) 0 / 31 (0.00%)      occurrences all number 3 0 1 0 Nasal obstruction      subjects affected / exposed 0 / 100 (0.00%) 0 / 54 (0.00%) 0 / 28 (0.00%) 1 / 31 (3.23%)      occurrences all number 0 0 0 1 Upper-airway cough syndrome      subjects affected / exposed 0 / 100 (0.00%) 0 / 54 (0.00%) 0 / 28 (0.00%) 1 / 31 (3.23%)      occurrences all number 0 0 0 1 Rhinorrhoea      subjects affected / exposed 0 / 100 (0.00%) 0 / 54 (0.00%) 0 / 28 (0.00%) 1 / 31 (3.23%)      occurrences all number 0 0 0 2 Oropharyngeal pain      subjects affected / exposed 0 / 100 (0.00%) 0 / 54 (0.00%) 1 / 28 (3.57%) 0 / 31 (0.00%)      occurrences all number 0 0 1 0 Psychiatric disorders Anxiety      subjects affected / exposed 0 / 100 (0.00%) 0 / 54 (0.00%) 0 / 28 (0.00%) 1 / 31 (3.23%)      occurrences all number 0 0 0 1 Restlessness      subjects affected / exposed 0 / 100 (0.00%) 0 / 54 (0.00%) 1 / 28 (3.57%) 0 / 31 (0.00%)      occurrences all number 0 0 1 0 Investigations Alanine aminotransferase increased      subjects affected / exposed 0 / 100 (0.00%) 0 / 54 (0.00%) 0 / 28 (0.00%) 1 / 31 (3.23%)      occurrences all number 0 0 0 1 Aspartate aminotransferase increased      subjects affected / exposed 0 / 100 (0.00%) 0 / 54 (0.00%) 0 / 28 (0.00%) 1 / 31 (3.23%)      occurrences all number 0 0 0 1 Blood creatine phosphokinase increased      subjects affected / exposed 0 / 100 (0.00%) 0 / 54 (0.00%) 1 / 28 (3.57%) 1 / 31 (3.23%)      occurrences all number 0 0 1 1 Blood urine present      subjects affected / exposed 0 / 100 (0.00%) 0 / 54 (0.00%) 1 / 28 (3.57%) 0 / 31 (0.00%)      occurrences all number 0 0 1 0 Eosinophil count increased      subjects affected / exposed 0 / 100 (0.00%) 0 / 54 (0.00%) 1 / 28 (3.57%) 0 / 31 (0.00%)      occurrences all number 0 0 1 0 Gamma-glutamyltransferase increased      subjects affected / exposed 0 / 100 (0.00%) 0 / 54 (0.00%) 0 / 28 (0.00%) 1 / 31 (3.23%)      occurrences all number 0 0 0 1 Haemoglobin decreased      subjects affected / exposed 0 / 100 (0.00%) 0 / 54 (0.00%) 2 / 28 (7.14%) 0 / 31 (0.00%)      occurrences all number 0 0 2 0 Hepatic enzyme increased      subjects affected / exposed 0 / 100 (0.00%) 0 / 54 (0.00%) 0 / 28 (0.00%) 1 / 31 (3.23%)      occurrences all number 0 0 0 1 Red blood cell count increased      subjects affected / exposed 0 / 100 (0.00%) 0 / 54 (0.00%) 1 / 28 (3.57%) 0 / 31 (0.00%)      occurrences all number 0 0 1 0 Monocyte count increased      subjects affected / exposed 0 / 100 (0.00%) 0 / 54 (0.00%) 1 / 28 (3.57%) 0 / 31 (0.00%)      occurrences all number 0 0 1 0 Mean cell volume increased      subjects affected / exposed 0 / 100 (0.00%) 0 / 54 (0.00%) 1 / 28 (3.57%) 0 / 31 (0.00%)      occurrences all number 0 0 1 0 Transaminases increased      subjects affected / exposed 0 / 100 (0.00%) 0 / 54 (0.00%) 1 / 28 (3.57%) 0 / 31 (0.00%)      occurrences all number 0 0 1 0 White blood cell count increased      subjects affected / exposed 0 / 100 (0.00%) 0 / 54 (0.00%) 1 / 28 (3.57%) 0 / 31 (0.00%)      occurrences all number 0 0 1 0 White blood cells urine positive      subjects affected / exposed 0 / 100 (0.00%) 0 / 54 (0.00%) 1 / 28 (3.57%) 0 / 31 (0.00%)      occurrences all number 0 0 1 0 Injury, poisoning and procedural complications Tibia fracture      subjects affected / exposed 0 / 100 (0.00%) 0 / 54 (0.00%) 1 / 28 (3.57%) 0 / 31 (0.00%)      occurrences all number 0 0 1 0 Skin laceration      subjects affected / exposed 0 / 100 (0.00%) 0 / 54 (0.00%) 1 / 28 (3.57%) 0 / 31 (0.00%)      occurrences all number 0 0 1 0 Skin abrasion      subjects affected / exposed 0 / 100 (0.00%) 0 / 54 (0.00%) 1 / 28 (3.57%) 0 / 31 (0.00%)      occurrences all number 0 0 1 0 Radius fracture      subjects affected / exposed 0 / 100 (0.00%) 0 / 54 (0.00%) 0 / 28 (0.00%) 1 / 31 (3.23%)      occurrences all number 0 0 0 1 Limb injury      subjects affected / exposed 0 / 100 (0.00%) 0 / 54 (0.00%) 1 / 28 (3.57%) 0 / 31 (0.00%)      occurrences all number 0 0 1 0 Ligament sprain      subjects affected / exposed 0 / 100 (0.00%) 0 / 54 (0.00%) 1 / 28 (3.57%) 0 / 31 (0.00%)      occurrences all number 0 0 1 0 Fall      subjects affected / exposed 0 / 100 (0.00%) 0 / 54 (0.00%) 2 / 28 (7.14%) 0 / 31 (0.00%)      occurrences all number 0 0 2 0 Contusion      subjects affected / exposed 0 / 100 (0.00%) 2 / 54 (3.70%) 1 / 28 (3.57%) 0 / 31 (0.00%)      occurrences all number 0 2 1 0 Nervous system disorders Headache      subjects affected / exposed 0 / 100 (0.00%) 0 / 54 (0.00%) 1 / 28 (3.57%) 1 / 31 (3.23%)      occurrences all number 0 0 1 10 Febrile convulsion      subjects affected / exposed 0 / 100 (0.00%) 0 / 54 (0.00%) 0 / 28 (0.00%) 1 / 31 (3.23%)      occurrences all number 0 0 0 1 Blood and lymphatic system disorders Anaemia      subjects affected / exposed 0 / 100 (0.00%) 0 / 54 (0.00%) 0 / 28 (0.00%) 1 / 31 (3.23%)      occurrences all number 0 0 0 1 Neutropenia      subjects affected / exposed 0 / 100 (0.00%) 0 / 54 (0.00%) 0 / 28 (0.00%) 1 / 31 (3.23%)      occurrences all number 0 0 0 2 Thrombocytosis      subjects affected / exposed 0 / 100 (0.00%) 0 / 54 (0.00%) 1 / 28 (3.57%) 0 / 31 (0.00%)      occurrences all number 0 0 1 0 Eye disorders Refraction disorder      subjects affected / exposed 0 / 100 (0.00%) 0 / 54 (0.00%) 0 / 28 (0.00%) 1 / 31 (3.23%)      occurrences all number 0 0 0 1 Gastrointestinal disorders Vomiting      subjects affected / exposed 3 / 100 (3.00%) 0 / 54 (0.00%) 3 / 28 (10.71%) 1 / 31 (3.23%)      occurrences all number 3 0 6 1 Nausea      subjects affected / exposed 3 / 100 (3.00%) 0 / 54 (0.00%) 0 / 28 (0.00%) 0 / 31 (0.00%)      occurrences all number 4 0 0 0 Abdominal pain      subjects affected / exposed 0 / 100 (0.00%) 0 / 54 (0.00%) 1 / 28 (3.57%) 0 / 31 (0.00%)      occurrences all number 0 0 1 0 Abdominal pain upper      subjects affected / exposed 0 / 100 (0.00%) 2 / 54 (3.70%) 0 / 28 (0.00%) 1 / 31 (3.23%)      occurrences all number 0 2 0 1 Diarrhoea      subjects affected / exposed 0 / 100 (0.00%) 0 / 54 (0.00%) 1 / 28 (3.57%) 2 / 31 (6.45%)      occurrences all number 0 0 1 3 Gingival swelling      subjects affected / exposed 0 / 100 (0.00%) 0 / 54 (0.00%) 0 / 28 (0.00%) 1 / 31 (3.23%)      occurrences all number 0 0 0 1 Toothache      subjects affected / exposed 0 / 100 (0.00%) 0 / 54 (0.00%) 0 / 28 (0.00%) 1 / 31 (3.23%)      occurrences all number 0 0 0 1 Hepatobiliary disorders Hypertransaminasaemia      subjects affected / exposed 0 / 100 (0.00%) 0 / 54 (0.00%) 2 / 28 (7.14%) 0 / 31 (0.00%)      occurrences all number 0 0 2 0 Skin and subcutaneous tissue disorders Rash      subjects affected / exposed 3 / 100 (3.00%) 0 / 54 (0.00%) 0 / 28 (0.00%) 1 / 31 (3.23%)      occurrences all number 3 0 0 1 Erythema nodosum      subjects affected / exposed 0 / 100 (0.00%) 0 / 54 (0.00%) 0 / 28 (0.00%) 1 / 31 (3.23%)      occurrences all number 0 0 0 1 Musculoskeletal and connective tissue disorders Arthralgia      subjects affected / exposed 0 / 100 (0.00%) 0 / 54 (0.00%) 1 / 28 (3.57%) 1 / 31 (3.23%)      occurrences all number 0 0 1 7 Back pain      subjects affected / exposed 0 / 100 (0.00%) 0 / 54 (0.00%) 1 / 28 (3.57%) 0 / 31 (0.00%)      occurrences all number 0 0 1 0 Groin pain      subjects affected / exposed 0 / 100 (0.00%) 0 / 54 (0.00%) 0 / 28 (0.00%) 1 / 31 (3.23%)      occurrences all number 0 0 0 2 Joint range of motion decreased      subjects affected / exposed 0 / 100 (0.00%) 0 / 54 (0.00%) 0 / 28 (0.00%) 1 / 31 (3.23%)      occurrences all number 0 0 0 1 Joint swelling      subjects affected / exposed 0 / 100 (0.00%) 0 / 54 (0.00%) 0 / 28 (0.00%) 1 / 31 (3.23%)      occurrences all number 0 0 0 2 Musculoskeletal stiffness      subjects affected / exposed 0 / 100 (0.00%) 0 / 54 (0.00%) 0 / 28 (0.00%) 1 / 31 (3.23%)      occurrences all number 0 0 0 1 Myalgia      subjects affected / exposed 0 / 100 (0.00%) 0 / 54 (0.00%) 0 / 28 (0.00%) 2 / 31 (6.45%)      occurrences all number 0 0 0 2 Pain in extremity      subjects affected / exposed 0 / 100 (0.00%) 0 / 54 (0.00%) 0 / 28 (0.00%) 1 / 31 (3.23%)      occurrences all number 0 0 0 4 Still's disease      subjects affected / exposed 0 / 100 (0.00%) 3 / 54 (5.56%) 8 / 28 (28.57%) 14 / 31 (45.16%)      occurrences all number 0 4 8 14 Infections and infestations Urinary tract infection      subjects affected / exposed 3 / 100 (3.00%) 0 / 54 (0.00%) 0 / 28 (0.00%) 3 / 31 (9.68%)      occurrences all number 3 0 0 3 Upper respiratory tract infection      subjects affected / exposed 10 / 100 (10.00%) 7 / 54 (12.96%) 3 / 28 (10.71%) 5 / 31 (16.13%)      occurrences all number 11 11 11 19 Nasopharyngitis      subjects affected / exposed 6 / 100 (6.00%) 0 / 54 (0.00%) 2 / 28 (7.14%) 1 / 31 (3.23%)      occurrences all number 8 0 2 1 Influenza      subjects affected / exposed 3 / 100 (3.00%) 0 / 54 (0.00%) 0 / 28 (0.00%) 1 / 31 (3.23%)      occurrences all number 3 0 0 1 Acarodermatitis      subjects affected / exposed 0 / 100 (0.00%) 0 / 54 (0.00%) 0 / 28 (0.00%) 1 / 31 (3.23%)      occurrences all number 0 0 0 1 Roseola      subjects affected / exposed 0 / 100 (0.00%) 0 / 54 (0.00%) 1 / 28 (3.57%) 0 / 31 (0.00%)      occurrences all number 0 0 1 0 Respiratory tract infection viral      subjects affected / exposed 0 / 100 (0.00%) 0 / 54 (0.00%) 0 / 28 (0.00%) 1 / 31 (3.23%)      occurrences all number 0 0 0 2 Respiratory tract infection      subjects affected / exposed 0 / 100 (0.00%) 0 / 54 (0.00%) 0 / 28 (0.00%) 1 / 31 (3.23%)      occurrences all number 0 0 0 1 Pyoderma      subjects affected / exposed 0 / 100 (0.00%) 0 / 54 (0.00%) 1 / 28 (3.57%) 0 / 31 (0.00%)      occurrences all number 0 0 1 0 Pneumonia      subjects affected / exposed 0 / 100 (0.00%) 0 / 54 (0.00%) 1 / 28 (3.57%) 0 / 31 (0.00%)      occurrences all number 0 0 1 0 Pilonidal disease      subjects affected / exposed 0 / 100 (0.00%) 0 / 54 (0.00%) 0 / 28 (0.00%) 1 / 31 (3.23%)      occurrences all number 0 0 0 1 Pharyngotonsillitis      subjects affected / exposed 0 / 100 (0.00%) 0 / 54 (0.00%) 1 / 28 (3.57%) 0 / 31 (0.00%)      occurrences all number 0 0 1 0 Pharyngitis      subjects affected / exposed 0 / 100 (0.00%) 0 / 54 (0.00%) 0 / 28 (0.00%) 2 / 31 (6.45%)      occurrences all number 0 0 0 2 Mycoplasma infection      subjects affected / exposed 0 / 100 (0.00%) 0 / 54 (0.00%) 0 / 28 (0.00%) 1 / 31 (3.23%)      occurrences all number 0 0 0 1 Herpangina      subjects affected / exposed 0 / 100 (0.00%) 0 / 54 (0.00%) 0 / 28 (0.00%) 1 / 31 (3.23%)      occurrences all number 0 0 0 1 Gastroenteritis      subjects affected / exposed 0 / 100 (0.00%) 0 / 54 (0.00%) 0 / 28 (0.00%) 1 / 31 (3.23%)      occurrences all number 0 0 0 1 COVID-19      subjects affected / exposed 0 / 100 (0.00%) 5 / 54 (9.26%) 0 / 28 (0.00%) 2 / 31 (6.45%)      occurrences all number 0 5 0 2 Bronchitis      subjects affected / exposed 0 / 100 (0.00%) 0 / 54 (0.00%) 0 / 28 (0.00%) 2 / 31 (6.45%)      occurrences all number 0 0 0 2 Acute sinusitis      subjects affected / exposed 0 / 100 (0.00%) 0 / 54 (0.00%) 1 / 28 (3.57%) 0 / 31 (0.00%)      occurrences all number 0 0 1 0 Tonsillitis bacterial      subjects affected / exposed 0 / 100 (0.00%) 0 / 54 (0.00%) 0 / 28 (0.00%) 1 / 31 (3.23%)      occurrences all number 0 0 0 1 Metabolism and nutrition disorders Hypercholesterolaemia      subjects affected / exposed 0 / 100 (0.00%) 0 / 54 (0.00%) 1 / 28 (3.57%) 1 / 31 (3.23%)      occurrences all number 0 0 1 1 Hypertriglyceridaemia      subjects affected / exposed 0 / 100 (0.00%) 0 / 54 (0.00%) 2 / 28 (7.14%) 0 / 31 (0.00%)      occurrences all number 0 0 3 0 Iron deficiency      subjects affected / exposed 0 / 100 (0.00%) 0 / 54 (0.00%) 1 / 28 (3.57%) 0 / 31 (0.00%)      occurrences all number 0 0 2 0

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Substantial protocol amendments (globally)
Were there any global substantial amendments to the protocol? Yes
Date	Amendment
16 May 2019	Tofacitinib 10 mg BID dose will no longer be evaluated. References to the 10mg BID group and 10 mg BID dose increase at Day 14 are removed throughout the protocol.
17 Mar 2021	Participants who received previous JIA treatment with tofacitinib, baricitinib or any other JAK-inhibitor were excluded. This exclusion criterion was broadened to include any JAK-inhibitor.
21 Jul 2021	This global amendment incorporated updates to facilitate enrollment of sJIA participants who were previously treated with biological DMARDs or JAK-inhibitors.
09 Feb 2022	Discussion of the risks and benefits of using tofacitinib in the pediatric population added to the body of the protocol at the request of an ethics committee.
01 Sep 2023	This global amendment incorporated measures to further facilitate the interpretation of trial results. This included a modification to the statistical analysis. Additionally, editorial and typographic changes.
Interruptions (globally)
Were there any global interruptions to the trial? No
Limitations and caveats
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
None reported

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