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Clinical Trial Results:
Efficacy, safety and tolerability of tofacitinib for Treatment of polyarticular course juvenile idiopathic Arthritis (jia) in children and adolescent subjects

Summary
EudraCT number	2015-001438-46
Trial protocol	GB BE DE ES PL
Global end of trial date	16 May 2019

Results information
Results version number	v1(current)
This version publication date	01 Feb 2020
First version publication date	01 Feb 2020
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

A3921104

ISRCTN number

US NCT number

WHO universal trial number (UTN)

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 18007181021, ClinicalTrials.gov_Inquiries@pfizer.com

Scientific contact

Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 18007181021, ClinicalTrials.gov_Inquiries@pfizer.com

Is trial part of an agreed paediatric investigation plan (PIP)

Yes

EMA paediatric investigation plan number(s)

EMEA-000057-PIP60-10

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

16 May 2019

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

16 May 2019

Was the trial ended prematurely?

Main objective of the trial

To compare the efficacy of tofacitinib versus placebo for the treatment of signs and symptoms of JIA at Week 44/End of Study (Week 26 of the double-blind phase) as measured by the percentage of subjects with disease flare (according to PRCSG/PRINTO Disease Flare criteria) after Week 18 of the open-label run-in 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 Conference on Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed.

Background therapy

Evidence for comparator

Actual start date of recruitment

10 Jun 2016

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Argentina: 15

Country: Number of subjects enrolled

Australia: 4

Country: Number of subjects enrolled

Brazil: 20

Country: Number of subjects enrolled

Canada: 7

Country: Number of subjects enrolled

Israel: 15

Country: Number of subjects enrolled

Mexico: 12

Country: Number of subjects enrolled

Poland: 1

Country: Number of subjects enrolled

Russian Federation: 19

Country: Number of subjects enrolled

Spain: 3

Country: Number of subjects enrolled

Turkey: 14

Country: Number of subjects enrolled

Ukraine: 24

Country: Number of subjects enrolled

United Kingdom: 1

Country: Number of subjects enrolled

United States: 89

Country: Number of subjects enrolled

Belgium: 1

Worldwide total number of subjects

225

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

139

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

The study was conducted in the 14 countries from 10-Jun-2016 to 16-Jun-2019. A total of 225 subjects were enrolled.

Period 1 title

Open-Label Phase (18 Weeks)

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

Tofacitinib: Open-Label Phase

Arm description

Subjects received tofacitinib 5 milligram (mg) tablets (for subjects greater than or equal to [>=] 40 kilogram (kg) body weight) or tofacitinib 5 milliliter (mL) oral solution (for subjects less than [<] 40 kg body weight), twice daily [BID], orally for 18 weeks in open-label phase.

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

Subjects received tofacitinib 5 mg tablets or tofacitinib 5 ml oral solution.

Number of subjects in period 1	Tofacitinib: Open-Label Phase
Started	225
OLJAS	184 ^[1]
OLERA	21 ^[2]
OLPsA	20 ^[3]
OLFAS	225
Completed	185
Not completed	40
Adverse event, non-fatal	12
Protocol Deviation	4
Insufficient Clinical Response	21
Unspecified	3

Notes
[1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Subjects initially received drug for 18 weeks in open label phase.
[2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Subjects initially received drug for 18 weeks in open label phase.
[3] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Subjects initially received drug for 18 weeks in open label phase.

Period 2 title

Double Blind Phase (26 Weeks)

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

Tofacitinib: Double Blind Phase

Arm description

Subjects who completed open-label phase and achieved at least a JIA ACR 30 response in open label phase, were randomized at Week 18 to receive tofacitinib tablets (for subjects >=40 body weight) or oral solution (for subjects <40 kg body weight), BID, in double-blind phase for additional 26 weeks (up to Week 44).

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

Subjects received tofacitinib 5 mg tablets or tofacitinib 5 ml oral solution.

Placebo

Arm description

Subjects who completed open-label phase and achieved at least a JIA ACR 30 response in open label phase, were randomized at Week 18 to receive placebo either as oral tablets, (for subjects >=40 body weight) or oral solution (for subjects <40 kg body weight), BID, in double-blind phase for additional 26 weeks (up to Week 44).

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

Subjects received placebo either as oral tablets or oral solution.

Number of subjects in period 2 ^[4]	Tofacitinib: Double Blind Phase	Placebo
Started	88	85
DBJAS	72	70
DBERA	9 ^[5]	7 ^[6]
DBPsA	7 ^[7]	8 ^[8]
DBSAS	88	85
Completed	61	38
Not completed	27	47
Adverse event, non-fatal	2	2
Withdrawal By Parent/Guardian	1	-
Protocol Deviation	-	1
Insufficient Clinical Response	22	44
Unspecified	1	-
Medication Error Without Associated Adverse Event	1	-

Notes
[4] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: Only, Subjects who completed open-label phase and achieved at least a JIA ACR 30 response in open label phase, were included in double blind phase.
[5] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Only those subjects who completed open-label phase and achieved at least a JIA ACR 30 response in open label phase, were included in double blind phase.
[6] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Population sets were created to show different populations based on set criteria.
[7] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Only those subjects who completed open-label phase and achieved at least a JIA ACR 30 response in open label phase, were included in double blind phase.
[8] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Population sets were created to show different populations based on set criteria.

Baseline characteristics

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Reporting group title

Open-Label Phase (18 Weeks)

Reporting group description

Subjects received tofacitinib 5 mg tablets (for Subjects >= 40 kg body weight) or tofacitinib 5 mL oral solution (for Subjects <40 kg body weight), BID, orally for 18 weeks in open-label phase.

Reporting group values	Open-Label Phase (18 Weeks)	Total
Number of subjects	225
Age categorical
Units: Subjects
Age Continuous
Units: Years
arithmetic mean (standard deviation)	11.92 ( 4.06 )	-
Sex: Female, Male
Units: Subjects
Female	169	169
Male	56	56
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	0	0
Asian	0	0
Native Hawaiian or Other Pacific Islander	0	0
Black or African American	5	5
White	196	196
More than one race	0	0
Unknown or Not Reported	24	24
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	64	64
Not Hispanic or Latino	161	161
Unknown or Not Reported	0	0

End points

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Reporting group title

Tofacitinib: Open-Label Phase

Reporting group description

Reporting group title

Tofacitinib: Double Blind Phase

Reporting group description

Reporting group title

Placebo

Reporting group description

Subject analysis set title

Tofacitinib 5mg Open Label Phase

Subject analysis set type

Full analysis

Subject analysis set description

Subjects received tofacitinib 5 mg tablets (for subjects >= 40 kg body weight) or tofacitinib 5 mL oral solution (for subjects < 40 kg body weight), BID, orally for 18 weeks in open-label phase.

Primary: Double Blind Phase: Percentage of Subjects With Disease Flare According to Pediatric Rheumatology Collaborative Study Group/Pediatric Rheumatology International Trials Organization (PRCSG/PRINTO) Disease Flare Criteria at Week 44

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End point title

Double Blind Phase: Percentage of Subjects With Disease Flare According to Pediatric Rheumatology Collaborative Study Group/Pediatric Rheumatology International Trials Organization (PRCSG/PRINTO) Disease Flare Criteria at Week 44

End point description

According to PRCSG/PRINTO, disease flare: worsening of >=30% in >=3 of 6 variables of JIA core set, with no more than 1 variable improving by >=30%. 6 core variables were: 1) Number of joints with active arthritis (joint with swelling/in absence of swelling, limited range of motion accompanied by pain/tenderness), 2) Number of joints with limited range of motion 3) Physician global evaluation of disease activity (assessed on a VAS of 0[no activity] to10 [maximum activity]), 4) Parent/legal guardian/subject global assessment of overall well-being(assessed on VAS of 0 [very well] to 10 [very poor] 5) Functional ability assessed using disability index of CHAQ: 30 questions in 8 domains (dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities), each question answered on a scale of 0=without difficulty to 3=unable to do, and 6) ESR.DBJAS: all subjects randomized to DB phase, received at least 1 dose of study medication in DB phase and had polyarticular course JIA.

End point type

Primary

End point timeframe

Week 44

End point values	Tofacitinib: Double Blind Phase	Placebo
Number of subjects analysed	72	70
Units: percentage of subjects
number (not applicable)	29.17	52.86

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

P-value

= 0.0031 ^[1]

Method

Normal approximation to the binomial

Parameter type

Difference in percentage

Point estimate

-23.69

Confidence interval

level

95%

sides

2-sided

lower limit

-39.41

upper limit

-7.97

Notes
[1] - Threshold for significance at 0.05 level.

Secondary: Double Blind Phase: Percentage of Subjects With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 50 Response at Week 44

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End point title

Double Blind Phase: Percentage of Subjects With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 50 Response at Week 44

End point description

JIA ACR50 response: >= 50% improvement in 3out of 6JIA coreset variables with no > than 1out of 6 JIA core set variables worsened by30%.6 core variables: 1)Number of joints with active arthritis (joint with swelling/in absence of swelling, limited range motion accompanied by either pain on motion/tenderness),2)Number of joints with limited range motion 3)Physician global evaluation of disease activity (VAS of 0[no activity] to 10[maximum activity]),4)Parent/legal guardian/subjects global assessment of overall well-being VAS of 0[very well] to 10[very poor] 5)Functional ability: disability index of CHAQ: 30 questions in 8domains (dressing/grooming, arising, eating, walking, hygiene, reach, grip, activities),each question answered on a scale:0=without difficulty to 3=unable to do, and, 6)ESR. DBJAS: all subjects randomized to DB phase, received at least 1 dose of study medication in DB phase and had polyarticular course JIA.

End point type

Secondary

End point timeframe

Week 44

End point values	Tofacitinib: Double Blind Phase	Placebo
Number of subjects analysed	72	70
Units: percentage of subjects
number (not applicable)	66.67	47.14

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0166 ^[2]

Method

Normal approximation to the binomial

Parameter type

Difference in percentage

Point estimate

19.52

Confidence interval

level

95%

sides

2-sided

lower limit

3.55

upper limit

35.5

Notes
[2] - Threshold for significance at 0.05 level.

Secondary: Double Blind Phase: Percentage of Subjects With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 30 Response at Week 44

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End point title

Double Blind Phase: Percentage of Subjects With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 30 Response at Week 44

End point description

JIA ACR30 response:>=30% improvement in 3 out of 6 JIA core set variables with no >than 1out of 6 JIA core set variables worsened by30%.6 core variables: 1)Number of joints with active arthritis (joint with swelling/in absence of swelling, limited range motion accompanied by either pain on motion/tenderness),2)Number of joints with limited range motion 3)Physician global evaluation of disease activity (VAS of 0[no activity] to 10[maximum activity]),4)Parent/legal guardian/subjects global assessment of overall well-being VAS of 0[very well] to 10[very poor] 5)Functional ability: disability index of CHAQ,30 questions in 8domains (dressing/grooming, arising, eating, walking, hygiene, reach, grip, activities),each question answered on a scale:0=without difficulty to 3=unable to do, and 6)ESR.DBJAS:all subjects randomized to DB phase, received at least 1 dose of study medication in DB phase and had polyarticular course JIA.

End point type

Secondary

End point timeframe

Week 44

End point values	Tofacitinib: Double Blind Phase	Placebo
Number of subjects analysed	72	70
Units: percentage of subjects
number (not applicable)	70.83	47.14

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0031 ^[3]

Method

Normal approximation to the binomial

Parameter type

Difference in percentage

Point estimate

23.69

Confidence interval

level

95%

sides

2-sided

lower limit

7.97

upper limit

39.41

Notes
[3] - Threshold for significance at 0.05 level.

Secondary: Double Blind Phase: Percentage of Subjects With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 70 Response at Week 44

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End point title

Double Blind Phase: Percentage of Subjects With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 70 Response at Week 44

End point description

JIA ACR70 response:>=70% improvement in 3out of 6 JIA core set variables with no >than 1out of 6 JIA core set variables worsened by30%.6 core variables: 1)Number of joints with active arthritis (joint with swelling/in absence of swelling, limited range motion accompanied by either pain on motion/tenderness),2)Number of joints with limited range motion 3)Physician global evaluation of disease activity (VAS of 0[no activity] to 10[maximum activity]),4)Parent/legal guardian/subjects global assessment of overall well-being VAS of 0[very well] to 10[very poor] 5)Functional ability: disability index of CHAQ: 30 questions in 8domains (dressing/grooming, arising, eating, walking, hygiene, reach, grip, activities),each question answered on a scale:0=without difficulty to 3=unable to do, and, 6)ESR. DBJAS: all subjects randomized to DB phase, received at least 1 dose of study medication in DB phase and had polyarticular course JIA.

End point type

Secondary

End point timeframe

Week 44

End point values	Tofacitinib: Double Blind Phase	Placebo
Number of subjects analysed	72	70
Units: percentage of subjects
number (not applicable)	54.17	37.14

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0387 ^[4]

Method

Normal approximation to the binomial

Parameter type

Difference in percentage

Point estimate

17.02

Confidence interval

level

95%

sides

2-sided

lower limit

0.88

upper limit

33.17

Notes
[4] - Threshold for significance at 0.05 level.

Secondary: Double Blind Phase: JIA ACR Core Variable- Change from Double-Blind Baseline in Childhood Health Assessment Questionnaire (CHAQ)- Disability Index at Week 44

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End point title

Double Blind Phase: JIA ACR Core Variable- Change from Double-Blind Baseline in Childhood Health Assessment Questionnaire (CHAQ)- Disability Index at Week 44

End point description

CHAQ comprises of 3 indices: Disability, Discomfort, and global assessment of arthritis (overall well-being). CHAQ Disability Index: measure of functional ability, consists of 30 questions in 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, activities-distributed, among a total of 30 items. Each question rated on a 4-point scale ranges from 0 (no difficulty) to 3 (unable to do). To calculate overall score, subject must have domain score in at least 6 of 8 domains. Scores of 8 domains were averaged to calculate the CHAQ disability index which ranges from 0 (no or minimal physical dysfunction) to 3 (very severe physical dysfunction), higher score=less ability. Highest score = score for functional area, minimum score = functional area is 2. DBJAS: all subjects randomized to DB phase, received at least 1 dose of study medication in DB phase and had polyarticular course JIA. Number of subjects analysed=subjects who were evaluable for this end point.

End point type

Secondary

End point timeframe

Baseline, Week 44

End point values	Tofacitinib: Double Blind Phase	Placebo
Number of subjects analysed	49	33
Units: units on a scale
least squares mean (standard error)	-0.09 ( 0.04 )	0.03 ( 0.04 )

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

In order to preserve type I error, each endpoint assessed sequentially using gate-keeping or step-down approach where statistical significance was claimed for the second endpoint only if the first endpoint in the sequence meets the requirements for significance. Analysis was based on MMRM with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the Double-Blind baseline value.

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0292 ^[5]

Method

MMRM

Parameter type

Ls mean difference

Point estimate

-0.12

Confidence interval

level

95%

sides

2-sided

lower limit

-0.22

upper limit

-0.01

Variability estimate

Standard error of the mean

Dispersion value

0.05

Notes
[5] - Threshold for significance at 0.05 level.

Secondary: Open-Label Phase: Percentage of Subjects With Disease Flare According to Pediatric Rheumatology Collaborative Study Group/Pediatric Rheumatology International Trials Organization (PRCSG/PRINTO) Disease Flare criteria at Week 2, 4, 8, 12 and 18

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End point title

Open-Label Phase: Percentage of Subjects With Disease Flare According to Pediatric Rheumatology Collaborative Study Group/Pediatric Rheumatology International Trials Organization (PRCSG/PRINTO) Disease Flare criteria at Week 2, 4, 8, 12 and 18

End point description

PRCSG/PRINTO,disease flare: worsening of >=30% in >=3 of 6 variables of JIAcore set, with no >1variable improving by >=30%.6 core variables:1)Number of joints with active arthritis (joint with swelling/absence of swelling,limited range of motion accompanied by pain/tenderness), 2)Number of joints with limited range of motion 3)Physician global evaluation of disease activity (VAS of 0[no activity] to 10[maximum activity]), 4)Parent/legal guardian/subject global assessment of overall well-being (VAS of 0[very well] to 10[very poor] 5)Functional ability assessed using disability index of CHAQ: 30 questions in 8 domains (dressing/grooming, arising, eating, walking, hygiene, reach,grip and activities),each question answered on scale of 0=without difficulty to 3=unable to do, and 6)ESR.OLJAS: all subjects who enrolled in OL phase of study and received at least 1 dose of medication in OL phase and had polyarticular courseJIA.n =subjects evaluable for this end point at specified time points.

End point type

Secondary

End point timeframe

Weeks 2, 4, 8, 12 and 18

End point values	Tofacitinib: Open-Label Phase
Number of subjects analysed	184
Units: percentage of subjects
number (not applicable)
Week 2 (n= 184)	0.54
Week 4 (n= 183)	3.83
Week 8 (n= 175)	5.14
Week 12 (n= 166)	7.23
Week 18 (n= 154)	8.44

No statistical analyses for this end point

Secondary: Double Blind Phase: Percentage of Subjects According to Pediatric Rheumatology Collaborative Study Group/Pediatric Rheumatology International Trials Organization (PRCSG/PRINTO) Disease Flare Criteria With Disease Flare at Weeks 20, 24, 28, 32, 36 and 40

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End point title

Double Blind Phase: Percentage of Subjects According to Pediatric Rheumatology Collaborative Study Group/Pediatric Rheumatology International Trials Organization (PRCSG/PRINTO) Disease Flare Criteria With Disease Flare at Weeks 20, 24, 28, 32, 36 and 40

End point description

PRCSG/PRINTO, disease flare: worsening of >=30% in >=3 of 6 variables of JIA core set, with no >1 variable improving by >=30%.6 core variables: 1)Number of joints with active arthritis (joint with swelling/absence of swelling, limited range of motion accompanied by pain/tenderness), 2)Number of joints with limited range of motion 3)Physician global evaluation of disease activity (VAS of 0[no activity] to 10[maximum activity]), 4)Parent/legal guardian/subject global assessment of overall well-being (VAS of 0[very well] to 10[very poor] 5)Functional ability assessed using disability index of CHAQ: 30 questions in 8 domains (dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities),each question answered on a scale of 0=without difficulty to 3=unable to do, and, 6)ESR. DBJAS: all subjects randomized to DB phase, received at least 1dose of study medication in DB phase and had polyarticular course JIA.

End point type

Secondary

End point timeframe

Weeks 20, 24, 28, 32, 36 and 40

End point values	Tofacitinib: Double Blind Phase	Placebo
Number of subjects analysed	72	70
Units: percentage of subjects
number (not applicable)
Week 20	9.72	11.43
Week 24	12.50	31.43
Week 28	18.06	37.14
Week 32	23.61	45.71
Week 36	25.00	48.57
Week 40	27.78	52.86

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 20

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.741

Method

Normal approximation to the binomial

Parameter type

Difference in percentage

Point estimate

-1.71

Confidence interval

level

95%

sides

2-sided

lower limit

-11.82

upper limit

8.41

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 24

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0052

Method

Normal approximation to the binomial

Parameter type

Difference in percentage

Point estimate

-18.93

Confidence interval

level

95%

sides

2-sided

lower limit

-32.22

upper limit

-5.64

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 28

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0093

Method

Normal approximation to the binomial

Parameter type

Difference in percentage

Point estimate

-19.09

Confidence interval

level

95%

sides

2-sided

lower limit

-33.48

upper limit

-4.7

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 32

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0045

Method

Normal approximation to the binomial

Parameter type

Difference in percentage

Point estimate

-22.1

Confidence interval

level

95%

sides

2-sided

lower limit

-37.35

upper limit

-6.86

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 36

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0027

Method

Normal approximation to the binomial

Parameter type

Difference in percentage

Point estimate

-23.57

Confidence interval

level

95%

sides

2-sided

lower limit

-38.97

upper limit

-8.17

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 40

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0016

Method

Normal approximation to the binomial

Parameter type

Difference in percentage

Point estimate

-25.08

Confidence interval

level

95%

sides

2-sided

lower limit

-40.69

upper limit

-9.47

Secondary: Open-Label Phase: Time to Disease Flare

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End point title

Open-Label Phase: Time to Disease Flare

End point description

Time to disease flare: time(days) from first dose of study drug until day of disease flare in OL phase. PRCSG/PRINTO, disease flare: worsening of >=30% in >=3 of 6 variables of JIA core set,no >1 variable improving by >=30%.6 core variables:1)Number of joints with active arthritis,2)Number of joints with limited range of motion 3)Physician global evaluation of disease activity (VAS of 0[no activity] to 10[maximum activity]), 4)Parent/legal guardian/subject global assessment of overall well-being (VAS of 0[very well] to 10[very poor] 5)Functional ability assessed by disability index of CHAQ: 30 questions in 8 domains each question answered on scale of 0=without difficulty to 3=unable to do, and, 6)ESR. OLJAS:all subjects enrolled in OL phase and received at least 1 dose of medication in OL phase with polyarticular course JIA. 99999= Median, upper and lower limits of 95% CI was not estimable due to small number of subjects with the event.

End point type

Secondary

End point timeframe

Day 1 up to week 18

End point values	Tofacitinib: Open-Label Phase
Number of subjects analysed	184
Units: days
median (confidence interval 95%)	99999 (99999 to 99999)

No statistical analyses for this end point

Secondary: Double Blind Phase: Time to Disease Flare

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End point title

Double Blind Phase: Time to Disease Flare

End point description

Time to disease flare: time(days) from first dose of study drug until day of disease flare in OL phase. PRCSG/PRINTO, disease flare: worsening of >=30% in >=3 of 6 variables of JIA core set,no >1 variable improving by >=30%.6 core variables:1)Number of joints with active arthritis,2)Number of joints with limited range of motion 3)Physician global evaluation of disease activity (VAS of 0[no activity] to 10[maximum activity]), 4)Parent/legal guardian/subject global assessment of overall well-being (VAS of 0[very well] to 10[very poor] 5)Functional ability assessed by disability index of CHAQ: 30 questions in 8 domains each question answered on scale of 0=without difficulty to 3=unable to do, and, 6)ESR. DBJAS analysis set used JIA. 99999= Tofacitinib; Median, upper and lower limits of 95% CI was not estimable due to small number of subjects with the event And Placebo; Upper limit of 95% CI was not estimable due to small number of subjets with the event.

End point type

Secondary

End point timeframe

Day 1 of Week 18 up to Week 44

End point values	Tofacitinib: Double Blind Phase	Placebo
Number of subjects analysed	72	70
Units: days
median (confidence interval 95%)	99999 (99999 to 99999)	155.0 (86.0 to 99999)

No statistical analyses for this end point

Secondary: Open-Label Phase: Percentage of Subjects With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 30 Response at Weeks 2, 4, 8, 12 and 18

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End point title

Open-Label Phase: Percentage of Subjects With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 30 Response at Weeks 2, 4, 8, 12 and 18

End point description

JIA ACR30 response:>=30% improvement in 3out of 6 JIA core set variables with no >than 1out of 6 JIA core set variables worsened by30%.6 core variables: 1)Number of joints with active arthritis (joint with swelling/in absence of swelling, limited range motion accompanied by either pain on motion/tenderness),2)Number of joints with limited range motion 3)Physician global evaluation of disease activity (VAS of 0[no activity] to 10[maximum activity]),4)Parent/legal guardian/subjects global assessment of overall well-being VAS of 0[very well] to 10[very poor] 5)Functional ability: disability index of CHAQ: 30 questions in 8domains (dressing/grooming, arising, eating, walking, hygiene, reach, grip, activities) ,each question answered on a scale:0=without difficulty to 3=unable to do, and, 6)ESR. OLJAS: all subjects enrolled in OL phase and received at least 1 dose of medication in OL phase with polyarticular course JIA.

End point type

Secondary

End point timeframe

Weeks 2, 4, 8, 12 and 18

End point values	Tofacitinib: Open-Label Phase
Number of subjects analysed	184
Units: percentage of subjects
number (not applicable)
Week 2 (n= 184)	45.11
Week 4 (n= 183)	68.31
Week 8 (n= 177)	79.66
Week 12 (n= 167)	85.63
Week 18 (n= 154)	92.21

No statistical analyses for this end point

Secondary: Double Blind Phase: Percentage of Subjects With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 30 Response at Double Blind Baseline, Week 20, 24, 28, 32, 36 and 40

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End point title

Double Blind Phase: Percentage of Subjects With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 30 Response at Double Blind Baseline, Week 20, 24, 28, 32, 36 and 40

End point description

JIA ACR30 response:>=30% improvement in 3 out of 6 JIA core set variables with no > than 1 out of 6 JIA core set variables worsened by30%.6 core variables: 1)Number of joints with active arthritis (joint with swelling/in absence of swelling, limited range motion accompanied by either pain on motion/tenderness),2)Number of joints with limited range motion 3)Physician global evaluation of disease activity (VAS of 0[no activity] to 10[maximum activity]),4)Parent/legal guardian/subjects global assessment of overall well-being VAS of 0[very well] to 10[very poor] 5)Functional ability: disability index of CHAQ: 30 questions in 8 domains (dressing/grooming, arising, eating, walking, hygiene, reach, grip, activities),each question answered on a scale:0=without difficulty to 3=unable to do, and 6)ESR. DBJAS: all subjects randomized to DB phase, received at least 1 dose of study medication in DB phase and had polyarticular course JIA.

End point type

Secondary

End point timeframe

Double Blind Baseline (Week 18), Week 20, 24, 28, 32, 36 and 40

End point values	Tofacitinib: Double Blind Phase	Placebo
Number of subjects analysed	72	70
Units: percentage of subjects
number (not applicable)
Double Blind Baseline (Week 18)	100.00	100.00
Week 20	88.89	82.86
Week 24	86.11	68.57
Week 28	80.56	61.43
Week 32	76.39	52.86
Week 36	73.61	48.57
Week 40	70.83	47.14

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 20

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.301

Method

Normal approximation to the binomial

Parameter type

Difference in percentage

Point estimate

6.03

Confidence interval

level

95%

sides

2-sided

lower limit

-5.4

upper limit

17.46

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 24

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0108

Method

Normal approximation to the binomial

Parameter type

Difference in percentage

Point estimate

17.54

Confidence interval

level

95%

sides

2-sided

lower limit

4.05

upper limit

31.03

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 28

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0103

Method

Normal approximation to the binomial

Parameter type

Difference in percentage

Point estimate

19.13

Confidence interval

level

95%

sides

2-sided

lower limit

4.51

upper limit

33.74

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 32

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0025

Method

Normal approximation to the binomial

Parameter type

Difference in percentage

Point estimate

23.53

Confidence interval

level

95%

sides

2-sided

lower limit

8.27

upper limit

38.8

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 36

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0016

Method

Normal approximation to the binomial

Parameter type

Difference in percentage

Point estimate

25.04

Confidence interval

level

95%

sides

2-sided

lower limit

9.52

upper limit

40.56

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 40

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0031

Method

Normal approximation to the binomial

Parameter type

Difference in percentage

Point estimate

23.69

Confidence interval

level

95%

sides

2-sided

lower limit

7.97

upper limit

39.41

Secondary: Open-Label Phase: Percentage of Subjects With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 50 Response at Week 2, 4, 8, 12 and 18

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End point title

Open-Label Phase: Percentage of Subjects With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 50 Response at Week 2, 4, 8, 12 and 18

End point description

JIA ACR50 response:>=50% improvement in 3 out of 6 JIA core set variables with no > 1 out of 6 JIA core set variables worsened by30%.6 core variables: 1)Number of joints with active arthritis (joint with swelling/in absence of swelling, limited range motion accompanied by either pain on motion/tenderness),2)Number of joints with limited range motion 3)Physician global evaluation of disease activity (VAS of 0[no activity] to 10[maximum activity]),4)Parent/legal guardian/subjects global assessment of overall well-being VAS of 0[very well] to 10[very poor] 5)Functional ability: disability index of CHAQ: 30 questions in 8domains (dressing/grooming, arising, eating, walking, hygiene, reach, grip, activities),each question answered on a scale:0=without difficulty to 3=unable to do, and, 6)ESR. OLJAS: all subjects enrolled in OL phase and received at least 1 dose of medication in OL phase with polyarticular course JIA. n =subjects evaluable for this end point at specified time points.

End point type

Secondary

End point timeframe

Weeks 2, 4, 8, 12 and 18

End point values	Tofacitinib: Open-Label Phase
Number of subjects analysed	184
Units: percentage of subjects
number (not applicable)
Week 2 (n= 184)	20.11
Week 4 (n= 183)	44.81
Week 8 (n= 177)	62.71
Week 12 (n= 167)	71.86
Week 18 (n= 154)	83.77

No statistical analyses for this end point

Secondary: Double Blind Phase: Percentage of Subjects With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 50 Response at Double Blind Baseline, Week 20, 24, 28, 32, 36 and 40

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End point title

Double Blind Phase: Percentage of Subjects With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 50 Response at Double Blind Baseline, Week 20, 24, 28, 32, 36 and 40

End point description

JIA ACR50 response:>=50% improvement in 3 out of 6 JIA core set variables with no > 1 out of 6 JIA core set variables worsened by30%.6 core variables: 1)Number of joints with active arthritis (joint with swelling/in absence of swelling, limited range motion accompanied by either pain on motion/tenderness),2)Number of joints with limited range motion 3)Physician global evaluation of disease activity (VAS of 0[no activity] to 10[maximum activity]),4)Parent/legal guardian/subjects global assessment of overall well-being VAS of 0[very well] to 10[very poor] 5)Functional ability: disability index of CHAQ: 30 questions in 8domains (dressing/grooming, arising, eating, walking, hygiene, reach, grip, activities),each question answered on a scale:0=without difficulty to 3=unable to do, and, 6)ESR. DBJAS: all subjects randomized to DB phase, received at least 1 dose of study medication in DB phase and had polyarticular course JIA.

End point type

Secondary

End point timeframe

Double blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36 and 40

End point values	Tofacitinib: Double Blind Phase	Placebo
Number of subjects analysed	72	70
Units: percentage of subjects
number (not applicable)
Double blind Baseline (Week 18)	90.28	91.43
Week 20	81.94	74.29
Week 24	80.56	58.57
Week 28	73.61	55.71
Week 32	69.44	44.29
Week 36	68.06	47.14
Week 40	68.06	45.71

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Double blind Baseline (Week 18)

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8119

Method

Normal approximation for binomial

Parameter type

Difference in percentage

Point estimate

-1.15

Confidence interval

level

95%

sides

2-sided

lower limit

-10.63

upper limit

8.33

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 20

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2682

Method

Normal approximation for binomial

Parameter type

Difference in percentage

Point estimate

7.66

Confidence interval

level

95%

sides

2-sided

lower limit

-5.9

upper limit

21.21

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 24

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0034

Method

Normal approximation for binomial

Parameter type

Difference in percentage

Point estimate

21.98

Confidence interval

level

95%

sides

2-sided

lower limit

7.26

upper limit

36.71

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 28

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0233

Method

Normal approximation for binomial

Parameter type

Difference in percentage

Point estimate

17.9

Confidence interval

level

95%

sides

2-sided

lower limit

2.44

upper limit

33.36

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 32

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0018

Method

Normal approximation for binomial

Parameter type

Difference in percentage

Point estimate

25.16

Confidence interval

level

95%

sides

2-sided

lower limit

9.39

upper limit

40.93

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 36

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0099

Method

Normal approximation for binomial

Parameter type

Difference in percentage

Point estimate

20.91

Confidence interval

level

95%

sides

2-sided

lower limit

5.01

upper limit

36.81

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 40

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0058

Method

Normal approximation for binomial

Parameter type

Difference in percentage

Point estimate

22.34

Confidence interval

level

95%

sides

2-sided

lower limit

6.46

upper limit

38.22

Secondary: Open-Label Phase: Percentage of Subjects With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 70 Response at Week 2, 4, 8, 12 and 18

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End point title

Open-Label Phase: Percentage of Subjects With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 70 Response at Week 2, 4, 8, 12 and 18

End point description

JIA ACR70 response:>=70% improvement in 3 out of 6 JIA core set variables with no > 1 out of 6 JIA core set variables worsened by30%.6 core variables: 1)Number of joints with active arthritis (joint with swelling/in absence of swelling, limited range motion accompanied by either pain on motion/tenderness),2)Number of joints with limited range motion 3)Physician global evaluation of disease activity (VAS of 0[no activity] to 10[maximum activity]),4)Parent/legal guardian/subjects global assessment of overall well-being VAS of 0[very well] to 10[very poor] 5)Functional ability: disability index of CHAQ: 30 questions in 8domains (dressing/grooming, arising, eating, walking, hygiene, reach, grip, activities),each question answered on a scale:0=without difficulty to 3=unable to do, and, 6)ESR. OLJAS: all subjects enrolled in OL phase and received at least 1 dose of medication in OL phase with polyarticular course JIA n =subjects evaluable for this end point at specified time points.

End point type

Secondary

End point timeframe

Weeks 2, 4, 8, 12 and 18

End point values	Tofacitinib: Open-Label Phase
Number of subjects analysed	184
Units: percentage of subjects
number (not applicable)
Week 2 (n= 184)	7.61
Week 4 (n= 183)	16.94
Week 8 (n= 177)	36.16
Week 12 (n= 167)	46.71
Week 18 (n= 154)	61.04

No statistical analyses for this end point

Secondary: Double Blind Phase: Percentage of Subjects With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 70 Response at Double Blind Baseline (Week 18), Week 20, 24, 28, 32, 36 and 40

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End point title

Double Blind Phase: Percentage of Subjects With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 70 Response at Double Blind Baseline (Week 18), Week 20, 24, 28, 32, 36 and 40

End point description

JIA ACR70 response:>=70% improvement in 3 out of 6 JIA core set variables with no > 1 out of 6 JIA core set variables worsened by30%.6 core variables: 1)Number of joints with active arthritis (joint with swelling/in absence of swelling, limited range motion accompanied by either pain on motion/tenderness),2)Number of joints with limited range motion 3)Physician global evaluation of disease activity (VAS of 0[no activity] to 10[maximum activity]),4)Parent/legal guardian/subjects global assessment of overall well-being VAS of 0[very well] to 10[very poor] 5)Functional ability: disability index of CHAQ: 30 questions in 8domains (dressing/grooming, arising, eating, walking, hygiene, reach, grip, activities),each question answered on a scale:0=without difficulty to 3=unable to do, and, 6)ESR. DBJAS: all subjects randomized to DB phase, received at least 1 dose of study medication in DB phase and had polyarticular course JIA.

End point type

Secondary

End point timeframe

Double Blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36 and 40

End point values	Tofacitinib: Double Blind Phase	Placebo
Number of subjects analysed	72	70
Units: percentage of subjects
number (not applicable)
DB Baseline Week 18	68.06	64.29
Week 20	58.33	55.71
Week 24	58.33	44.29
Week 28	54.17	47.14
Week 32	56.94	38.57
Week 36	54.17	34.29
Week 40	54.17	34.29

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Double Blind Baseline (Week 18)

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.6348

Method

Normal approximation to the binomial

Parameter type

Difference in percentage

Point estimate

3.77

Confidence interval

level

95%

sides

2-sided

lower limit

-11.79

upper limit

19.33

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 20

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7525

Method

Normal approximation to the binomial

Parameter type

Difference in percentage

Point estimate

2.62

Confidence interval

level

95%

sides

2-sided

lower limit

-13.66

upper limit

18.9

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 24

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0908

Method

Normal approximation to the binomial

Parameter type

Difference in percentage

Point estimate

14.05

Confidence interval

level

95%

sides

2-sided

lower limit

-2.23

upper limit

30.33

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 28

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4026

Method

Normal approximation to the binomial

Parameter type

Difference in percentage

Point estimate

7.02

Confidence interval

level

95%

sides

2-sided

lower limit

-9.38

upper limit

23.43

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 32

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0258

Method

Normal approximation to the binomial

Parameter type

Difference in percentage

Point estimate

18.37

Confidence interval

level

95%

sides

2-sided

lower limit

2.22

upper limit

34.52

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 36

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0149

Method

Normal approximation to the binomial

Parameter type

Difference in percentage

Point estimate

19.88

Confidence interval

level

95%

sides

2-sided

lower limit

3.88

upper limit

35.88

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 40

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0149

Method

Normal approximation to the binomial

Parameter type

Difference in percentage

Point estimate

19.88

Confidence interval

level

95%

sides

2-sided

lower limit

3.88

upper limit

35.88

Secondary: Open-Label Phase: Percentage of Subjects With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 90 Response at Week 2, 4, 8, 12 and 18

Top of page

End point title

Open-Label Phase: Percentage of Subjects With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 90 Response at Week 2, 4, 8, 12 and 18

End point description

JIA ACR90 response:>=90% improvement in 3 out of 6 JIA core set variables with no > 1 out of 6 JIA core set variables worsened by30%.6 core variables: 1)Number of joints with active arthritis (joint with swelling/in absence of swelling, limited range motion accompanied by either pain on motion/tenderness),2)Number of joints with limited range motion 3)Physician global evaluation of disease activity (VAS of 0[no activity] to 10[maximum activity]),4)Parent/legal guardian/subjects global assessment of overall well-being VAS of 0[very well] to 10[very poor] 5)Functional ability: disability index of CHAQ: 30 questions in 8domains (dressing/grooming, arising, eating, walking, hygiene, reach, grip, activities),each question answered on a scale: 0=without difficulty to 3=unable to do, and, 6)ESR. OLJAS: all subjects enrolled in OL phase and received at least 1 dose of medication in OL phase with polyarticular course JIA. n =subjects evaluable for this end point at specified time points.

End point type

Secondary

End point timeframe

Week 2, 4, 8, 12 and 18

End point values	Tofacitinib: Open-Label Phase
Number of subjects analysed	184
Units: percentage of subjects
number (not applicable)
Week 2 (n= 184)	0
Week 4 (n= 183)	3.83
Week 8 (n= 177)	11.30
Week 12 (n= 167)	20.96
Week 18 (n= 154)	33.12

No statistical analyses for this end point

Secondary: Double Blind Phase: Percentage of Subjects With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 90 Response at Double Blind Baseline, Week 20, 24, 28, 32, 36, 40 and 44

Top of page

End point title

Double Blind Phase: Percentage of Subjects With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 90 Response at Double Blind Baseline, Week 20, 24, 28, 32, 36, 40 and 44

End point description

JIA ACR90 response:>=90% improvement in 3 out of 6 JIA core set variables with no > 1 out of 6 JIA core set variables worsened by30%.6 core variables: 1)Number of joints with active arthritis (joint with swelling/in absence of swelling, limited range motion accompanied by either pain on motion/tenderness),2)Number of joints with limited range motion 3)Physician global evaluation of disease activity (VAS of 0[no activity] to 10[maximum activity]),4)Parent/legal guardian/subjects global assessment of overall well-being VAS of 0[very well] to 10[very poor] 5)Functional ability: disability index of CHAQ: 30 questions in 8domains (dressing/grooming, arising, eating, walking, hygiene, reach, grip, activities),each question answered on a scale:0=without difficulty to 3=unable to do, and, 6)ESR. DBJAS: all subjects randomized to DB phase, received at least 1 dose of study medication in DB phase and had polyarticular course JIA.

End point type

Secondary

End point timeframe

Double Blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36, 40 and 44

End point values	Tofacitinib: Double Blind Phase	Placebo
Number of subjects analysed	72	70
Units: percentage of subjects
number (not applicable)
DB Baseline (Week 18)	33.33	38.57
Week 20	34.72	25.71
Week 24	37.50	28.57
Week 28	36.11	27.14
Week 32	38.89	22.86
Week 36	38.89	20.00
Week 40	34.72	22.86
Week 44	34.72	21.43

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Double Blind Baseline (Week 18)

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.515

Method

Normal approximation to the binomial

Parameter type

Difference in percentage

Point estimate

-5.24

Confidence interval

level

95%

sides

2-sided

lower limit

-21

upper limit

10.53

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 20

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.24

Method

Normal approximation to the binomial

Parameter type

Difference in percentage

Point estimate

9.01

Confidence interval

level

95%

sides

2-sided

lower limit

-6.02

upper limit

24.03

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 24

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2557

Method

Normal approximation to the binomial

Parameter type

Difference in percentage

Point estimate

8.93

Confidence interval

level

95%

sides

2-sided

lower limit

-6.47

upper limit

24.32

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 28

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2481

Method

Normal approximation to the binomial

Parameter type

Difference in percentage

Point estimate

8.97

Confidence interval

level

95%

sides

2-sided

lower limit

-6.25

upper limit

24.19

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 32

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0356

Method

Normal approximation to the binomial

Parameter type

Difference in percentage

Point estimate

16.03

Confidence interval

level

95%

sides

2-sided

lower limit

1.08

upper limit

30.98

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 36

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0115

Method

Normal approximation to the binomial

Parameter type

Difference in percentage

Point estimate

18.89

Confidence interval

level

95%

sides

2-sided

lower limit

4.24

upper limit

33.54

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 40

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.115

Method

Normal approximation to the binomial

Parameter type

Difference in percentage

Point estimate

11.87

Confidence interval

level

95%

sides

2-sided

lower limit

-2.89

upper limit

26.62

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 44

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0744

Method

Normal approximation to the binomial

Parameter type

Difference in percentage

Point estimate

13.29

Confidence interval

level

95%

sides

2-sided

lower limit

-1.31

upper limit

27.9

Secondary: Open-Label Phase: Percentage of Subjects With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 100 Response at Week 2, 4, 8, 12 and 18

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End point title

Open-Label Phase: Percentage of Subjects With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 100 Response at Week 2, 4, 8, 12 and 18

End point description

JIA ACR100 response:>=100% improvement in 3 out of 6 JIA core set variables with no > 1 out of 6 JIA core set variables worsened by30%.6 core variables: 1)Number of joints with active arthritis (joint with swelling/in absence of swelling, limited range motion accompanied by either pain on motion/tenderness),2)Number of joints with limited range motion 3)Physician global evaluation of disease activity (VAS of 0[no activity] to 10[maximum activity]),4)Parent/legal guardian/subjects global assessment of overall well-being VAS of 0[very well] to 10[very poor] 5)Functional ability: disability index of CHAQ: 30 questions in 8domains (dressing/grooming, arising, eating, walking, hygiene, reach, grip, activities),each question answered on a scale:0=without difficulty to 3=unable to do, and, 6)ESR. OLJAS:all subjects enrolled in OL phase and received at least 1 dose of medication in OL phase with polyarticular course JIA.

End point type

Secondary

End point timeframe

Weeks 2, 4, 8, 12 and 18

End point values	Tofacitinib: Open-Label Phase
Number of subjects analysed	184
Units: percentage of subjects
number (not applicable)
Week 2 (n= 184)	0.0
Week 4 (n= 183)	2.19
Week 8 (n= 177)	8.47
Week 12 (n= 167)	14.37
Week 18 (n= 154)	21.43

No statistical analyses for this end point

Secondary: Double Blind Phase: Percentage of Subjects With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 100 Response at Double Blind Baseline, Week 20, 24, 28, 32, 36, 40 and 44

Top of page

End point title

Double Blind Phase: Percentage of Subjects With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 100 Response at Double Blind Baseline, Week 20, 24, 28, 32, 36, 40 and 44

End point description

JIA ACR100 response:>=100% improvement in 3 out of 6 JIA core set variables with no >1 out of 6 JIA core set variables worsened by30%.6 core variables: 1)Number of joints with active arthritis (joint with swelling/in absence of swelling, limited range motion accompanied by either pain on motion/tenderness),2)Number of joints with limited range motion 3)Physician global evaluation of disease activity (VAS of 0[no activity] to 10[maximum activity]),4)Parent/legal guardian/subjects global assessment of overall well-being VAS of 0[very well] to 10[very poor] 5)Functional ability: disability index of CHAQ: 30 questions in 8 domains (dressing/grooming, arising, eating, walking, hygiene, reach, grip, activities),each question answered on a scale:0=without difficulty to 3=unable to do, and, 6)ESR. DBJAS: all subjects randomized to DB phase, received at least 1 dose of study medication in DB phase and had polyarticular course JIA.

End point type

Secondary

End point timeframe

Double Blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36, 40 and 44

End point values	Tofacitinib: Double Blind Phase	Placebo
Number of subjects analysed	72	70
Units: percentage of subjects
number (not applicable)
DB Baseline	15.28	31.43
Week 20	27.78	17.14
Week 24	27.78	24.29
Week 28	26.39	24.29
Week 32	27.78	21.43
Week 36	30.56	18.57
Week 40	29.17	20.00
Week 44	29.17	17.14

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Double Blind Baseline (Week 18)

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0207

Method

Normal approximation to the binomial

Parameter type

Difference in percentage

Point estimate

-16.15

Confidence interval

level

95%

sides

2-sided

lower limit

-29.84

upper limit

-2.46

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 20

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1254

Method

Normal approximation to the binomial

Parameter type

Difference in percentage

Point estimate

10.63

Confidence interval

level

95%

sides

2-sided

lower limit

-2.97

upper limit

24.24

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 24

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.635

Method

Normal approximation to the binomial

Parameter type

Difference in percentage

Point estimate

3.49

Confidence interval

level

95%

sides

2-sided

lower limit

-10.93

upper limit

17.91

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 28

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7732

Method

Normal approximation to the binomial

Parameter type

Difference in percentage

Point estimate

2.1

Confidence interval

level

95%

sides

2-sided

lower limit

-12.2

upper limit

16.41

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 32

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3782

Method

Normal approximation to the binomial

Parameter type

Difference in percentage

Point estimate

6.35

Confidence interval

level

95%

sides

2-sided

lower limit

-7.77

upper limit

20.47

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 36

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0936

Method

Normal approximation to the binomial

Parameter type

Difference in percentage

Point estimate

11.98

Confidence interval

level

95%

sides

2-sided

lower limit

-2.02

upper limit

25.99

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 40

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2017

Method

Normal approximation to the binomial

Parameter type

Difference in percentage

Point estimate

9.17

Confidence interval

level

95%

sides

2-sided

lower limit

-4.91

upper limit

23.24

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 44

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0858

Method

Normal approximation to the binomial

Parameter type

Difference in percentage

Point estimate

12.02

Confidence interval

level

95%

sides

2-sided

lower limit

-1.69

upper limit

25.74

Secondary: Open Label Phase: Change From Baseline in Juvenile Arthritis Disease Activity Score (JADAS) 27 C-Reactive Protein (CRP) Score at Week 2, 4, 8, 12 and 18

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End point title

Open Label Phase: Change From Baseline in Juvenile Arthritis Disease Activity Score (JADAS) 27 C-Reactive Protein (CRP) Score at Week 2, 4, 8, 12 and 18

End point description

JADAS-27 is a validated composite disease activity measure for JIA. JADAS-27 CRP score was derived from four components; 1) Physician global assessment of disease activity (assessed on a VAS of 0 [no activity] to 10 [maximum activity]), 2) Parent/legal guardian/subject global assessment of overall well-being (assessed on a VAS of 0 [very well] to 10 [very poor]), 3) Number of joints with active disease(defined as joint with swelling or, in absence of swelling, limited range of motion accompanied by either pain on motion or tenderness), 4) CRP (measured in milligram per liter [mg/L] and value normalized to 0 to 10 scale). The overall JADAS-27 score ranges from 0-57. A higher score indicates more disease activity. OLJAS:all subjects enrolled in OL phase and received at least 1 dose of medication in OL phase with polyarticular course JIA. Here, “n” signifies subjects evaluable for this endpoint at specified time points.

End point type

Secondary

End point timeframe

Baseline, Weeks 2, 4, 8, 12 and 18

End point values	Tofacitinib: Open-Label Phase
Number of subjects analysed	184
Units: Score on scale
arithmetic mean (standard deviation)
Week 2 (n= 181)	-6.35 ( 5.44 )
Week 4 (n= 180)	-9.89 ( 6.54 )
Week 8 (n= 175)	-12.47 ( 7.51 )
Week 12 (n= 163)	-14.33 ( 6.96 )
Week 18 (n= 153)	-15.80 ( 7.12 )

No statistical analyses for this end point

Secondary: Double Blind Phase: Change from Double-Blind Baseline in Juvenile Arthritis Disease Activity Score (JADAS) 27 C-Reactive Protein (CRP) Score at Week 20, 24, 28, 32, 36, 40 and 44

Top of page

End point title

Double Blind Phase: Change from Double-Blind Baseline in Juvenile Arthritis Disease Activity Score (JADAS) 27 C-Reactive Protein (CRP) Score at Week 20, 24, 28, 32, 36, 40 and 44

End point description

JADAS-27 is a validated composite disease activity measure for JIA. JADAS-27 CRP score was derived from four components; 1) Physician global assessment of disease activity (assessed on a VAS of 0 [no activity] to 10 [maximum activity]), 2) Parent/legal guardian/subject global assessment of overall well-being (assessed on a VAS of 0 [very well] to 10 [very poor]), 3) Number of joints with active disease(defined as joint with swelling or, in absence of swelling, limited range of motion accompanied by either pain on motion or tenderness), 4) CRP (measured in mg/L and value normalized to 0 to 10 scale). The overall JADAS-27 score ranges from 0-57. A higher score indicates more disease activity. DBJAS: all subjects randomized to DB phase, received at least 1dose of study medication in DB phase and had polyarticular course JIA. Here, “n” signifies subjects evaluable for this endpoint at specified time points.

End point type

Secondary

End point timeframe

Double Blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36, 40 and 44

End point values	Tofacitinib: Double Blind Phase	Placebo
Number of subjects analysed	72	70
Units: Score on scale
least squares mean (standard error)
Week 20 (n= 70, 69)	0.27 ( 0.64 )	2.33 ( 0.64 )
Week 24 (n= 65, 59)	0.83 ( 0.95 )	4.46 ( 0.97 )
Week 28 (n= 63, 47)	0.51 ( 0.91 )	4.36 ( 0.97 )
Week 32 (n= 59, 43)	0.16 ( 0.73 )	3.46 ( 0.81 )
Week 36 (n= 54, 36)	0.34 ( 1.09 )	6.55 ( 1.22 )
Week 40 (n= 53, 34)	0.85 ( 1.13 )	7.11 ( 1.26 )
Week 44 (n= 49, 32)	0.03 ( 0.91 )	4.39 ( 1.00 )

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 20: Analysis was based on Mixed Model for Repeated Measures (MMRM) with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the Double-Blind baseline value.

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0088

Method

MMRM

Parameter type

LS mean difference

Point estimate

-2.07

Confidence interval

level

95%

sides

2-sided

lower limit

-3.6

upper limit

-0.53

Variability estimate

Standard error of the mean

Dispersion value

0.78

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 24: Analysis was based on MMRM with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the Double-Blind baseline value.

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0054

Method

MMRM

Parameter type

LS mean difference

Point estimate

-3.64

Confidence interval

level

95%

sides

2-sided

lower limit

-6.17

upper limit

-1.1

Variability estimate

Standard error of the mean

Dispersion value

1.28

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 28: Analysis was based on MMRM with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the Double-Blind baseline value.

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0039

Method

MMRM

Parameter type

LS mean difference

Point estimate

-3.85

Confidence interval

level

95%

sides

2-sided

lower limit

-6.38

upper limit

-1.32

Variability estimate

Standard error of the mean

Dispersion value

1.25

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 32: Analysis was based on MMRM with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the Double-Blind baseline value.

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0022

Method

MMRM

Parameter type

LS mean difference

Point estimate

-3.3

Confidence interval

level

95%

sides

2-sided

lower limit

-5.3

upper limit

-1.29

Variability estimate

Standard error of the mean

Dispersion value

0.98

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 36: Analysis was based on MMRM with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the Double-Blind baseline value.

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0005

Method

MMRM

Parameter type

LS mean difference

Point estimate

-6.21

Confidence interval

level

95%

sides

2-sided

lower limit

-9.42

upper limit

-3

Variability estimate

Standard error of the mean

Dispersion value

1.57

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 40: Analysis was based on MMRM with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the Double-Blind baseline value.

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0006

Method

MMRM

Parameter type

LS mean difference

Point estimate

-6.26

Confidence interval

level

95%

sides

2-sided

lower limit

-9.6

upper limit

-2.92

Variability estimate

Standard error of the mean

Dispersion value

1.63

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 44: Analysis was based on MMRM with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the Double-Blind baseline value.

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0027

Method

MMRM

Parameter type

LS mean difference

Point estimate

-4.36

Confidence interval

level

95%

sides

2-sided

lower limit

-7.02

upper limit

-1.71

Variability estimate

Standard error of the mean

Dispersion value

1.27

Secondary: Open Label Phase: Change From Baseline in JADAS-27 Erythrocyte Sedimentation Rate (ESR) Score at Week 2, 4, 8, 12 and 18

Top of page

End point title

Open Label Phase: Change From Baseline in JADAS-27 Erythrocyte Sedimentation Rate (ESR) Score at Week 2, 4, 8, 12 and 18

End point description

JADAS-27 is a validated composite disease activity measure for JIA. JADAS-27 ESR score was derived from four components; 1) Physician global assessment of disease activity (assessed on a VAS of 0 [no activity] to 10 [maximum activity]), 2) Parent/legal guardian/subject global assessment of overall well-being (assessed on a VAS of 0 [very well] to 10 [very poor]), 3) Number of joints with active disease (maximum of 27 and defined as joint with swelling or, in absence of swelling, limited range of motion accompanied by either pain on motion or tenderness), 4) ESR. The overall JADAS-27 score ranges from 0-57. A higher score indicates more disease activity. OLJAS: all subjects enrolled in OL phase and received at least 1 dose of medication in OL phase with polyarticular course JIA. Here, “n” signifies subjects evaluable for this endpoint at specified time points.

End point type

Secondary

End point timeframe

Baseline, Weeks 2, 4, 8, 12 and 18

End point values	Tofacitinib: Open-Label Phase
Number of subjects analysed	184
Units: Score on scale
arithmetic mean (standard deviation)
Week 2 (n= 180)	-6.38 ( 5.52 )
Week 4 (n= 180)	-10.14 ( 6.63 )
Week 8 (n= 174)	-12.60 ( 7.60 )
Week 12 (n= 165)	-14.54 ( 6.90 )
Week 18 (n= 154)	-15.94 ( 7.17 )

No statistical analyses for this end point

Secondary: Double Blind Phase: Change from Double-Blind Baseline in JADAS-27 Erythrocyte Sedimentation Rate (ESR) Score at Week 20, 24, 28, 32, 36, 40 and 44

Top of page

End point title

Double Blind Phase: Change from Double-Blind Baseline in JADAS-27 Erythrocyte Sedimentation Rate (ESR) Score at Week 20, 24, 28, 32, 36, 40 and 44

End point description

JADAS-27 is a validated composite disease activity measure for JIA. JADAS-27 ESR score was derived from four components; 1) Physician global assessment of disease activity (assessed on a VAS of 0 [no activity] to 10 [maximum activity]), 2) Parent/legal guardian/subject global assessment of overall well-being (assessed on a VAS of 0 [very well] to 10 [very poor]), 3) Number of joints with active disease (maximum of 27 and defined as joint with swelling or, in absence of swelling, limited range of motion accompanied by either pain on motion or tenderness), 4) ESR. The overall JADAS-27 score ranges from 0-57. A higher score indicates more disease activity. DBJAS: all subjects randomized to DB phase, received at least 1dose of study medication in DB phase and had polyarticular course JIA. Here, “n” signifies subjects evaluable for this endpoint at specified time points.

End point type

Secondary

End point timeframe

Double Blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36, 40 and 44

End point values	Tofacitinib: Double Blind Phase	Placebo
Number of subjects analysed	72	70
Units: Score on scale
least squares mean (standard error)
Week 20 (n= 71, 70)	0.62 ( 0.62 )	2.45 ( 0.62 )
Week 24 (n= 66, 60)	0.92 ( 0.90 )	4.33 ( 0.92 )
Week 28 (n= 63, 49)	0.64 ( 0.86 )	4.22 ( 0.90 )
Week 32 (n= 59, 45)	0.26 ( 0.75 )	3.67 ( 0.81 )
Week 36 (n= 55, 37)	0.60 ( 1.06 )	6.26 ( 1.17 )
Week 40 (n= 53, 35)	0.73 ( 1.05 )	6.35 ( 1.15 )
Week 44 (n= 49, 33)	0.09 ( 0.91 )	4.50 ( 0.97 )

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0172

Method

MMRM

Parameter type

LS Mean Difference

Point estimate

-1.83

Confidence interval

level

95%

sides

2-sided

lower limit

-3.32

upper limit

-0.33

Variability estimate

Standard error of the mean

Dispersion value

0.76

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 24: Analysis was based on MMRM with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the Double-Blind baseline value. All MMRM models adjusted for OL baseline CRP category.

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0057

Method

MMRM

Parameter type

LS Mean Difference

Point estimate

-3.41

Confidence interval

level

95%

sides

2-sided

lower limit

-5.81

upper limit

-1.01

Variability estimate

Standard error of the mean

Dispersion value

1.21

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 28: Analysis was based on MMRM with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the Double-Blind baseline value. All MMRM models adjusted for OL baseline CRP category.

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0038

Method

MMRM

Parameter type

LS Mean Difference

Point estimate

-3.58

Confidence interval

level

95%

sides

2-sided

lower limit

-5.94

upper limit

-1.23

Variability estimate

Standard error of the mean

Dispersion value

1.16

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 32: Analysis was based on MMRM with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the Double-Blind baseline value. All MMRM models adjusted for OL baseline CRP category.

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.002

Method

MMRM

Parameter type

LS Mean Difference

Point estimate

-3.41

Confidence interval

level

95%

sides

2-sided

lower limit

-5.47

upper limit

-1.36

Variability estimate

Standard error of the mean

Dispersion value

1.01

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 36: Analysis was based on MMRM with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the Double-Blind baseline value. All MMRM models adjusted for OL baseline CRP category.

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0007

Method

MMRM

Parameter type

LS Mean Difference

Point estimate

-5.66

Confidence interval

level

95%

sides

2-sided

lower limit

-8.74

upper limit

-2.57

Variability estimate

Standard error of the mean

Dispersion value

1.52

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 40: Analysis was based on MMRM with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the Double-Blind baseline value. All MMRM models adjusted for OL baseline CRP category.

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0007

Method

MMRM

Parameter type

LS Mean Difference

Point estimate

-5.62

Confidence interval

level

95%

sides

2-sided

lower limit

-8.66

upper limit

-2.58

Variability estimate

Standard error of the mean

Dispersion value

1.49

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 44:Analysis was based on MMRM with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the Double-Blind baseline value. All MMRM models adjusted for OL baseline CRP category.

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0018

Method

MMRM

Parameter type

LS Mean Difference

Point estimate

-4.41

Confidence interval

level

95%

sides

2-sided

lower limit

-6.99

upper limit

-1.82

Variability estimate

Standard error of the mean

Dispersion value

1.25

Secondary: Open-Label Phase: Percentage of Subjects With JADAS-27 CRP Minimum Disease Activity at Week 2, 4, 8, 12 and 18

Top of page

End point title

Open-Label Phase: Percentage of Subjects With JADAS-27 CRP Minimum Disease Activity at Week 2, 4, 8, 12 and 18

End point description

Minimum Disease Activity is defined by a JADAS-27 CRP score less than or equal to 3.8 for subjects with polyarthritis, and less than or equal to 2 for subjects with oligoarthritis. JADAS-27 is a validated composite disease activity measure for JIA. JADAS-27 CRP score was derived from four components; 1) Physician global assessment of disease activity (assessed on a VAS of 0 [no activity] to 10 [maximum activity]), 2) Parent/legal guardian/subject global assessment of overall well-being (assessed on a VAS of 0 [very well] to 10 [very poor]), 3) Number of joints with active disease(maximum of 27 defined as joint with swelling or, in absence of swelling, limited range of motion accompanied by either pain on motion or tenderness), 4) CRP and value normalized to 0 to 10 scale). OLJAS:all subjects enrolled in OL phase and received at least 1 dose of medication in OL phase with polyarticular course JIA. Here, “n” signifies subjects evaluable for this endpoint at specified time points.

End point type

Secondary

End point timeframe

Weeks 2, 4, 8, 12 and 18

End point values	Tofacitinib: Open-Label Phase
Number of subjects analysed	184
Units: percentage of subjects
number (not applicable)
Baseline (n= 184)	0
Week 2 (n= 183)	2.19
Week 4 (n= 183)	9.29
Week 8 (n= 176)	20.45
Week 12 (n= 165)	29.09
Week 18 (n= 154)	44.16

No statistical analyses for this end point

Secondary: Double Blind Phase: Percentage of Subjects With JADAS-27 CRP Minimum Disease Activity at Double Blind Baseline, Week 20, 24, 28, 32, 36, 40 and 44

Top of page

End point title

Double Blind Phase: Percentage of Subjects With JADAS-27 CRP Minimum Disease Activity at Double Blind Baseline, Week 20, 24, 28, 32, 36, 40 and 44

End point description

Minimum Disease Activity: JADAS-27 CRP score less than or equal to 3.8 for subjects with polyarthritis, and less than or equal to 2 for subjects with oligoarthritis.JADAS-27 CRP score was derived from four components; 1) Physician global assessment of disease activity (assessed on a VAS of 0 [no activity] to 10 [maximum activity]), 2) Parent/legal guardian/subject global assessment of overall well-being (assessed on a VAS of 0 [very well] to 10 [very poor]), 3) Number of joints with active disease(maximum of 27 defined as joint with swelling or, in absence of swelling, limited range of motion accompanied by either pain on motion or tenderness), 4) CRP. overall JADAS-27 score ranges from 0-57. A higher score indicates more disease activity. DBJAS: all subjects randomized to DB phase, received at least 1dose of study medication in DB phase and had polyarticular course JIA. Here, “n” signifies subjects evaluable for this endpoint at specified time points

End point type

Secondary

End point timeframe

Double Blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36, 40 and 44

End point values	Tofacitinib: Double Blind Phase	Placebo
Number of subjects analysed	72	70
Units: percentage of subjects
number (not applicable)
DB Baseline (n= 72, 70)	48.61	47.14
Week 20 (n= 72, 70)	45.83	35.71
Week 24 (n= 72, 70)	47.22	34.29
Week 28 (n= 72, 70)	47.22	35.71
Week 32 (n= 72, 70)	40.28	32.86
Week 36 (n= 72, 70)	44.44	30.00
Week 40 (n= 72, 70)	45.83	31.43
Week 44 (n= 70, 70)	45.71	32.86

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Double Blind Baseline (Week 18)

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.861

Method

Normal approximation to the binomial

Parameter type

Difference in percentage

Point estimate

1.47

Confidence interval

level

95%

sides

2-sided

lower limit

-14.96

upper limit

17.9

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 20

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2173

Method

Normal approximation to the binomial

Parameter type

Difference in percentage

Point estimate

10.12

Confidence interval

level

95%

sides

2-sided

lower limit

-5.96

upper limit

26.2

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 24

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1135

Method

Normal approximation to the binomial

Parameter type

Difference in percentage

Point estimate

12.94

Confidence interval

level

95%

sides

2-sided

lower limit

-3.08

upper limit

28.96

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 28

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.161

Method

Normal approximation to the binomial

Parameter type

Difference in percentage

Point estimate

11.51

Confidence interval

level

95%

sides

2-sided

lower limit

-4.58

upper limit

27.6

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 32

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3571

Method

Normal approximation to the binomial

Parameter type

Difference in percentage

Point estimate

7.42

Confidence interval

level

95%

sides

2-sided

lower limit

-8.37

upper limit

23.21

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 36

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0716

Method

Normal approximation to the binomial

Parameter type

Difference in percentage

Point estimate

14.44

Confidence interval

level

95%

sides

2-sided

lower limit

-1.27

upper limit

30.16

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 40

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0746

Method

Normal approximation to the binomial

Parameter type

Difference in percentage

Point estimate

14.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.43

upper limit

30.24

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 44

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0773

Method

Normal approximation to the binomial

Parameter type

Difference in percentage

Point estimate

14.37

Confidence interval

level

95%

sides

2-sided

lower limit

-1.57

upper limit

30.3

Secondary: Open-Label Phase: Percentage of Subjects With JADAS CRP Inactive Disease Activity at Week 2, 4, 8, 12 and 18

Top of page

End point title

Open-Label Phase: Percentage of Subjects With JADAS CRP Inactive Disease Activity at Week 2, 4, 8, 12 and 18

End point description

JADAS inactive disease is defined by a JADAS score less than or equal to 1. JADAS-27 Inactive Disease cutoff values are defined as: 1) Polyarthritis: Inactive Disease: <=1 and 2) Oligoarthritis (<4 active joints): Inactive Disease: <=1. Investigation of JADAS-27 score based on investigators and parent/legal/subjects assessment. OLJAS:all subjects enrolled in OL phase and received at least 1 dose of medication in OL phase with polyarticular course JIA. Here, “n” signifies subjects evaluable for this endpoint at specified time points.

End point type

Secondary

End point timeframe

Week 2, 4, 8, 12 and 18

End point values	Tofacitinib: Open-Label Phase
Number of subjects analysed	184
Units: percentage of subjects
number (not applicable)
Week 2 (n= 183)	0
Week 4 (n= 183)	0
Week 8 (n= 176)	2.84
Week 12 (n= 165)	3.64
Week 18 (n= 154)	7.79

No statistical analyses for this end point

Secondary: Double Blind Phase: Percentage of Subjects With JADAS CRP Inactive Disease Activity at Double Blind Baseline, Week 20, 24, 28, 32, 36, 40 and 44

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End point title

Double Blind Phase: Percentage of Subjects With JADAS CRP Inactive Disease Activity at Double Blind Baseline, Week 20, 24, 28, 32, 36, 40 and 44

End point description

JADAS inactive disease is defined by a JADAS score less than or equal to 1. JADAS-27 Inactive Disease cutoff values are defined as: 1) Polyarthritis: Inactive Disease: <=1 and 2) Oligoarthritis (<4 active joints): Inactive Disease: <=1. Investigation of JADAS-27 score based on investigators and parent/legal/subjects assessment. DBJAS: all subjects randomized to DB phase, received at least 1dose of study medication in DB phase and had polyarticular course JIA.

End point type

Secondary

End point timeframe

Double Blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36, 40 and 44

End point values	Tofacitinib: Double Blind Phase	Placebo
Number of subjects analysed	72	70
Units: percentage of subjects
number (not applicable)
DB Baseline	6.94	10.00
Week 20	9.72	2.86
Week 24	12.50	5.71
Week 28	9.72	7.14
Week 32	11.11	5.71
Week 36	16.67	7.14
Week 40	18.06	7.14
Week 44	18.06	10.00

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Double Blind Baseline (Week 18)

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5131

Method

Normal approximation to the binomial

Parameter type

Difference in percentage

Point estimate

-3.06

Confidence interval

level

95%

sides

2-sided

lower limit

-12.21

upper limit

6.1

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 20

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0876

Method

Normal approximation to the binomial

Parameter type

Difference in percentage

Point estimate

6.87

Confidence interval

level

95%

sides

2-sided

lower limit

-1.01

upper limit

14.74

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 24

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1561

Method

Normal approximation to the binomial

Parameter type

Difference in percentage

Point estimate

6.79

Confidence interval

level

95%

sides

2-sided

lower limit

-2.59

upper limit

16.16

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 28

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5795

Method

Normal approximation to the binomial

Parameter type

Difference in percentage

Point estimate

2.58

Confidence interval

level

95%

sides

2-sided

lower limit

-6.54

upper limit

11.7

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 32

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2435

Method

Normal approximation to the binomial

Parameter type

Difference in percentage

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-3.67

upper limit

14.47

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 36

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0758

Method

Normal approximation to the binomial

Parameter type

Difference in percentage

Point estimate

9.52

Confidence interval

level

95%

sides

2-sided

lower limit

-0.99

upper limit

20.04

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 40

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0464

Method

Normal approximation to the binomial

Parameter type

Difference in percentage

Point estimate

10.91

Confidence interval

level

95%

sides

2-sided

lower limit

0.17

upper limit

21.65

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 44

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1634

Method

Normal approximation to the binomial

Parameter type

Difference in percentage

Point estimate

8.06

Confidence interval

level

95%

sides

2-sided

lower limit

-3.27

upper limit

19.38

Secondary: Double Blind Phase: Percentage of Subjects With JIA ACR Inactive Disease at Week 20, 24, 28, 32, 36, 40 and 44

Top of page

End point title

Double Blind Phase: Percentage of Subjects With JIA ACR Inactive Disease at Week 20, 24, 28, 32, 36, 40 and 44

End point description

JIA ACR Inactive Disease criteria included: No joints with active arthritis, No fever, rash, serositis, splenomegaly, hepatomegaly, or generalized lymphadenopathy attributable to sJIA, No active uveitis (as defined by the SUN Working Group), Normal ESR (within normal limits of the method used where tested) or, if elevated, not attributable to JIA, Physician global assessment of disease activity (assessed on a VAS of 0 [no activity] to 10 [maximum activity]) score of ‘best possible’ on the scale used, morning stiffness of <= 15 minutes. DBJAS: all subjects randomized to DB phase, received at least 1dose of study medication in DB phase and had polyarticular course JIA.

End point type

Secondary

End point timeframe

Weeks 20, 24, 28, 32, 36, 40 and 44

End point values	Tofacitinib: Double Blind Phase	Placebo
Number of subjects analysed	72	70
Units: percentage of subjects
number (not applicable)
Week 20 (n= 71, 70)	15.28	15.71
Week 24	20.83	21.43
Week 28	19.44	18.57
Week 32	22.22	20.00
Week 36	26.39	17.14
Week 40	26.39	14.29
Week 44	26.39	17.14
Double Blind Baseline (Week 18)	9.72	27.14

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 18

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0062

Method

Normal approximation to the binomial

Parameter type

Difference in percentage

Point estimate

-17.42

Confidence interval

level

95%

sides

2-sided

lower limit

-29.88

upper limit

-4.96

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 20

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9427

Method

Normal approximation to the binomial

Parameter type

Difference in percentage

Point estimate

-0.44

Confidence interval

level

95%

sides

2-sided

lower limit

-12.34

upper limit

11.47

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 24

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9308

Method

Normal approximation to the binomial

Parameter type

Difference in percentage

Point estimate

-0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-14.03

upper limit

12.84

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 28

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8945

Method

Normal approximation to the binomial

Parameter type

Difference in percentage

Point estimate

0.87

Confidence interval

level

95%

sides

2-sided

lower limit

-12.03

upper limit

13.78

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 32

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7455

Method

Normal approximation to the binomial

Parameter type

Difference in percentage

Point estimate

2.22

Confidence interval

level

95%

sides

2-sided

lower limit

-11.2

upper limit

15.64

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 36

Comparison groups

Placebo v Tofacitinib: Double Blind Phase

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1787

Method

Normal approximation to the binomial

Parameter type

Difference in percentage

Point estimate

9.25

Confidence interval

level

95%

sides

2-sided

lower limit

-4.23

upper limit

22.72

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 40

Comparison groups

Placebo v Tofacitinib: Double Blind Phase

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0695

Method

Normal approximation to the binomial

Parameter type

Difference in percentage

Point estimate

12.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.97

upper limit

25.17

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 44

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1787

Method

Normal approximation to the binomial

Parameter type

Difference in percentage

Point estimate

9.25

Confidence interval

level

95%

sides

2-sided

lower limit

-4.23

upper limit

22.72

Secondary: Double Blind Phase: Percentage of Subjects With Presence of JIA ACR Clinical Remission

Top of page

End point title

Double Blind Phase: Percentage of Subjects With Presence of JIA ACR Clinical Remission

End point description

JIA ACR Clinical Remission Criteria included: Clinical inactive disease for 6 months continuously while on medications for JIA. Clinical Inactive Disease criteria included: No joints with active arthritis, No fever, rash, serositis, splenomegaly, hepatomegaly, or generalized lymphadenopathy attributable to sJIA, No active uveitis (as defined by the SUN Working Group), Normal ESR (within normal limits of the method used where tested) or, if elevated, not attributable to JIA, Physician global assessment of disease activity (assessed on a VAS of 0 [no activity] to 10 [maximum activity]) score of ‘best possible’ (score of "0") on the scale used, morning stiffness of less than or equal to (<=) 15 minutes. DBJAS: all subjects randomized to DB phase, received at least 1dose of study medication in DB phase and had polyarticular course JIA.

End point type

Secondary

End point timeframe

From Week 18 up to Week 44

End point values	Tofacitinib: Double Blind Phase	Placebo
Number of subjects analysed	72	70
Units: percentage of subjects
number (not applicable)	4.17	4.29

Tofacitinib: Double Blind Phase Vs Placebo

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9719

Method

Normal approximation to the binomial

Parameter type

Difference in percentage

Point estimate

-0.12

Confidence interval

level

95%

sides

2-sided

lower limit

-6.74

upper limit

6.5

Secondary: Open Label Phase: JIA ACR Core Variable- Change From Baseline in Number of Joints With Active Arthritis at Week 2, 4, 8, 12 and 18

Top of page

End point title

Open Label Phase: JIA ACR Core Variable- Change From Baseline in Number of Joints With Active Arthritis at Week 2, 4, 8, 12 and 18

End point description

Number of joints with active arthritis defined as joint with swelling or, in absence of swelling, limited range of motion accompanied by either pain on motion or tenderness. The score range of the number of joints is from 0-71. OLJAS:all subjects enrolled in OL phase and received at least 1 dose of medication in OL phase with polyarticular course JIA. Here, “n” signifies subjects evaluable for this endpoint at specified time points.

End point type

Secondary

End point timeframe

Baseline, Weeks 2, 4, 8, 12 and 18

End point values	Tofacitinib: Open-Label Phase
Number of subjects analysed	184
Units: joints
arithmetic mean (standard deviation)
Week 2 (n= 183)	-4.54 ( 5.33 )
Week 4 (n= 181)	-7.21 ( 6.36 )
Week 8 (n= 175)	-8.62 ( 7.04 )
Week 12 (n= 166)	-9.76 ( 6.76 )
Week 18 (n= 154)	-10.29 ( 6.79 )

No statistical analyses for this end point

Secondary: Double Blind Phase: JIA ACR Core Variable- Change from Double-Blind Baseline in Number of Joints With Active Arthritis at Week 20, 24, 28, 32, 36, 40 and 44

Top of page

End point title

Double Blind Phase: JIA ACR Core Variable- Change from Double-Blind Baseline in Number of Joints With Active Arthritis at Week 20, 24, 28, 32, 36, 40 and 44

End point description

Number of joints with active arthritis defined as joint with swelling or, in absence of swelling, limited range of motion accompanied by either pain on motion or tenderness.Number of joints ranged from 0 to 71. DBJAS: all subjects randomized to DB phase, received at least 1dose of study medication in DB phase and had polyarticular course JIA. Here, “n” signifies subjects evaluable for this endpoint at specified time points.

End point type

Secondary

End point timeframe

Double Blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36, 40 and 44

End point values	Tofacitinib: Double Blind Phase	Placebo
Number of subjects analysed	72	70
Units: joints
least squares mean (standard error)
Week 20 (n= 71, 70)	0.21 ( 0.48 )	1.07 ( 0.49 )
Week 24 (n= 66, 60)	0.69 ( 0.71 )	2.11 ( 0.72 )
Week 28 (n= 63, 50)	0.46 ( 0.61 )	2.13 ( 0.64 )
Week 32 (n= 59, 45)	0.19 ( 0.48 )	1.36 ( 0.51 )
Week 36 (n= 55, 37)	0.52 ( 0.85 )	4.50 ( 0.92 )
Week 40 (n= 53, 35)	0.91 ( 0.85 )	4.48 ( 0.93 )
Week 44 (n= 49, 33)	0.55 ( 0.74 )	2.79 ( 0.77 )

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 20: The analysis was based on a MMRM with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the Double-Blind baseline value

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1595

Method

MMRM

Parameter type

LS Mean Difference

Point estimate

-0.87

Confidence interval

level

95%

sides

2-sided

lower limit

-2.08

upper limit

0.35

Variability estimate

Standard error of the mean

Dispersion value

0.61

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 24: The analysis was based on a MMRM with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the Double-Blind baseline value

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1421

Method

MMRM

Parameter type

LS Mean difference

Point estimate

-1.42

Confidence interval

level

95%

sides

2-sided

lower limit

-3.32

upper limit

0.48

Variability estimate

Standard error of the mean

Dispersion value

0.96

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 28: The analysis was based on a MMRM with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the Double-Blind baseline value

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0552

Method

MMRM

Parameter type

LS Mean difference

Point estimate

-1.66

Confidence interval

level

95%

sides

2-sided

lower limit

-3.37

upper limit

0.04

Variability estimate

Standard error of the mean

Dispersion value

0.83

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 32: The analysis was based on a MMRM with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the Double-Blind baseline value

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0822

Method

MMRM

Parameter type

LS Mean difference

Point estimate

-1.17

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

0.17

Variability estimate

Standard error of the mean

Dispersion value

0.63

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 36: The analysis was based on a MMRM with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the Double-Blind baseline value

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0041

Method

MMRM

Parameter type

LS Mean difference

Point estimate

-3.98

Confidence interval

level

95%

sides

2-sided

lower limit

-6.53

upper limit

-1.43

Variability estimate

Standard error of the mean

Dispersion value

1.22

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 40: The analysis was based on a MMRM with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the Double-Blind baseline value

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0085

Method

MMRM

Parameter type

LS Mean difference

Point estimate

-3.57

Confidence interval

level

95%

sides

2-sided

lower limit

-6.12

upper limit

-1.02

Variability estimate

Standard error of the mean

Dispersion value

1.22

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 44: The analysis was based on a MMRM with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the Double-Blind baseline value

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0384

Method

MMRM

Parameter type

LS Mean difference

Point estimate

-2.24

Confidence interval

level

95%

sides

2-sided

lower limit

-4.36

upper limit

-0.13

Variability estimate

Standard error of the mean

Dispersion value

1.03

Secondary: Open Label Phase: JIA ACR Core Variable- Change From Baseline in Number of Joints With Limited Range of Motion at Week 2, 4, 8, 12 and 18

Top of page

End point title

Open Label Phase: JIA ACR Core Variable- Change From Baseline in Number of Joints With Limited Range of Motion at Week 2, 4, 8, 12 and 18

End point description

The maximum number of joints with limitation of movement was 67 and these were defined as those in the joint assessment with ‘limitation of motion’. OLJAS:all subjects enrolled in OL phase and received at least 1 dose of medication in OL phase with polyarticular course JIA. Here, “n” signifies subjects evaluable for this endpoint at specified time points.

End point type

Secondary

End point timeframe

Baseline, Weeks 2, 4, 8, 12 and 18

End point values	Tofacitinib: Open-Label Phase
Number of subjects analysed	184
Units: joints
arithmetic mean (standard deviation)
Week 2 (n= 183)	-2.52 ( 4.21 )
Week 4 (n= 181)	-3.56 ( 5.68 )
Week 8 (n= 175)	-4.53 ( 5.65 )
Week 12 (n= 166)	-5.09 ( 5.79 )
Week 18 (n= 154)	-5.77 ( 5.82 )

No statistical analyses for this end point

Secondary: Double Blind Phase: JIA ACR Core Variable- Change From Double-Blind Baseline in Number of Joints With Limited Range of Motion at Double Blind Baseline (Week 18), Week 20, 24, 28, 32, 36, 40 and 44

Top of page

End point title

Double Blind Phase: JIA ACR Core Variable- Change From Double-Blind Baseline in Number of Joints With Limited Range of Motion at Double Blind Baseline (Week 18), Week 20, 24, 28, 32, 36, 40 and 44

End point description

The maximum number of joints with limitation of movement was 67 and these were defined as those in the joint assessment with ‘limitation of motion’. DBJAS: all subjects randomized to DB phase, received at least 1 dose of study medication in DB phase and had polyarticular course JIA. Here, “n” signifies subjects evaluable for this endpoint at specified time points.

End point type

Secondary

End point timeframe

Double Blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36, 40 and 44

End point values	Tofacitinib: Double Blind Phase	Placebo
Number of subjects analysed	72	70
Units: joints
least squares mean (standard error)
Week 20 (n= 71, 70)	0.38 ( 0.20 )	0.64 ( 0.19 )
Week 24 (n= 66, 60)	0.50 ( 0.28 )	1.19 ( 0.29 )
Week 28 (n= 63, 50)	0.68 ( 0.35 )	1.63 ( 0.37 )
Week 32 (n= 59, 45)	0.61 ( 0.32 )	1.40 ( 0.34 )
Week 36 (n= 55, 37)	0.47 ( 0.31 )	1.48 ( 0.34 )
Week 40 (n= 53, 35)	0.41 ( 0.34 )	1.49 ( 0.39 )
Week 44 (n= 49, 33)	0.38 ( 0.29 )	1.20 ( 0.34 )

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 20:Analysis was based on MMRM with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the double-blind baseline value.

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2595

Method

MMRM

Parameter type

LS Mean Difference

Point estimate

-0.26

Confidence interval

level

95%

sides

2-sided

lower limit

-0.72

upper limit

0.19

Variability estimate

Standard error of the mean

Dispersion value

0.23

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 24: Analysis was based on MMRM with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the double-blind baseline value.

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0674

Method

MMRM

Parameter type

LS Mean difference

Point estimate

-0.69

Confidence interval

level

95%

sides

2-sided

lower limit

-1.42

upper limit

0.05

Variability estimate

Standard error of the mean

Dispersion value

0.37

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 28: Analysis was based on MMRM with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the double-blind baseline value.

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.058

Method

MMRM

Parameter type

LS Mean difference

Point estimate

-0.95

Confidence interval

level

95%

sides

2-sided

lower limit

-1.93

upper limit

0.03

Variability estimate

Standard error of the mean

Dispersion value

0.49

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 32: Analysis was based on MMRM with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the double-blind baseline value.

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0751

Method

MMRM

Parameter type

LS Mean difference

Point estimate

-0.79

Confidence interval

level

95%

sides

2-sided

lower limit

-1.67

upper limit

0.08

Variability estimate

Standard error of the mean

Dispersion value

0.44

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 36: Analysis was based on MMRM with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the double-blind baseline value.

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0251

Method

MMRM

Parameter type

LS Mean difference

Point estimate

-1.01

Confidence interval

level

95%

sides

2-sided

lower limit

-1.88

upper limit

-0.13

Variability estimate

Standard error of the mean

Dispersion value

0.43

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 40: Analysis was based on MMRM with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the double-blind baseline value.

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0331

Method

MMRM

Parameter type

LS Mean difference

Point estimate

-1.08

Confidence interval

level

95%

sides

2-sided

lower limit

-2.07

upper limit

-0.09

Variability estimate

Standard error of the mean

Dispersion value

0.49

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 44: Analysis was based on MMRM with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the double-blind baseline value.

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0549

Method

MMRM

Parameter type

LS Mean difference

Point estimate

-0.82

Confidence interval

level

95%

sides

2-sided

lower limit

-1.66

upper limit

0.02

Variability estimate

Standard error of the mean

Dispersion value

0.42

Secondary: Open Label Phase: JIA ACR Core Variable- Change From Baseline in Physician Global Evaluation of Disease Activity at Week 2, 4, 8, 12 and 18

Top of page

End point title

Open Label Phase: JIA ACR Core Variable- Change From Baseline in Physician Global Evaluation of Disease Activity at Week 2, 4, 8, 12 and 18

End point description

Physician global evaluation of disease activity was measured on a VAS (in millimetres) of 0 (no activity) to 10 (maximum activity), higher score indicated more disease activity. OLJAS:all subjects enrolled in OL phase and received at least 1 dose of medication in OL phase with polyarticular course JIA. Here, “n” signifies subjects evaluable for this endpoint at specified time points.

End point type

Secondary

End point timeframe

Baseline, Weeks 2, 4, 8, 12 and 18

End point values	Tofacitinib: Open-Label Phase
Number of subjects analysed	184
Units: millimeters (mm)
arithmetic mean (standard deviation)
Week 2 (n= 183)	-1.81 ( 1.52 )
Week 4 (n= 181)	-2.78 ( 1.84 )
Week 8 (n= 175)	-3.51 ( 1.83 )
Week 12 (n= 166)	-4.04 ( 1.88 )
Week 18 (n= 154)	-4.54 ( 1.92 )

No statistical analyses for this end point

Secondary: Double Blind Phase: JIA ACR Core Variable-Change from Double-Blind Baseline in Physician Global Evaluation of Disease Activity at Week 20, 24, 28, 32, 36, 40 and 44

Top of page

End point title

Double Blind Phase: JIA ACR Core Variable-Change from Double-Blind Baseline in Physician Global Evaluation of Disease Activity at Week 20, 24, 28, 32, 36, 40 and 44

End point description

Physician global evaluation of disease activity was measured on a VAS (in millimetres) of 0 (no activity) to 10 (maximum activity), higher score indicated more disease activity. DBJAS: all subjects randomized to DB phase, received at least 1 dose of study medication in DB phase and had polyarticular course JIA. Here, “n” signifies subjects evaluable for this endpoint at specified time points.

End point type

Secondary

End point timeframe

Double Blind Baseline (Week 18), Week 20, 24, 28, 32, 36, 40 and 44

End point values	Tofacitinib: Double Blind Phase	Placebo
Number of subjects analysed	72	70
Units: mm
least squares mean (standard error)
Week 20 (n= 71, 70)	0.28 ( 0.20 )	0.82 ( 0.20 )
Week 24 (n= 66, 60)	0.24 ( 0.24 )	1.08 ( 0.24 )
Week 28 (n= 63, 50)	0.12 ( 0.21 )	0.92 ( 0.92 )
Week 32 (n= 59, 45)	-0.03 ( 0.20 )	0.86 ( 0.22 )
Week 36 (n= 55, 37)	0.14 ( 0.28 )	1.56 ( 0.32 )
Week 40 (n= 53, 35)	0.02 ( 0.28 )	1.64 ( 0.32 )
Week 44 (n= 49, 33)	-0.16 ( 0.29 )	1.42 ( 0.34 )

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 20: The analysis was based on a MMRM with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the Double-Blind baseline value

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0353

Method

MMRM

Parameter type

LS mean difference

Point estimate

-0.54

Confidence interval

level

95%

sides

2-sided

lower limit

-1.04

upper limit

-0.04

Variability estimate

Standard error of the mean

Dispersion value

0.25

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 24: The analysis was based on a MMRM with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the Double-Blind baseline value

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0094

Method

MMRM

Parameter type

LS Mean difference

Point estimate

-0.84

Confidence interval

level

95%

sides

2-sided

lower limit

-1.47

upper limit

-0.21

Variability estimate

Standard error of the mean

Dispersion value

0.32

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 28: The analysis was based on a MMRM with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the Double-Blind baseline value

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0065

Method

MMRM

Parameter type

LS Mean difference

Point estimate

-0.8

Confidence interval

level

95%

sides

2-sided

lower limit

-1.36

upper limit

-0.23

Variability estimate

Standard error of the mean

Dispersion value

0.28

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 32: The analysis was based on a MMRM with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the Double-Blind baseline value

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0018

Method

MMRM

Parameter type

LS Mean difference

Point estimate

-0.89

Confidence interval

level

95%

sides

2-sided

lower limit

-1.43

upper limit

-0.34

Variability estimate

Standard error of the mean

Dispersion value

0.27

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 36: The analysis was based on a MMRM with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the Double-Blind baseline value

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.001

Method

MMRM

Parameter type

LS Mean difference

Point estimate

-1.42

Confidence interval

level

95%

sides

2-sided

lower limit

-2.24

upper limit

-0.61

Variability estimate

Standard error of the mean

Dispersion value

0.41

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 40: The analysis was based on a MMRM with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the Double-Blind baseline value

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0002

Method

MMRM

Parameter type

LS Mean difference

Point estimate

-1.61

Confidence interval

level

95%

sides

2-sided

lower limit

-2.42

upper limit

-0.81

Variability estimate

Standard error of the mean

Dispersion value

0.4

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 44: The analysis was based on a MMRM with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the Double-Blind baseline value

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0007

Method

MMRM

Parameter type

LS Mean difference

Point estimate

-1.58

Confidence interval

level

95%

sides

2-sided

lower limit

-2.44

upper limit

-0.71

Variability estimate

Standard error of the mean

Dispersion value

0.43

Secondary: Open Label Phase: JIA ACR Core Variable- Change From Baseline in in Parent/Legal Guardian/Participant Global Evaluation of Overall Well-Being at Week 2, 4, 8, 12 and 18

Top of page

End point title

Open Label Phase: JIA ACR Core Variable- Change From Baseline in in Parent/Legal Guardian/Participant Global Evaluation of Overall Well-Being at Week 2, 4, 8, 12 and 18

End point description

Parent/legal guardian/subject global assessment of overall well-being was assessed on a 0 to 10 mm horizontal VAS, where "0" represents ‘very well’ (i.e. symptom-free and no arthritis disease activity) and "10" represents ‘very poor’ (i.e. maximum arthritis disease activity). OLJAS:all subjects enrolled in OL phase and received at least 1 dose of medication in OL phase with polyarticular course JIA. Here, “n” signifies subjects evaluable for this endpoint at specified time points.

End point type

Secondary

End point timeframe

Baseline, Weeks 2, 4, 8, 12 and 18

End point values	Tofacitinib: Open-Label Phase
Number of subjects analysed	184
Units: Score on scale
arithmetic mean (standard deviation)
Week 2 (n= 182)	-0.94 ( 1.95 )
Week 4 (n= 181)	-1.47 ( 1.92 )
Week 8 (n= 175)	-1.90 ( 2.20 )
Week 12 (n= 165)	-2.30 ( 2.15 )
Week 18 (n= 154)	-2.68 ( 2.33 )

No statistical analyses for this end point

Secondary: Double Blind Phase: JIA ACR Core Variable- Change from Double-Blind Baseline in Double-Blind Baseline in Parent/Legal Guardian/Participant Global Evaluation of Overall Well-Being at Week of Overall Well-Being at Week 20, 24, 28, 32, 36, 40 and 44

Top of page

End point title

Double Blind Phase: JIA ACR Core Variable- Change from Double-Blind Baseline in Double-Blind Baseline in Parent/Legal Guardian/Participant Global Evaluation of Overall Well-Being at Week of Overall Well-Being at Week 20, 24, 28, 32, 36, 40 and 44

End point description

Parent/legal guardian/subject global assessment of overall well-being was assessed on a 0 to 10 mm horizontal VAS, where "0" represents ‘very well’ (i.e. symptom-free and no arthritis disease activity) and "10" represents ‘very poor’ (i.e. maximum arthritis disease activity).DBJAS: all subjects randomized to DB phase, received at least 1 dose of study medication in DB phase and had polyarticular course JIA. Here, “n” signifies subjects evaluable for this endpoint at specified time points.

End point type

Secondary

End point timeframe

Double Blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36, 40 and 44

End point values	Tofacitinib: Double Blind Phase	Placebo
Number of subjects analysed	72	70
Units: Score on scale
least squares mean (standard error)
Week 20 (n= 71, 70)	-0.04 ( 0.18 )	0.38 ( 0.18 )
Week 24 (n= 66, 60)	-0.03 ( 0.22 )	0.91 ( 0.22 )
Week 28 (n= 63, 49)	-0.11 ( 0.24 )	0.72 ( 0.26 )
Week 32 (n= 59, 45)	-0.15 ( 0.24 )	0.82 ( 0.26 )
Week 36 (n= 55, 37)	-0.22 ( 0.21 )	0.31 ( 0.24 )
Week 40 (n= 53, 35)	-0.24 ( 0.24 )	0.39 ( 0.27 )
Week 44 (n= 49, 33)	-0.49 ( 0.22 )	0.24 ( 0.24 )

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 20: The analysis was based on a MMRM with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the Double-Blind baseline value

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0398

Method

MMRM

Parameter type

LS Mean Difference

Point estimate

-0.42

Confidence interval

level

95%

sides

2-sided

lower limit

-0.83

upper limit

-0.02

Variability estimate

Standard error of the mean

Dispersion value

0.2

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 24: The analysis was based on a MMRM with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the Double-Blind baseline value

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0011

Method

MMRM

Parameter type

LS Mean difference

Point estimate

-0.94

Confidence interval

level

95%

sides

2-sided

lower limit

-1.49

upper limit

-0.39

Variability estimate

Standard error of the mean

Dispersion value

0.28

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 28: The analysis was based on a MMRM with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the Double-Blind baseline value

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0131

Method

MMRM

Parameter type

LS mean difference

Point estimate

-0.82

Confidence interval

level

95%

sides

2-sided

lower limit

-1.47

upper limit

-0.18

Variability estimate

Standard error of the mean

Dispersion value

0.32

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 32: The analysis was based on a MMRM with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the Double-Blind baseline value

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0039

Method

MMRM

Parameter type

LS mean difference

Point estimate

-0.97

Confidence interval

level

95%

sides

2-sided

lower limit

-1.62

upper limit

-0.33

Variability estimate

Standard error of the mean

Dispersion value

0.32

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 36: The analysis was based on a MMRM with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the Double-Blind baseline value

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0711

Method

MMRM

Parameter type

LS mean difference

Point estimate

-0.53

Confidence interval

level

95%

sides

2-sided

lower limit

-1.1

upper limit

0.05

Variability estimate

Standard error of the mean

Dispersion value

0.29

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 40: The analysis was based on a MMRM with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the Double-Blind baseline value

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0658

Method

MMRM

Parameter type

LS mean difference

Point estimate

-0.63

Confidence interval

level

95%

sides

2-sided

lower limit

-1.3

upper limit

0.04

Variability estimate

Standard error of the mean

Dispersion value

0.34

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 44: The analysis was based on a MMRM with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the Double-Blind baseline value

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0154

Method

MMRM

Parameter type

LS mean difference

Point estimate

-0.73

Confidence interval

level

95%

sides

2-sided

lower limit

-1.31

upper limit

-0.15

Variability estimate

Standard error of the mean

Dispersion value

0.29

Secondary: Open Label Phase: JIA ACR Core Variable- Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ)- Disability Index at Week 2, 4, 8, 12 and 18

Top of page

End point title

Open Label Phase: JIA ACR Core Variable- Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ)- Disability Index at Week 2, 4, 8, 12 and 18

End point description

CHAQ: parent-administered, valid assessment of functional disability, discomfort in pediatrics with rheumatic diseases. Parents report subjects ability to perform activities in 8 domains: dressing, arising, eating, walking, hygiene, each,grip, common activities distributed in total of 30 items. Each item is scored on 4-point Likert scale: 0=no difficulty; 1=some difficulty;2=much difficulty;3=unable to do. Highest score reported for domain is score for that domain. Overall score = sum of domain scores divided by number of domains answered. Total score: 0=no difficulty to 3=extreme difficulty, higher score indicated more difficulty. OLJAS:all subjects enrolled in OL phase and received at least 1 dose of medication in OL phase with polyarticular course JIA. Here, “n” signifies subjects evaluable for this endpoint at specified time points.

End point type

Secondary

End point timeframe

Baseline, Weeks 2, 4, 8, 12 and 18

End point values	Tofacitinib: Open-Label Phase
Number of subjects analysed	184
Units: Score on scale
arithmetic mean (standard deviation)
Week 2 (n= 182)	-0.15 ( 0.41 )
Week 4 (n= 181)	-0.23 ( 0.42 )
Week 8 (n= 175)	-0.36 ( 0.46 )
Week 12 (n= 165)	-0.41 ( 0.53 )
Week 18 (n= 154)	-0.49 ( 0.57 )

No statistical analyses for this end point

Secondary: Double Blind Phase: JIA ACR Core Variable- Change from Double-Blind Baseline in Childhood Health Assessment Questionnaire (CHAQ)- Disability Index at Week 20, 24, 28, 32, 36, and 40

Top of page

End point title

Double Blind Phase: JIA ACR Core Variable- Change from Double-Blind Baseline in Childhood Health Assessment Questionnaire (CHAQ)- Disability Index at Week 20, 24, 28, 32, 36, and 40

End point description

CHAQ-DI: parent-administered, valid assessment of functional disability, discomfort in pediatrics with rheumatic diseases. Parents report participants’s ability to perform activities in 8 domains: dressing, arising, eating, walking,hygiene, each,grip,common activities distributed in total of 30 items.Each item is scored on 4-point Likert scale: 0=no difficulty;1=some difficulty;2=much difficulty;3=unable to do. Highest score reported for domain is score for that domain. The CHAQ-DI score is the sum of the domain scores divided by the number of domains that have a non-missing score and ranges from 0 (best) to 3 (worst). A higher score indicates less ability. DBJAS: all subjects randomized to DB phase, received at least 1 dose of study medication in DB phase and had polyarticular course JIA. Here, “n” signifies subjects evaluable for this endpoint at specified time points.

End point type

Secondary

End point timeframe

Double Blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36, and 40

End point values	Tofacitinib: Double Blind Phase	Placebo
Number of subjects analysed	72	70
Units: Score on scale
least squares mean (standard deviation)
Week 20 (n=71, 70 )	0.05 ( 0.04 )	0.08 ( 0.04 )
Week 24 (n= 66, 59)	0.01 ( 0.03 )	0.08 ( 0.04 )
Week 28 (n= 63, 49)	-0.01 ( 0.04 )	0.09 ( 0.04 )
Week 32 (n=59, 45)	0.01 ( 0.04 )	0.10 ( 0.05 )
Week 36 (n=55, 37)	-0.04 ( 0.04 )	0.08 ( 0.05 )
Week 40 (n= 53, 35)	-0.05 ( 0.04 )	0.06 ( 0.05 )

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 20: All MMRM models adjusted for OL baseline CRP category

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4777

Method

MMRM

Parameter type

LS Mean Difference

Point estimate

-0.03

Confidence interval

level

95%

sides

2-sided

lower limit

-0.12

upper limit

0.06

Variability estimate

Standard error of the mean

Dispersion value

0.04

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 24: The analysis was based on a MMRM with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the Double-Blind baseline value

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0779

Method

MMRM

Parameter type

LS mean difference

Point estimate

-0.07

Confidence interval

level

95%

sides

2-sided

lower limit

-0.16

upper limit

0.01

Variability estimate

Standard error of the mean

Dispersion value

0.04

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 28: The analysis was based on a MMRM with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the Double-Blind baseline value

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0324

Method

MMRM

Parameter type

LS mean difference

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.19

upper limit

-0.01

Variability estimate

Standard error of the mean

Dispersion value

0.05

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 32: The analysis was based on a MMRM with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the Double-Blind baseline value

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1061

Method

MMRM

Parameter type

LS mean difference

Point estimate

-0.09

Confidence interval

level

95%

sides

2-sided

lower limit

-0.2

upper limit

0.02

Variability estimate

Standard error of the mean

Dispersion value

0.06

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 36: The analysis was based on a MMRM with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the Double-Blind baseline value

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0572

Method

MMRM

Parameter type

LS mean difference

Point estimate

-0.12

Confidence interval

level

95%

sides

2-sided

lower limit

-0.24

upper limit

Variability estimate

Standard error of the mean

Dispersion value

0.06

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 40: The analysis was based on a MMRM with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the Double-Blind baseline value

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0689

Method

MMRM

Parameter type

LS mean difference

Point estimate

-0.11

Confidence interval

level

95%

sides

2-sided

lower limit

-0.24

upper limit

0.01

Variability estimate

Standard error of the mean

Dispersion value

0.06

Secondary: Open-Label Phase: Change From Baseline in Child Health Questionnaire (CHQ) Responses at Week 4 and Week 18

Top of page

End point title

Open-Label Phase: Change From Baseline in Child Health Questionnaire (CHQ) Responses at Week 4 and Week 18

End point description

CHQ: 50-item,14 subscale (Global health, physical functioning, social limitations: emotional, social limitations: physical, bodily pain, behavior, global behavior, mental health, self-esteem, general health, Change in health, emotional impact on parent, time impact on parent, family activities, family cohesion) parent or legal guardian assessed instrument of child’s physical, emotional, social well-being, and relative burden of disease on parents. Each subscale rated on Likert-type scale: range 0 to 100; higher scores indicate a more positive health status. Two summary scores: Physical Health, Psychosocial Health were weighted composites derived from subscale items using scoring algorithms (transformed scores); range 0 to 100: higher scores indicate more positive health status. OLJAS:all subjects enrolled in OL phase and received at least 1 dose of medication in OL phase with polyarticular course JIA. Here, “n” signifies subjects evaluable for this endpoint at specified time points.

End point type

Secondary

End point timeframe

Baseline, Week 4 and Week 18

End point values	Tofacitinib: Open-Label Phase
Number of subjects analysed	184
Units: Score on scale
arithmetic mean (standard deviation)
Week 4: Global Health (n= 171)	13.86 ( 22.40 )
Week 18: Global Health (n= 148)	21.28 ( 22.79 )
Week 4: Physical Functioning (n= 171)	11.83 ( 24.47 )
Week 18: Physical Functioning (n= 149)	21.44 ( 26.78 )
Week 4: Social Limitations: Emotional (n= 171)	8.12 ( 29.29 )
Week 18: Social Limitations: Emotional (n= 149)	14.62 ( 30.18 )
Week 4: Social Limitations: Physical (n= 171)	13.45 ( 31.12 )
Week 18: Social Limitations: Physical (n= 149)	20.81 ( 32.53 )
Week 4: Bodily Pain (n= 171)	19.42 ( 21.14 )
Week 18: Bodily Pain (n= 149)	30.60 ( 22.79 )
Week 4: Behavior (n= 171)	3.06 ( 12.86 )
Week 18: Behavior (n= 149)	5.70 ( 12.91 )
Week 4: Global Behavior (n= 171)	7.40 ( 23.27 )
Week 18: Global Behavior (n= 149)	9.30 ( 24.97 )
Week 4: Mental Health (n= 171)	6.43 ( 15.68 )
Week 18: Mental Health (n= 149)	6.74 ( 16.06 )
Week 4: Self Esteem (n= 171)	2.42 ( 19.47 )
Week 18: Self Esteem (n= 149)	8.45 ( 17.35 )
Week 4: Family Cohesion (n= 171)	2.78 ( 21.80 )
Week 18: Family Cohesion (n= 149)	3.62 ( 18.81 )
Week 4: General Health (n= 171)	4.20 ( 13.50 )
Week 18: General Health (n= 149)	7.02 ( 14.31 )
Week 4: Change in Health (n= 170)	0.86 ( 1.20 )
Week 18: Change in Health (n= 149)	1.70 ( 1.32 )
Week 4: Emotional Impact on Parent (n= 171)	9.02 ( 26.30 )
Week 18: Emotional Impact on Parent (n= 149)	15.38 ( 29.35 )
Week 4: Time Impact on Parent (n= 171)	6.17 ( 24.64 )
Week 18: Time Impact on Parent (n= 149)	9.99 ( 23.38 )
Week 4: Family Activities (n= 171)	5.19 ( 15.15 )
Week 18: Family Activities (n= 149)	9.59 ( 19.63 )
Week 4: Physical Summary Scores (n= 171)	8.12 ( 11.18 )
Week 18: Physical Summary Scores (n= 149)	13.36 ( 12.57 )
Week 4: Psychosocial Summary Scores (n= 171)	2.46 ( 8.13 )
Week 18: Psychosocial Summary Scores (n= 149)	4.20 ( 8.41 )

No statistical analyses for this end point

Secondary: Double Blind Phase: Change From Double-Blind Baseline in Child Health Questionnaire (CHQ) Responses at Week 44

Top of page

End point title

Double Blind Phase: Change From Double-Blind Baseline in Child Health Questionnaire (CHQ) Responses at Week 44

End point description

CHQ: 50-item,14 subscale (Global health, physical functioning, social limitations: emotional, social limitations: physical, bodily pain, behavior, global behavior, mental health, self-esteem, general health, Change in health, emotional impact on parent, time impact on parent, family activities, family cohesion) parent or legal guardian assessed instrument of child’s physical, emotional, social well-being, and relative burden of disease on parents. Each subscale rated on Likert-type scale: range0 to 100; higher scores indicate more positive health status. 2 summary scores:Physical Health, Psychosocial Health were weighted composites derived from subscale items using scoring algorithms (transformed scores); range 0 to 100: higher scores indicate more positive health status. DBJAS: all subjects randomized to DB phase, received at least 1 dose of study medication in DB phase and had polyarticular course JIA. “n” signifies subjects evaluable for this endpoint at specified time points.

End point type

Secondary

End point timeframe

Double-Blind Baseline (Week 18), Week 44

End point values	Tofacitinib: Double Blind Phase	Placebo
Number of subjects analysed	72	70
Units: Unit on scale
least squares mean (standard error)
Global Health (n= 49, 30)	5.46 ( 2.83 )	1.66 ( 3.72 )
Physical Functioning (n= 49, 31)	1.45 ( 3.16 )	-1.82 ( 3.92 )
Social Limitations: Emotional (n= 49, 31)	1.78 ( 3.53 )	-3.69 ( 4.36 )
Social Limitations: Physical (n= 49, 30)	-3.08 ( 4.03 )	-10.29 ( 5.04 )
Bodily Pain (n=49, 31)	6.34 ( 3.13 )	-1.91 ( 3.91 )
Behavior (n= 49, 31)	0.78 ( 2.09 )	4.20 ( 2.57 )
Global Behavior (n= 49, 31)	-2.61 ( 2.89 )	1.04 ( 3.54 )
Mental Health (n= 49, 31)	0.41 ( 2.53 )	3.88 ( 3.12 )
Self Esteem (n= 49, 31)	1.48 ( 3.29 )	0.76 ( 4.07 )
General Health (n= 49, 31)	7.91 ( 1.84 )	6.14 ( 2.26 )
Change in Health (n= 49, 31)	0.07 ( 0.10 )	0.09 ( 0.12 )
Emotional Impact on Parent (n= 49, 31)	9.55 ( 4.32 )	0.58 ( 5.35 )
Time Impact on Parent (n= 49, 30)	-3.83 ( 2.92 )	2.89 ( 3.62 )
Family Activities (n= 49, 31)	0.01 ( 2.39 )	8.61 ( 2.95 )
Family Cohesion (n= 49, 31)	6.04 ( 3.18 )	3.45 ( 3.92 )
Physical Summary (n= 49, 30)	1.67 ( 1.48 )	-1.81 ( 1.85 )
Psychosocial Summary (n= 49, 30)	0.64 ( 1.22 )	1.39 ( 1.52 )

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Global Health Subscale Standardized Score: Analysis based on MMRM with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the Double-Blind baseline value.

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3179

Method

MMRM

Parameter type

LS Mean Difference

Point estimate

3.79

Confidence interval

level

95%

sides

2-sided

lower limit

-3.72

upper limit

11.31

Variability estimate

Standard error of the mean

Dispersion value

3.77

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Physical Functioning Subscale Standardized Score: Analysis based on MMRM with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the Double-Blind baseline value.

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4452

Method

MMRM

Parameter type

LS mean difference

Point estimate

3.28

Confidence interval

level

95%

sides

2-sided

lower limit

-5.23

upper limit

11.78

Variability estimate

Standard error of the mean

Dispersion value

4.27

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Social Limitations: Emotional Subscale Standardized Score: Analysis based on MMRM with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the Double-Blind baseline value.

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2539

Method

MMRM

Parameter type

LS mean difference

Point estimate

5.47

Confidence interval

level

95%

sides

2-sided

lower limit

-4.01

upper limit

14.95

Variability estimate

Standard error of the mean

Dispersion value

4.76

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Social Limitations: Physical Subscale Standardized Score: Analysis based on MMRM with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the Double-Blind baseline value.

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1981

Method

MMRM

Parameter type

LS mean difference

Point estimate

7.22

Confidence interval

level

95%

sides

2-sided

lower limit

-3.86

upper limit

18.3

Variability estimate

Standard error of the mean

Dispersion value

5.56

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Bodily Pain Subscale Standardized Score: Analysis based on MMRM with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the Double-Blind baseline value.

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.062

Method

MMRM

Parameter type

LS mean difference

Point estimate

8.26

Confidence interval

level

95%

sides

2-sided

lower limit

-0.43

upper limit

16.94

Variability estimate

Standard error of the mean

Dispersion value

4.36

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Behavior Subscale Standardized Score: Analysis based on MMRM with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the Double-Blind baseline value.

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2291

Method

MMRM

Parameter type

LS mean difference

Point estimate

-3.43

Confidence interval

level

95%

sides

2-sided

lower limit

-9.06

upper limit

2.2

Variability estimate

Standard error of the mean

Dispersion value

2.83

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Global Behavior Subscale Standardized Score: Analysis based on MMRM with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the Double-Blind baseline value.

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.353

Method

MMRM

Parameter type

LS mean difference

Point estimate

-3.65

Confidence interval

level

95%

sides

2-sided

lower limit

-11.43

upper limit

4.13

Variability estimate

Standard error of the mean

Dispersion value

3.9

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Mental Health Subscale Standardized Score: Analysis based on MMRM with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the Double-Blind baseline value.

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3114

Method

MMRM

Parameter type

LS mean difference

Point estimate

-3.47

Confidence interval

level

95%

sides

2-sided

lower limit

-10.26

upper limit

3.32

Variability estimate

Standard error of the mean

Dispersion value

3.41

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Self Esteem Subscale Standardized Score: Analysis based on MMRM with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the Double-Blind baseline value.

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8736

Method

MMRM

Parameter type

LS mean difference

Point estimate

0.71

Confidence interval

level

95%

sides

2-sided

lower limit

-8.18

upper limit

9.61

Variability estimate

Standard error of the mean

Dispersion value

4.46

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

General Health Subscale Standardized Score: Analysis based on MMRM with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the Double-Blind baseline value.

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4778

Method

MMRM

Parameter type

LS mean difference

Point estimate

1.77

Confidence interval

level

95%

sides

2-sided

lower limit

-3.18

upper limit

6.72

Variability estimate

Standard error of the mean

Dispersion value

2.48

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Change in Health Subscale Score: Analysis based on MMRM with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the Double-Blind baseline value.

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8909

Method

MMRM

Parameter type

LS mean difference

Point estimate

-0.02

Confidence interval

level

95%

sides

2-sided

lower limit

-0.28

upper limit

0.25

Variability estimate

Standard error of the mean

Dispersion value

0.13

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Emotional Impact on Parent Subscale Standardized Score: Analysis based on MMRM with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the Double-Blind baseline value.

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.127

Method

MMRM

Parameter type

LS mean difference

Point estimate

8.97

Confidence interval

level

95%

sides

2-sided

lower limit

-2.61

upper limit

20.55

Variability estimate

Standard error of the mean

Dispersion value

5.81

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Time Impact on Parent Subscale Standardized Score: Analysis based on MMRM with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the Double-Blind baseline value.

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0944

Method

MMRM

Parameter type

LS mean difference

Point estimate

-6.72

Confidence interval

level

95%

sides

2-sided

lower limit

-14.62

upper limit

1.18

Variability estimate

Standard error of the mean

Dispersion value

3.96

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Family Activities Subscale Standardized Score: Analysis based on MMRM with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the Double-Blind baseline value.

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0095

Method

MMRM

Parameter type

LS mean difference

Point estimate

-8.6

Confidence interval

level

95%

sides

2-sided

lower limit

-15.03

upper limit

-2.17

Variability estimate

Standard error of the mean

Dispersion value

3.23

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Family Cohesion Subscale Standardized Score: Analysis based on MMRM with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the Double-Blind baseline value.

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5474

Method

MMRM

Parameter type

LS mean difference

Point estimate

2.59

Confidence interval

level

95%

sides

2-sided

lower limit

-5.96

upper limit

11.14

Variability estimate

Standard error of the mean

Dispersion value

4.29

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Physical Summary Scores: Analysis based on MMRM with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the Double-Blind baseline value.

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0902

Method

MMRM

Parameter type

LS mean difference

Point estimate

3.48

Confidence interval

level

95%

sides

2-sided

lower limit

-0.56

upper limit

7.52

Variability estimate

Standard error of the mean

Dispersion value

2.03

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Psychosocial Summary Scores: Analysis based on MMRM with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the Double-Blind baseline value.

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.6539

Method

MMRM

Parameter type

LS mean difference

Point estimate

-0.75

Confidence interval

level

95%

sides

2-sided

lower limit

-4.07

upper limit

2.57

Variability estimate

Standard error of the mean

Dispersion value

1.67

Secondary: Open Label Phase: Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ)- Discomfort Index at Week 2, 4, 8, 12 and 18

Top of page

End point title

Open Label Phase: Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ)- Discomfort Index at Week 2, 4, 8, 12 and 18

End point description

CHAQ is a validated instrument and comprises of two indices, Disability and Discomfort, and global assessment of arthritis (overall well-being). Discomfort Index included: assessment of discomfort, the parent/legal guardian/subject were asked to provide a response to the question: How much pain do you think your child had because of his or her illness in the past week?, The parent/legal guardian/ participant rated the overall pain on a 0 to 10 VAS, where ‘0’ indicates ‘No Pain’ and ‘10’ indicates ‘Very Severe Pain’, higher scores indicates more severity. OLJAS:all subjects enrolled in OL phase and received at least 1 dose of medication in OL phase with polyarticular course JIA. Here, “n” signifies subjects evaluable for this endpoint at specified time points.

End point type

Secondary

End point timeframe

Baseline, Weeks 2, 4, 8, 12 and 18

End point values	Tofacitinib: Open-Label Phase
Number of subjects analysed	184
Units: Score on scale
arithmetic mean (standard deviation)
Week 2 (n= 182)	-1.32 ( 2.10 )
Week 4 (n= 181)	-2.06 ( 2.16 )
Week 8 (n= 175)	-2.38 ( 2.40 )
Week 12 (n= 165)	-2.72 ( 2.28 )
Week 18 (n= 154)	-3.04 ( 2.57 )

No statistical analyses for this end point

Secondary: Double Blind Phase: Change From Double-Blind Baseline in Childhood Health Assessment Questionnaire (CHAQ)- Discomfort Index at Week 20, 24, 28, 32, 36,40 and 44

Top of page

End point title

Double Blind Phase: Change From Double-Blind Baseline in Childhood Health Assessment Questionnaire (CHAQ)- Discomfort Index at Week 20, 24, 28, 32, 36,40 and 44

End point description

CHAQ is a validated instrument and comprises of two indices, Disability and Discomfort, and global assessment of arthritis (overall well-being). Discomfort Index included: assessment of discomfort, the parent/legal guardian/subject were asked to provide a response to the question: How much pain do you think your child had because of his or her illness in the past week?, The parent/legal guardian/ participant rated the overall pain on a 0 to 10 VAS, where ‘0’ indicates ‘No Pain’ and ‘10’ indicates ‘Very Severe Pain’, higher scores indicates more severity.DBJAS: all subjects randomized to DB phase, received at least 1 dose of study medication in DB phase and had polyarticular course JIA. Here, “n” signifies subjects evaluable for this endpoint at specified time points.

End point type

Secondary

End point timeframe

Double Blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36,40 and 44

End point values	Tofacitinib: Double Blind Phase	Placebo
Number of subjects analysed	72	70
Units: Score on scale
arithmetic mean (standard deviation)
Week 20 (n= 71, 70)	0.08 ( 0.20 )	0.40 ( 0.20 )
Week 24 (n= 66, 60)	-0.01 ( 0.24 )	0.94 ( 0.24 )
Week 28 (n= 63, 49)	-0.23 ( 0.24 )	0.64 ( 0.25 )
Week 32 (n= 59, 45)	0.07 ( 0.27 )	1.06 ( 0.29 )
Week 36 (n= 55, 37)	-0.21 ( 0.21 )	0.32 ( 0.24 )
Week 40 (n= 53, 35)	-0.22 ( 0.24 )	0.49 ( 0.26 )
Week 44 (n= 49, 33)	-0.36 ( 0.23 )	0.44 ( 0.25 )

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 20: The analysis was based on a MMRM with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the Double-Blind baseline value

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1894

Method

MMRM

Parameter type

LS Mean Difference

Point estimate

-0.32

Confidence interval

level

95%

sides

2-sided

lower limit

-0.8

upper limit

0.16

Variability estimate

Standard error of the mean

Dispersion value

0.24

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 24: The analysis was based on a MMRM with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the Double-Blind baseline value

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0026

Method

MMRM

Parameter type

LS mean difference

Point estimate

-0.95

Confidence interval

level

95%

sides

2-sided

lower limit

-1.56

upper limit

-0.34

Variability estimate

Standard error of the mean

Dispersion value

0.31

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 28: The analysis was based on a MMRM with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the Double-Blind baseline value

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0067

Method

MMRM

Parameter type

LS mean difference

Point estimate

-0.87

Confidence interval

level

95%

sides

2-sided

lower limit

-1.5

upper limit

-0.25

Variability estimate

Standard error of the mean

Dispersion value

0.31

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 32: The analysis was based on a MMRM with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the Double-Blind baseline value

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0091

Method

MMRM

Parameter type

LS mean difference

Point estimate

-0.99

Confidence interval

level

95%

sides

2-sided

lower limit

-1.73

upper limit

-0.25

Variability estimate

Standard error of the mean

Dispersion value

0.37

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 36: The analysis was based on a MMRM with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the Double-Blind baseline value

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0632

Method

MMRM

Parameter type

LS mean difference

Point estimate

-0.53

Confidence interval

level

95%

sides

2-sided

lower limit

-1.09

upper limit

0.03

Variability estimate

Standard error of the mean

Dispersion value

0.28

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 40: The analysis was based on a MMRM with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the Double-Blind baseline value

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0306

Method

MMRM

Parameter type

LS mean difference

Point estimate

-0.71

Confidence interval

level

95%

sides

2-sided

lower limit

-1.35

upper limit

-0.07

Variability estimate

Standard error of the mean

Dispersion value

0.32

Tofacitinib: Double Blind Phase Vs Placebo

Statistical analysis description

Week 44: The analysis was based on a MMRM with fixed effects of treatment, visit, JIA category, open-label baseline CRP, treatment-by-visit interaction, and the Double-Blind baseline value

Comparison groups

Tofacitinib: Double Blind Phase v Placebo

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0118

Method

MMRM

Parameter type

LS mean difference

Point estimate

-0.8

Confidence interval

level

95%

sides

2-sided

lower limit

-1.41

upper limit

-0.18

Variability estimate

Standard error of the mean

Dispersion value

0.31

Secondary: Open-Label Phase: Percentage of Subjects With Active Uveitis at Baseline

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End point title

Open-Label Phase: Percentage of Subjects With Active Uveitis at Baseline

End point description

Uveitis is the inflammation of the uvea. Subjects were assessed for presence of uveitis (according to Standard Uveitis Nomenclature [SUN]). If Uveitis was present in participant at Baseline, it was considered as "active uveitis"; If Uveitis was not present in subject at Baseline, it was considered as "Inactive uveitis". As per SUN, Uveitis is defined as: anterior (in which anterior chamber is primary site of inflammation); intermediate (primary site of inflammation: vitreous); posterior (primary site of inflammation: retina or choroid). Percentage of participants with active uveitis (of any type) are reported. OLFAS: all subjects who were enrolled into OL phase of the study and received at least one dose of study medication in OL phase.

End point type

Secondary

End point timeframe

Baseline

End point values	Tofacitinib: Open-Label Phase
Number of subjects analysed	225
Units: percentage of subjects
number (not applicable)
Present	0.0

No statistical analyses for this end point

Secondary: Double Blind Phase: Percentage of Subjects With Active Uveitis at Week 24 and Week 44

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End point title

Double Blind Phase: Percentage of Subjects With Active Uveitis at Week 24 and Week 44

End point description

Uveitis is the inflammation of the uvea. Subjects were assessed for presence of uveitis (according to Standard Uveitis Nomenclature [SUN]). If Uveitis was present in participant at Baseline, it was considered as "active uveitis"; If Uveitis was not present in subject at Baseline, it was considered as "Inactive uveitis". As per SUN, Uveitis is defined as: anterior (in which anterior chamber is primary site of inflammation); intermediate (primary site of inflammation: vitreous); posterior (primary site of inflammation: retina or choroid). Percentage of participants with active uveitis (of any type) are reported. The double-blind safety analysis set (DBSAS): all subjects who have received at least one dose of study medication in double-blind phase.

End point type

Secondary

End point timeframe

Weeks 24 and 44

End point values	Tofacitinib: Double Blind Phase	Placebo
Number of subjects analysed	88	85
Units: percentage of subjects
number (not applicable)
Week 24: Present	0.0	1.2
Week 44: Present	0.0	0.0

No statistical analyses for this end point

Secondary: Open-Label Phase: Change from Baseline in the Tender Entheseal Assessment at Week 2, 4, 8, 12 and 18

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End point title

Open-Label Phase: Change from Baseline in the Tender Entheseal Assessment at Week 2, 4, 8, 12 and 18

End point description

Subjects with enthesitis-related arthritis (ERA) undergo Tender entheseal assessment. Tender entheseal assessment: Entheses were assessed and coded as: 1= any tenderness, 0= no tenderness, NE= not evaluable. Total number of tender entheses: 66*(total number of tender entheses with counts > 0)/number of non-missing tender entheses. If > 33 tender entheseal counts were missing, total number of tender entheses was defined as missing. OLERA: all subjects who were enrolled into OL phase of study and received at least 1 dose of study medication in the OL phase with ERA. Here, “n” signifies subjects evaluable for this endpoint at specified time points.

End point type

Secondary

End point timeframe

Baseline, Weeks 2, 4, 8, 12 and 18

End point values	Tofacitinib: Open-Label Phase
Number of subjects analysed	21
Units: Tender entheses
arithmetic mean (standard deviation)
Week 2 (n=21)	-1.57 ( 3.61 )
Week 4 (n=21)	-2.52 ( 3.92 )
Week 8 (n=20)	-3.05 ( 4.45 )
Week 12 (n=20)	-3.15 ( 4.93 )
Week 18 (n=20)	-3.50 ( 4.70 )

No statistical analyses for this end point

Secondary: Double Blind Phase: Change from Double-Blind Baseline in the Tender Entheseal Assessment at Week 20, 24, 28, 32, 36, 40 and 44

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End point title

Double Blind Phase: Change from Double-Blind Baseline in the Tender Entheseal Assessment at Week 20, 24, 28, 32, 36, 40 and 44

End point description

Subjects with enthesitis-related arthritis (ERA) undergo Tender entheseal assessment. Tender entheseal assessment: Entheses were assessed and coded as: 1= any tenderness, 0= no tenderness, NE= not evaluable. Total number of tender entheses: 66*(total number of tender entheses with counts > 0)/number of non-missing tender entheses. If > 33 tender entheseal counts were missing, total number of tender entheses was defined as missing. DBERA: all subjects randomized to the DB phase who received at least 1 dose of study medication in the DB phase with ERA. Here, “n” signifies subjects evaluable for this endpoint at specified time points.

End point type

Secondary

End point timeframe

Double Blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36, 40 and 44

End point values	Tofacitinib: Double Blind Phase	Placebo
Number of subjects analysed	9	7
Units: Tender entheses
arithmetic mean (standard deviation)
Week 20 (n= 9, 7)	0.00 ( 0.87 )	0.86 ( 2.61 )
Week 24 (n= 9, 5)	-1.00 ( 3.46 )	0.40 ( 2.19 )
Week 28 (n= 7, 4)	-0.43 ( 2.57 )	-0.75 ( 0.96 )
Week 32 (n= 6, 4)	0.33 ( 1.97 )	0.00 ( 0.82 )
Week 36 (n= 6, 3)	-0.83 ( 2.04 )	0.33 ( 0.58 )
Week 40 (n= 5, 3)	-2.00 ( 4.47 )	0.33 ( 0.58 )
Week 44 (n= 5, 3)	-2.00 ( 5.66 )	-0.33 ( 0.58 )

No statistical analyses for this end point

Secondary: Open-Label Phase: Change from Baseline in the Modified Schober’s Test at Week 2, 4, 8, 12 and 18

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End point title

Open-Label Phase: Change from Baseline in the Modified Schober’s Test at Week 2, 4, 8, 12 and 18

End point description

Subjects with ERA undergo Modified Schober’s Test. Modified Schober’s Test: a) Measurement 10 cm above and 5 cm below the lumbosacral junction (the dimples of Venus) in the upright position. b) Measurement of the distance between the upper and the lower marks when the child is bending forward. OLERA: all subjects who were enrolled into OL phase of study and received at least 1 dose of study medication in the OL phase with ERA. Here, “n” signifies subjects evaluable for this endpoint at specified time points.

End point type

Secondary

End point timeframe

Baseline, Weeks 2, 4, 8, 12 and 18

End point values	Tofacitinib: Open-Label Phase
Number of subjects analysed	21
Units: Centimeter (cm)
arithmetic mean (standard deviation)
Week 2 (n= 16)	-0.35 ( 1.02 )
Week 4 (n= 15)	-0.20 ( 1.03 )
Week 8 (n= 16)	-0.12 ( 1.15 )
Week 12 (n= 16)	0.02 ( 1.05 )
Week 18 (n= 16)	0.29 ( 1.08 )

No statistical analyses for this end point

Secondary: Double Blind Phase: Change from Baseline in the Modified Schober’s Test at Week 20, 24, 28, 32, 36, 40 and 44

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End point title

Double Blind Phase: Change from Baseline in the Modified Schober’s Test at Week 20, 24, 28, 32, 36, 40 and 44

End point description

Subjects with ERA undergo Modified Schober’s Test. Modified Schober’s Test: a) Measurement 10 cm above and 5 cm below the lumbosacral junction (the dimples of Venus) in the upright position. b) Measurement of the distance between the upper and the lower marks when the child is bending forward. DBERA: all subjects randomized to the DB phase who received at least 1 dose of study medication in the DB phase with ERA. Here, “n” signifies subjects evaluable for this endpoint at specified time points.

End point type

Secondary

End point timeframe

Double Blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36, 40 and 44

End point values	Tofacitinib: Double Blind Phase	Placebo
Number of subjects analysed	9	7
Units: cm
arithmetic mean (standard deviation)
Week 20 (n= 7, 5)	-0.46 ( 1.61 )	-0.28 ( 0.47 )
Week 24 (n= 7, 4)	-0.44 ( 1.27 )	-0.35 ( 0.54 )
Week 28 (n= 5, 3)	0.32 ( 1.38 )	-0.17 ( 0.57 )
Week 32 (n= 4, 3)	0.42 ( 1.84 )	0.63 ( 1.26 )
Week 36 (n= 3, 2)	-0.53 ( 0.84 )	0.05 ( 0.21 )
Week 40 (n= 3, 2)	0.57 ( 1.62 )	0.85 ( 0.64 )
Week 44 (n= 3, 2)	0.50 ( 0.87 )	1.05 ( 2.47 )

No statistical analyses for this end point

Secondary: Open-Label Phase: Change from Baseline in the Overall Back Pain and Nocturnal Back Pain responses at Week 2, 4, 8, 12 and 18

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End point title

Open-Label Phase: Change from Baseline in the Overall Back Pain and Nocturnal Back Pain responses at Week 2, 4, 8, 12 and 18

End point description

Subjects with ERA undergo Overall Back Pain and Nocturnal Back Pain assessment. For Overall Back Pain, parent/legal guardian/subject were asked to provide a response to the question: What is the amount of back pain at any time that your child experienced in the past week? And For Nocturnal Back Pain: What is the amount of back pain at night that your child experienced in the past week?. Response to these questions was provided by parent/legal guardian/ subject using a VAS of 0-10, where 0= No Pain and 10= Most Severe Pain, higher score indicated more severe pain. OLERA: all subjects who were enrolled into OL phase of study and received at least 1 dose of study medication in the OL phase with ERA. Here, “n” signifies subjects evaluable for this endpoint at specified time points.

End point type

Secondary

End point timeframe

Baseline, Weeks 2, 4, 8, 12 and 18

End point values	Tofacitinib: Open-Label Phase
Number of subjects analysed	21
Units: Score on scale
arithmetic mean (standard deviation)
Week 2: Nocturnal Back Pain (n=21)	-1.21 ( 3.10 )
Week 4:Nocturnal Back Pain (n=21)	-1.33 ( 3.44 )
Week 8:Nocturnal Back Pain (n=20)	-1.80 ( 3.18 )
Week 12: Nocturnal Back Pain (n=20)	-2.30 ( 2.63 )
Week 18: Back Pain at Night (n=20)	-1.98 ( 2.94 )
Week 2: Overall back pain (n=21)	-1.81 ( 2.89 )
Week 4: Overall back pain (n=21)	-1.86 ( 3.29 )
Week 8:Overall back pain (n=20)	-2.65 ( 2.72 )
Week 12:Overall back pain (n=20)	-3.20 ( 2.54 )
Week 18:Overall back pain (n=20)	-3.30 ( 2.45 )

No statistical analyses for this end point

Secondary: Double Blind Phase: Change from Double-Blind Baseline in the Overall Back Pain and Nocturnal Back Pain responses at Week 20, 24, 28, 32, 36, 40 and 44

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End point title

Double Blind Phase: Change from Double-Blind Baseline in the Overall Back Pain and Nocturnal Back Pain responses at Week 20, 24, 28, 32, 36, 40 and 44

End point description

Subjects with ERA undergo Overall Back Pain and Nocturnal Back Pain assessment. For Overall Back Pain, parent/legal guardian/subject were asked to provide a response to the question: What is the amount of back pain at any time that your child experienced in the past week? And For Nocturnal Back Pain: What is the amount of back pain at night that your child experienced in the past week?. Response to these questions was provided by parent/legal guardian/ subject using a VAS of 0-10, where 0= No Pain and 10= Most Severe Pain, higher score indicated more severe pain. DBERA: all subjects randomized to the DB phase who received at least 1 dose of study medication in the DB phase with ERA. Here, “n” signifies subjects evaluable for this endpoint at specified time points.

End point type

Secondary

End point timeframe

Double Blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36, 40 and 44

End point values	Tofacitinib: Double Blind Phase	Placebo
Number of subjects analysed	9	7
Units: Score on scale
arithmetic mean (standard deviation)
Week 20: Nocturnal Back Pain (n= 9, 7)	-0.17 ( 0.87 )	0.57 ( 0.93 )
Week 24: Nocturnal Back Pain (n= 9, 5)	-1.06 ( 1.96 )	0.10 ( 0.42 )
Week 28: Nocturnal Back Pain(n= 7, 4)	-0.79 ( 2.00 )	0.00 ( 0.41 )
Week 32: Nocturnal Back Pain (n= 6,4)	-1.58 ( 1.63 )	0.38 ( 0.63 )
Week 36: Nocturnal Back Pain (n= 6,3)	-0.75 ( 2.27 )	0.17 ( 0.29 )
Week 40: Nocturnal Back Pain (n= 5, 3)	-2.00 ( 2.26 )	0.17 ( 0.29 )
Week 44: Nocturnal Back Pain(n= 5, 3)	-0.80 ( 2.20 )	0.17 ( 0.29 )
Week 20: Overall back pain (n= 9, 7)	0.28 ( 1.89 )	0.57 ( 1.40 )
Week 24: Overall back pain (n= 9, 5)	0.39 ( 2.10 )	0.00 ( 0.79 )
Week 28:Overall back pain (n= 7, 4)	0.00 ( 2.60 )	-0.25 ( 0.29 )
Week 32: Overall back pain (n= 6, 4)	-1.75 ( 2.25 )	-0.13 ( 0.48 )
Week 36: Overall back pain (n= 6, 3)	0.17 ( 1.29 )	-0.50 ( 0.87 )
Week 40: Overall back pain (n= 5, 3)	0.30 ( 1.79 )	-0.50 ( 0.87 )
Week 44: Overall back pain (n= 5, 3)	-0.10 ( 3.45 )	-0.50 ( 0.87 )

No statistical analyses for this end point

Secondary: Open-Label Phase: Changes From Baseline in Percentage of Body Surface Area (BSA) Affected with Psoriasis at Weeks 2, 4, 8, 12 and 18

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End point title

Open-Label Phase: Changes From Baseline in Percentage of Body Surface Area (BSA) Affected with Psoriasis at Weeks 2, 4, 8, 12 and 18

End point description

Percentage of body surface area affected by psoriasis was estimated using the palm method: one of the participant’s palm to proximal interphalangeal (PIP) and thumb = 1% of BSA. Regions of the body were assigned specific number of palms with percentage (Head and Neck = 10% [10 palms], Upper extremities = 20% [20 palms], Trunk [axillae and groin] = 30% [30 palms], Lower extremities [buttocks] = 40% [40 palms]) The total BSA affected was the summation of individual regions affected. OLPsA: all subjects who were enrolled into the OL phase of study and received at least 1 dose of study medication in OL phase with PsA. Here, “n” signifies subjects evaluable for this endpoint at specified time points.

End point type

Secondary

End point timeframe

Baseline, Weeks 2, 4, 8, 12 and 18

End point values	Tofacitinib: Open-Label Phase
Number of subjects analysed	20
Units: Percentage of BSA
arithmetic mean (standard deviation)
Week 2 (n=20)	0.55 ( 4.70 )
Week 4 (n=19)	-1.03 ( 2.49 )
Week 8 (n=17)	-0.29 ( 6.11 )
Week 12 (n=18)	-0.36 ( 5.93 )
Week 18 (n=16)	-0.46 ( 6.48 )

No statistical analyses for this end point

Secondary: Double Blind Phase: Changes From Double Blind Baseline in Percentage of Body Surface Area (BSA) Affected with Psoriasis at Week 20, 24, 28, 32, 36, 40 and 44

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End point title

Double Blind Phase: Changes From Double Blind Baseline in Percentage of Body Surface Area (BSA) Affected with Psoriasis at Week 20, 24, 28, 32, 36, 40 and 44

End point description

Percentage of body surface area affected by psoriasis was estimated using the palm method: one of the participant’s palm to PIP and thumb = 1% of BSA. Regions of the body were assigned specific number of palms with percentage (Head and Neck = 10% [10 palms], Upper extremities = 20% [20 palms], Trunk [axillae and groin] = 30% [30 palms], Lower extremities [buttocks] = 40% [40 palms]) The total BSA affected was the summation of individual regions affected. DBPsA: all subjects randomized to the DB phase who received at least 1 dose of study medication in the DB phase with PsA. Here, “n” signifies subjects evaluable for this endpoint at specified time points.

End point type

Secondary

End point timeframe

Double Blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36, 40 and 44

End point values	Tofacitinib: Double Blind Phase	Placebo
Number of subjects analysed	7	8
Units: Percentage of BSA
arithmetic mean (standard deviation)
Week 20 (n= 6, 8)	-0.50 ( 1.22 )	0.28 ( 0.70 )
Week 24 (n= 7, 8)	-0.14 ( 0.38 )	0.85 ( 1.71 )
Week 28 (n= 5, 3)	-4.20 ( 8.84 )	0.33 ( 0.58 )
Week 32 (n= 5, 3)	-0.60 ( 1.34 )	1.67 ( 2.89 )
Week 36 (n= 5, 3)	-4.20 ( 8.90 )	1.33 ( 2.31 )
Week 40 (n= 5, 3)	-4.60 ( 8.71 )	0.67 ( 1.15 )
Week 44 (n= 5, 2)	-4.60 ( 8.71 )	-0.05 ( 0.07 )

No statistical analyses for this end point

Secondary: Open-Label Phase: Changes From Baseline in Physician's Global Assessment (PGA) of Psoriasis Assessments at Week 2, 4, 8, 12 and 18

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End point title

Open-Label Phase: Changes From Baseline in Physician's Global Assessment (PGA) of Psoriasis Assessments at Week 2, 4, 8, 12 and 18

End point description

PsA assessed PGA of psoriasis. The PGA of psoriasis was scored on a 6-point scale, reflecting a global consideration of the erythema, induration, and scaling across all psoriatic lesions. Average erythema, induration, and scaling are scored separately over the whole body according to a 5-point severity scale (0 [no symptom] to 5 [severe symptom]). The total score was calculated as average of the 3 severity scores and rounded to the nearest whole number score to determine the PGA score and ranged as 0= no evidence to 5=sever, higher score indicates more severity. OLPsA: all subjects who were enrolled into the OL phase of study and received at least 1 dose of study medication in OL phase with PsA. Here, “n” signifies subjects evaluable for this end point at specified time points.

End point type

Secondary

End point timeframe

Baseline, Weeks 2, 4, 8, 12 and 18

End point values	Tofacitinib: Open-Label Phase
Number of subjects analysed	20
Units: Score on scale
arithmetic mean (standard deviation)
Week 2 (n= 20)	-0.05 ( 0.39 )
Week 4 (n= 19)	-0.42 ( 0.84 )
Week 8 (n= 17)	-0.29 ( 0.92 )
Week 12 (n= 18)	-0.56 ( 0.86 )
Week 18 (n= 16)	-0.56 ( 1.03 )

No statistical analyses for this end point

Secondary: Double Blind Phase: Changes From Double-Blind Baseline in Physician's Global Assessment (PGA) of Psoriasis Assessments at Week 20, 24, 28, 32, 36, 40 and 44

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End point title

Double Blind Phase: Changes From Double-Blind Baseline in Physician's Global Assessment (PGA) of Psoriasis Assessments at Week 20, 24, 28, 32, 36, 40 and 44

End point description

PsA assessed PGA of psoriasis. The PGA of psoriasis was scored on a 6-point scale, reflecting a global consideration of the erythema, induration, and scaling across all psoriatic lesions. Average erythema, induration, and scaling are scored separately over the whole body according to a 5-point severity scale (0 [no symptom] to 5 [severe symptom]). The total score was calculated as average of the 3 severity scores and rounded to the nearest whole number score to determine the PGA score and ranged as 0= no evidence to 5=sever, higher score indicates more severity. DBPsA: all subjects randomized to the DB phase who received at least 1 dose of study medication in the DB phase with PsA. Here, “n” signifies subjects evaluable for this end point at specified time points.

End point type

Secondary

End point timeframe

Double blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36, 40 and 44

End point values	Tofacitinib: Double Blind Phase	Placebo
Number of subjects analysed	7	8
Units: Score on scale
arithmetic mean (standard deviation)
Week 20 (n= 7, 8)	0.14 ( 0.38 )	0.00 ( 0.00 )
Week 24 (n= 7, 8)	0.14 ( 0.38 )	0.38 ( 0.52 )
Week 28 (n= 5, 3)	0.20 ( 0.45 )	0.33 ( 0.58 )
Week 32 (n= 5, 3)	0.00 ( 0.00 )	0.33 ( 0.58 )
Week 36 (n= 5, 3)	0.00 ( 0.00 )	0.33 ( 0.58 )
Week 40 (n= 5, 3)	0.00 ( 0.00 )	0.00 ( 0.00 )
Week 44 (n= 5, 2)	0.00 ( 0.00 )	-0.50 ( 0.71 )

No statistical analyses for this end point

Secondary: Open-Label Phase: Taste Assessment of Tofacitinib Oral Solution on Day 14

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End point title

Open-Label Phase: Taste Assessment of Tofacitinib Oral Solution on Day 14

End point description

Oral solution was used in subjects weighing less than (<) 40 kilogram (kg) and in subjects who are unable to swallow tablets. Taste acceptability was assessed by asking the subjects to select one of several choices which reflects the subject’s response to taste. Taste acceptability assessment response included: dislike Very Much, dislike a Little, Not Sure, like a little and like Very Much. OLFAS: all subjects who were enrolled into OL phase and received at least 1 dose of study medication in OL phase . Here, Number of subjects analysed signifies subjects who were evaluable for this end point.

End point type

Secondary

End point timeframe

Day 14

End point values	Tofacitinib: Open-Label Phase
Number of subjects analysed	84
Units: subjects
Dislike Very Much	4
Dislike a Little	8
Not Sure	6
Like a Little	32
Like Very Much	34

No statistical analyses for this end point

Secondary: Open-Label Phase: Number of Subjects With Serious Infections, Cytopenia, Malignancies and Cardiovascular Diseases

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End point title

Open-Label Phase: Number of Subjects With Serious Infections, Cytopenia, Malignancies and Cardiovascular Diseases

End point description

Serious infection defined as any infection that requires hospitalization for treatment or requires parenteral antimicrobial therapy or meets other criteria that require it to be classified as a serious adverse event. Cytopenia was categorized as: lymphocyte counts: <500 lymphocytes/ millimeter^3 (mm), neutrophil counts <1000 neutrophils/mm^3, platelet counts <100,000 platelets/mm^3, any single hemoglobin value <8 grams/decilitre (g/dL) and any single hemoglobin value drops >=2 g/dL below baseline. Number of Subjects with serious infections, cytopenia, malignancies and Cardiovascular Diseases are reported. OLFAS: all subjects who were enrolled into OL phase and received at least 1 dose of study medication in OL phase

End point type

Secondary

End point timeframe

From the first dose of study drug up to week 18

End point values	Tofacitinib: Open-Label Phase
Number of subjects analysed	225
Units: subjects
Serious Infections	3
Cytopenia: Lymphocyte counts <500 lymphocytes/mm^3	1
Cytopenia:Neutrophil counts <1000 neutrophils/mm^3	4
Cytopenia:Platelet counts <100,000 platelets/mm^3	1
Cytopenia:Any single hemoglobin value <8 g/dL	1
Cytopenia:Any hg value drops>=2g/dL below baseline	17
Malignancies	0
Cardiovascular Diseases	0

No statistical analyses for this end point

Secondary: Double Blind Phase: Number of Subjects With Serious Infections, Cytopenia, Malignancies and Cardiovascular Diseases

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End point title

Double Blind Phase: Number of Subjects With Serious Infections, Cytopenia, Malignancies and Cardiovascular Diseases

End point description

Serious infection defined as any infection that requires hospitalization for treatment or requires parenteral antimicrobial therapy or meets other criteria that require it to be classified as a serious adverse event. Cytopenia was categorized as: lymphocyte counts: <500 lymphocytes/ millimeter^3 (mm), neutrophil counts <1000 neutrophils/mm^3, platelet counts <100,000 platelets/mm^3, any single hemoglobin value <8 grams/decilitre (g/dL) and any single hemoglobin value drops >=2 g/dL below baseline. Number of Subjects with serious infections, cytopenia, malignancies and Cardiovascular Diseases are reported. DBFAS: all subjects randomized to DB phase who received at least 1 dose of study medication in DB phase.

End point type

Secondary

End point timeframe

Screening up to week 44

End point values	Tofacitinib: Double Blind Phase	Placebo
Number of subjects analysed	88	85
Units: subjects
Serious Infections	0	1
Cytopenia: Lymphocyte counts <500 lymphocytes/mm^3	0	0
Cytopenia:Neutrophil counts <1000 neutrophils/mm^3	0	2
Cytopenia:Platelet counts <100,000 platelets/mm^3	1	0
Cytopenia:Any single hemoglobin value <8 g/dL	0	0
Cytopenia:Any hg value drops>=2g/dL below baseline	3	7
Malignancies	0	0
Cardiovascular Diseases	0	0

No statistical analyses for this end point

Secondary: Open-Label Phase: Number of Subjects With Tanner Staging Evaluation (Pubic Hair)

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End point title

Open-Label Phase: Number of Subjects With Tanner Staging Evaluation (Pubic Hair)

End point description

Tanner stage is a scale used to document the stage of development of puberty by assessing the secondary sexual characteristics: Pubic hair (both male and female), breast size (for females); and size of the genitalia (for males).were assessed in this study and with values in the scale ranging from: Stage 1: no hair, Stage 2: downy hair, Stage 3: Scant terminal hair, Stage 4: Terminal hair that fills the entire triangle overlying the pubic region and Stage 5: Terminal hair that extends beyond the inguinal crease onto the thigh. Tanner Stage for pubic hair at Day 1 was summarized and reported using number of subjects in each stage. OLFAS: all subjects who were enrolled into OL phase and received at least 1 dose of study medication in OL phase. Here, Number of subjects analyzed signifies subjects who were evaluable for this end point.

End point type

Secondary

End point timeframe

Day 1

End point values	Tofacitinib: Open-Label Phase
Number of subjects analysed	218
Units: subjects
Stage 1	73
Stage 2	21
Stage 3	25
Stage 4	47
Stage 5	52

No statistical analyses for this end point

Secondary: Double Blind Phase: Number of Subjects With Tanner Staging Evaluation (Pubic Hair)

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End point title

Double Blind Phase: Number of Subjects With Tanner Staging Evaluation (Pubic Hair)

End point description

Tanner stage is a scale used to document the stage of development of puberty by assessing the secondary sexual characteristics: Pubic hair (both male and female), breast size (for females); and size of the genitalia (for males).were assessed in this study and with values in the scale ranging from: Stage 1: no hair, Stage 2: downy hair, Stage 3: Scant terminal hair, Stage 4: Terminal hair that fills the entire triangle overlying the pubic region and Stage 5: Terminal hair that extends beyond the inguinal crease onto the thigh. Tanner Stage for pubic hair at Week 44 was summarized and reported using number of subjects in each stage. DB safety analysis set (DBSAS): all subjects who have received atleast 1 dose of study medication in DB phase. Here, Number of subjects analyzed signifies subjects who were evaluable for this end point.

End point type

Secondary

End point timeframe

Week 44

End point values	Tofacitinib: Double Blind Phase	Placebo
Number of subjects analysed	56	38
Units: subjects
Stage 1	13	7
Stage 2	8	7
Stage 3	8	3
Stage 4	14	4
Stage 5	13	17

No statistical analyses for this end point

Secondary: Open-Label Phase: Number of Subjects With Tanner Staging Evaluation (Breast Exam)

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End point title

Open-Label Phase: Number of Subjects With Tanner Staging Evaluation (Breast Exam)

End point description

Tanner stage is a scale used to document the stage of development of puberty by assessing the secondary sexual characteristics: Pubic hair (both male and female), breast size (for females); and size of the genitalia (for males).were assessed in this study and with values in the scale ranging from: Stage 1: No glandular breast tissue palpable, Stage 2: Breast bud palpable under areola (1st pubertal sign in females), Stage 3: Breast tissue palpable outside areola; no areolar development, Stage 4: Areola elevated above contour of the breast, forming “double scoop” appearance, Stage 5: Areolar mound recedes back into single breast contour with areolar hyperpigmentation, papillae development and nipple protrusion. OLFAS: all subjects who were enrolled into OL phase and received at least 1 dose of study medication in OL phase. Here, Number of subjects analyzed signifies subjects who were evaluable for this end point.

End point type

Secondary

End point timeframe

Day 1

End point values	Tofacitinib: Open-Label Phase
Number of subjects analysed	163
Units: subjects
Stage 1	42
Stage 2	19
Stage 3	28
Stage 4	34
Stage 5	40

No statistical analyses for this end point

Secondary: Double Blind Phase: Number of Subjects With Tanner Staging Evaluation (Breast Exam)

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End point title

Double Blind Phase: Number of Subjects With Tanner Staging Evaluation (Breast Exam)

End point description

Tanner stage is a scale used to document the stage of development of puberty by assessing the secondary sexual characteristics: Pubic hair (both male and female), breast size (for females); and size of the genitalia (for males).were assessed in this study and with values in the scale ranging from: Stage 1: No glandular breast tissue palpable, Stage 2: Breast bud palpable under areola (1st pubertal sign in females), Stage 3: Breast tissue palpable outside areola; no areolar development, Stage 4: Areola elevated above contour of the breast, forming “double scoop” appearance, Stage 5: Areolar mound recedes back into single breast contour with areolar hyperpigmentation, papillae development and nipple protrusion. DBSAS: all subjects who have received at least 1 dose of study medication in DB phase. Here, Number of subjects analyzed signifies subjects who were evaluable for this end point.

End point type

Secondary

End point timeframe

Week 44

End point values	Tofacitinib: Double Blind Phase	Placebo
Number of subjects analysed	43	28
Units: subjects
Stage 1	6	8
Stage 2	8	2
Stage 3	7	2
Stage 4	13	3
Stage 5	9	13

No statistical analyses for this end point

Secondary: Open-Label Phase: Number of Subjects With Tanner Staging Evaluation (Genitalia)

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End point title

Open-Label Phase: Number of Subjects With Tanner Staging Evaluation (Genitalia)

End point description

Tanner stage is a scale used to document the stage of development of puberty by assessing the secondary sexual characteristics: Pubic hair (both male and female), breast size (for females); and size of the genitalia (for males).were assessed in this study and with values in the scale ranging from: Stage 1: Testicular volume < 4 ml or long axis < 2.5 cm, Stage 2: 4 ml-8 ml (or 2.5-3.3 cm long), 1st pubertal sign in males, Stage 3: 9 ml-12 ml (or 3.4-4.0 cm long), Stage 4: 15-20 ml (or 4.1-4.5 cm long), Stage 5: > 20 ml (or > 4.5 cm long). Tanner Stage for genitalia at Day 1 was summarized and reported using number of subjects in each stage. OLFAS: all subjects who were enrolled into OL phase and received at least 1 dose of study medication in OL phase. Here, Number of subjects analyzed signifies subjects who were evaluable for this end point.

End point type

Secondary

End point timeframe

Day 1

End point values	Tofacitinib: Open-Label Phase
Number of subjects analysed	55
Units: subjects
Stage 1	24
Stage 2	6
Stage 3	8
Stage 4	11
Stage 5	6

No statistical analyses for this end point

Secondary: Double Blind Phase: Number of Subjects With Tanner Staging Evaluation (Genitalia)

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End point title

Double Blind Phase: Number of Subjects With Tanner Staging Evaluation (Genitalia)

End point description

Tanner stage is a scale used to document the stage of development of puberty by assessing the secondary sexual characteristics: Pubic hair (both male and female), breast size (for females); and size of the genitalia (for males).were assessed in this study and with values in the scale ranging from: Stage 1: Testicular volume < 4 ml or long axis < 2.5 cm, Stage 2: 4 ml-8 ml (or 2.5-3.3 cm long), 1st pubertal sign in males, Stage 3: 9 ml-12 ml (or 3.4-4.0 cm long), Stage 4: 15-20 ml (or 4.1-4.5 cm long), Stage 5: > 20 ml (or > 4.5 cm long). Tanner Stage for genitalia at Day 1 was summarized and reported using number of subjects in each stage. DBSAS: all subjects who have received at least 1 dose of study medication in DB phase. Here, Number of subjects analyzed signifies subjects who were evaluable for this end point.

End point type

Secondary

End point timeframe

Week 44

End point values	Tofacitinib: Double Blind Phase	Placebo
Number of subjects analysed	13	10
Units: subjects
Stage 1	5	0
Stage 2	0	5
Stage 3	2	0
Stage 4	5	1
Stage 5	1	4

No statistical analyses for this end point

Secondary: Open-Label Phase: Number of Subjects With Laboratory Abnormalities

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End point title

Open-Label Phase: Number of Subjects With Laboratory Abnormalities

End point description

Hematology: Hemoglobin(Hg),hematocrit erythrocytes(Ery); <0.8*lower limit of normal (LLN), Ery. Mean Corpuscular Volume; <0.9*LLN, >1.1*ULN (Upper LN), Platelets; <0.5*LLN, >1.75*ULN, Leukocytes (leu); <0.6*LLN, >1.5*ULN, Lymphocytes (Ly), Ly/leu, Neutrophils, Neutrophils/leu <0.8*LLN, Basophils/leu, Eosinophils, Eosinophils/leu, Monocytes, Monocytes/leu >1.2*ULN, Ery Sedimentation Rate >1.5*ULN. Chemistry: Bilirubin, Indirect Bilirubin >1.5*ULN, AST, ALT, Gamma Glutamyl Transferase, Alkaline Phosphatase >3.0*ULN, Albumin >1.2*ULN, Creatinine >1.3*ULN, HDL Cholesterol (Chol)<0.8*LLN, LDL Chol, LDL Chol Friedewald Est PEG >1.2*ULN, Triglycerides >1.3*ULN, Calcium <0.9*LLN, Bicarbonate <0.9*LLN, Glucose >1.5*ULN, Creatine Kinase >2.0*ULN, C Reactive Protein >1.1*ULN, Chol >1.3*ULN. OLFAS analysis population used for this endpoint. ‘n’=subjects evaluable for this endpoint at specified time points.Only those category in which at least 1 subject data reported.

End point type

Secondary

End point timeframe

From the first dose of study drug up to Week 18

End point values	Tofacitinib: Open-Label Phase
Number of subjects analysed	225
Units: subjects
Hemoglobin (<0.8* LLN) (n= 224)	1
Hematocrit (<0.8* LLN) (n= 224)	1
Erythrocytes (<0.8* LLN)(n= 224)	2
Ery. Mean Corpuscular Volume (<0.9*LLN) (n= 224)	3
Ery. Mean Corpuscular Volume (>1.1*ULN ) (n= 224)	4
Platelets (<0.5*LLN) (n= 224)	1
Platelets (>1.75*ULN) (n= 224)	2
Leukocytes (<0.6*LLN) (n= 224)	1
Leukocytes (>1.5*ULN) (n= 224)	2
Lymphocytes (<0.8*LLN)(n= 224)	7
Lymphocytes (>1.2*ULN) (n= 224)	2
Lymphocytes/Leu.(<0.8*LLN) (n= 224)	15
Lymphocytes/Leu.(>1.2*ULN) (n= 224)	20
Neutrophils (<0.8*LLN) (n= 224)	8
Neutrophils (>1.2*ULN) (n= 224)	18
Neutrophils/Leu. (<0.8*LLN) (n= 224)	19
Basophils/Leu.(>1.2*ULN) (n= 224)	37
Eosinophils (>1.2*ULN) (n= 224)	53
Eosinophils/Leu.(>1.2*ULN) (n= 224)	32
Monocytes (>1.2*ULN) (n= 224)	3
Monocytes/Leu. (>1.2*ULN) (n= 224)	38
Ery. Sedimentation Rate (>1.5*ULN)(n= 224)	65
Bilirubin (>1.5*ULN) (n= 225)	1
Indirect Bilirubin (>1.5*ULN) (n= 225)	1
AST (>3.0*ULN) (n= 225)	4
ALT(>3.0*ULN) (n= 225)	5
GGT (>3.0*ULN) (n= 225)	1
Alkaline Phosphatase (>3.0*ULN)(n= 225)	1
Albumin (>1.2*ULN) (n= 225)	1
Creatinine (>1.3*ULN) (n= 225)	1
HDL Cholesterol (<0.8*LLN) (n= 223)	2
LDL Cholesterol (>1.2*ULN) (n= 87)	4
LDL Chol Friedewald Est PEG (>1.2*ULN) (n= 222)	1
Triglycerides(>1.3*ULN) (n= 222)	27
Calcium (<0.9*LLN) (n= 225)	1
Bicarbonate (<0.9*LLN) (n= 225)	10
Glucose (>1.5*ULN) (n= 225)	2
Creatine Kinase (>2.0*ULN) (n= 224)	12
C Reactive Protein (>1.1*ULN) (n= 225)	122
Cholesterol (>1.3*ULN) (n= 223)	2
Specific Gravity >1.030 (n= 225)	32
URINE Glucose(>1.030) (n= 225)	1
Ketones (>=1) (n= 225)	11
URINE Protein (>=1)(n= 225)	9
URINE Hemoglobin (>=1) (n= 225)	48
Nitrite (>=1) (n= 225)	6
Leukocyte Esterase (>=1) (n= 225)	59
URINE Erythrocytes (>=1) (n= 113)	23
URINE Leukocytes (>=20) (n= 150)	16
Hyaline Casts (>=1) (n= 3)	1

No statistical analyses for this end point

Secondary: Double Blind Phase: Number of Subjects With Laboratory Abnormalities

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End point title

Double Blind Phase: Number of Subjects With Laboratory Abnormalities

End point description

Hematology: Hg,Hematocrit Ery; <0.8*LLN,Ery. Mean Corpuscular Volume; <0.9*LLN, >1.1*ULN, Platelets; <0.5*LLN, Leu ; <0.6*LLN, >1.5*ULN, Lymphocytes >1.2*ULN, Lymphocytes/ Leu, Neutrophils, Neutrophils/Leu>1.2*ULN and <0.8*LLN,Basophils, Basophils/Leu, Eosinophils, Eosinophils/Leukocytes, Monocytes, Monocytes/Leu >1.2*ULN, Prothrombin Time >1.1*ULN, Erythrocyte Sedimentation Rate >1.5*ULN. Chemistry: Bilirubin, Direct Bilirubin, Indirect Bilirubin >1.5*ULN, ALT, AST, GGT >3.0*ULN,HDL Chol <0.8*LLN,Triglycerides >1.3*ULN, Potassium >1.1x ULN, Calcium, <0.9*LLN, Glucose >1.5*ULN, Bicarbonate <0.9*LLN, Creatine Kinase >2.0*ULN, C Reactive Protein >1.1*ULN. Urinalysis: Specific Gravity >1.030, pH >8, urine Glucose, Ketones, Protein, Hg, Nitrite, Leukocyte Esterase >=1, Ery, Leukocytes >=20, Hyaline Casts >1. Only those category in which at least 1 subject data reported.DBSAS analysis population used for this endpoint. ‘n’=subjects evaluable for this endpoint at specified time points.

End point type

Secondary

End point timeframe

From the first dose of study drug in double blind up to Week 44

End point values	Tofacitinib: Double Blind Phase	Placebo
Number of subjects analysed	88	85
Units: subjects
Hg. (<0.8*LLN) (n= 87, 85)	1	3
Hematocrit (<0.8*LLN) (n= 87, 85)	0	2
Ery. (<0.8*LLN) (n= 87, 85)	0	2
Ery. Mean Corpuscular Volume(<0.9*LLN)(n= 87, 85)	2	1
Ery. Mean Corpuscular Volume (>1.1*ULN)(n= 87, 85)	1	2
Platelets(<0.5*LLN) (n= 88, 84)	1	0
Leu. (<0.6*LLN) (n= 87, 85)	0	1
Leu.(>1.5*ULN)(n= 87, 85)	1	0
Lymphocytes(<0.8*LLN) (n= 87, 85)	5	1
Lymphocytes(>1.2*ULN)(n= 87, 85)	1	0
Lymphocytes/Leu. (<0.8*LLN) (n= 87, 85)	9	5
Lymphocytes/Leu.(>1.2*ULN) (n= 87, 85)	5	7
Neutrophils(<0.8*LLN) (n= 87, 85)	1	3
Neutrophils(>1.2*ULN) (n= 87, 85)	7	5
Neutrophils/Leu.(<0.8*LLN)(n= 87, 85)	5	6
Basophils(>1.2*ULN) (n= 87, 85)	1	0
Basophils/Leu.(>1.2*ULN) (n= 87, 85)	14	15
Eosinophils(>1.2*ULN) (n= 87, 85)	27	18
Eosinophils/Leu.(>1.2*ULN) (n= 87, 85)	21	14
Monocytes(>1.2*ULN) (n= 87, 85)	2	2
Monocytes/Leu.(>1.2*ULN) (n= 87, 85)	18	19
Prothrombin Time (>1.1*ULN)(n= 3, 2)	0	1
Ery. Sedimentation Rate (>1.5*ULN) (n= 88, 85)	26	19
Bilirubin (>1.5*ULN) (n= 88, 85)	1	0
Direct Bilirubin (>1.5*ULN) (n= 88, 85)	1	0
Indirect Bilirubin (>1.5*ULN)(n= 88, 85)	1	0
Alanine Aminotransferase (>3.0*ULN)(n= 88, 85)	1	2
GGT(>3.0*ULN) (n= 88, 85)	1	0
HDL Cholesterol (<0.8*LLN) (n= 70, 61)	0	2
Triglycerides(>1.3*ULN) (n= 71, 61)	8	6
Potassium (>1.1*ULN) (n= 88, 85)	1	0
Calcium (<0.9*LLN ) (n= 88, 85)	1	1
Glucose (>1.5*ULN) (n= 88, 85)	1	0
Creatine Kinase(>2.0*ULN) (n= 88, 85)	2	2
C Reactive Protein(>1.1*ULN) (n= 88, 85)	44	47
Specific Gravity (>1.030)(n= 88, 85)	12	7
pH (>8) (n= 88, 85)	0	1
URINE Glucose (>=1) (n= 88, 85)	1	1
Ketones (>=1) (n= 88, 85)	7	10
URINE Protein (>=1) (n= 88, 85)	4	4
URINE Hemoglobin (>=1) (n= 88, 85)	25	11
Nitrite (>=1) (n= 88, 85)	3	6
Leu. Esterase (>=1) (n= 88, 85)	26	25
URINE Ery.(>=20) (n= 51, 41)	10	6
URINE Leu. (>=20) (n= 66, 57)	6	6
Hyaline Casts (>1)(n= 2, 1)	1	1
Granular Casts (>1)(n=0,1)	0	1
Bicarbonate(<0.9*LLN) (n=88,85)	0	2

No statistical analyses for this end point

Secondary: Open-Label Phase: Number of Subjects With Physical Examination Abnormalities

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End point title

Open-Label Phase: Number of Subjects With Physical Examination Abnormalities

End point description

Physical examination included: abdomen, ears, extremities, eyes, general appearance, head, heart, lungs, lymph nodes, neurological, nose, skin, and throat. Abnormality in physical examination was based on investigator's discretion. OLFAS: all subjects who were enrolled into OL phase and received at least 1 dose of study medication in OL phase. ‘n’=subjects evaluable for this endpoint at specified time points.

End point type

Secondary

End point timeframe

Baseline, Weeks 2, 4, 8, 12 and 18

End point values	Tofacitinib: Open-Label Phase
Number of subjects analysed	225
Units: subjects
Abdomen: Baseline	1
Abdomen: Week 2	2
Abdomen: Week 4	3
Abdomen: Week 8	2
Abdomen: Week 12	2
Abdomen: Week 18	1
Ears: Baseline	5
Ears: Week 2	0
Ears: Week 4	0
Ears: Week 8	0
Ears: Week 12	0
Ears: Week 18	3
Extremities: Baseline	49
Extremities: Week 2	43
Extremities: Week 4	35
Extremities: Week 8	30
Extremities: Week 12	28
Extremities: Week 18	23
Eyes: Baseline	2
Eyes: Week 2	0
Eyes: Week 4	0
Eyes: Week 8	0
Eyes: Week 12	0
Eyes: Week 18	2
General appearance: Baseline	16
General appearance: Week 2	0
General appearance: Week 4	1
General appearance: Week 8	2
General appearance: Week 12	0
General appearance: Week 18	5
Head: Baseline	3
Head: Week 2	0
Head: Week 4	0
Head: Week 8	0
Head: Week 12	0
Head: Week 18	4
Heart: Baseline	0
Heart: Week 2	0
Heart: Week 4	0
Heart: Week 8	2
Heart: Week 12	0
Heart: Week 18	0
Lungs: Baseline	1
Lungs: Week 2	1
Lungs: Week 4	0
Lungs: Week 8	1
Lungs: Week 12	1
Lungs: Week 18	0
Lymph nodes: Baseline	2
Lymph nodes: Week 2	5
Lymph nodes: Week 4	5
Lymph nodes: Week 8	5
Lymph nodes: Week 12	3
Lymph nodes: Week 18	4
Neurological: Baseline	4
Neurological: Week 2	1
Neurological: Week 4	0
Neurological: Week 8	0
Neurological: Week 12	0
Neurological: Week 18	4
Nose: Baseline	0
Nose: Week 2	0
Nose: Week 4	0
Nose: Week 8	0
Nose: Week 12	0
Nose: Week 18	5
Skin: Baseline	27
Skin: Week 2	0
Skin: Week 4	1
Skin: Week 8	1
Skin: Week 12	0
Skin: Week 18	12
Throat: Baseline	1
Throat: Week 2	0
Throat: Week 4	0
Throat: Week 8	0
Throat: Week 12	0
Throat: Week 18	6

No statistical analyses for this end point

Secondary: Double Blind Phase: Number of Subjects With Physical Examination Abnormalities

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End point title

Double Blind Phase: Number of Subjects With Physical Examination Abnormalities

End point description

Physical examination included: abdomen, ears, extremities, eyes, general appearance, head, heart, lungs, lymph nodes, neurological, nose, skin, and throat. Abnormality in physical examination was based on investigator's discretion. DBSAS: all subjects who have received atleast 1 dose of study medication in DB phase. Here, ‘n’=subjects evaluable for this endpoint at specified time points.

End point type

Secondary

End point timeframe

Weeks 18, 20, 24, 28, 32, 36, 40 and 44

End point values	Tofacitinib: Double Blind Phase	Placebo
Number of subjects analysed	88	85
Units: subjects
Abdomen: Week 18 (n= 88, 84)	0	1
Abdomen: Week 20 (n= 87, 85)	1	1
Abdomen: Week 24 (n= 82, 73)	1	1
Abdomen: Week 28 (n= 75, 57)	0	0
Abdomen: Week 32 (n= 70, 52)	0	0
Abdomen: Week 36 (n= 66, 43)	0	0
Abdomen: Week 40 (n= 63, 41)	0	0
Abdomen: Week 44 (n= 59, 38)	0	0
Ears: Week 18 (n= 88, 84)	3	0
Ears: Week 20 (n= 4, 5)	0	0
Ears: Week 24 (n= 5, 5)	0	0
Ears: Week 28 (n= 2, 2)	0	0
Ears: Week 32 (n= 2, 3)	0	0
Ears: Week 40 (n= 1, 1)	0	1
Ears: Week 44 (n= 59, 38)	0	0
Extremities: Week 18 (n= 88, 84)	9	12
Extremities: Week 20 (n= 87, 85)	11	14
Extremities: Week 24 (n= 82, 73)	5	7
Extremities: Week 28 (n= 75, 57)	6	6
Extremities: Week 32 (n= 70, 52)	1	8
Extremities: Week 36 (n= 66, 43)	2	6
Extremities: Week 40 (n= 63, 41)	3	6
Extremities: Week 44 (n= 59, 38)	3	7
Eyes: Week 18 (n= 88, 84)	2	0
Eyes: Week 20 (n= 4, 5)	0	0
Eyes: Week 24 (n= 5, 5)	0	0
Eyes: Week 28 (n= 2, 2)	0	0
Eyes: Week 32 (n= 2, 3)	0	0
Eyes: Week 40 (n= 1,1)	0	0
Eyes: Week 44 (n= 59, 38)	1	0
General appearance: Week 18 (n= 88, 84)	2	3
General appearance: Week 20 (n= 4, 5)	1	1
General appearance: Week 24 (n= 5, 5)	0	0
General appearance: Week 28 (n= 2, 2)	0	0
General appearance: Week 32 (n= 2, 3)	0	0
General appearance: Week 40 (n= 1, 1)	0	0
General appearance: Week 44 (n= 59, 38)	1	0
Head: Week 18 (n= 88, 84	3	1
Head: Week 20 (n= 4, 5)	0	0
Head: Week 24 (n= 5,5)	0	0
Head: Week 28 (n= 2, 2)	0	0
Head: Week 32 (n= 2, 3)	0	1
Head: Week 40 (n= 1, 1)	1	0
Head: Week 44 (n= 59, 38)	0	0
Heart: Week 18 (n= 88, 84)	0	0
Heart: Week 20 (n= 87, 85)	0	0
Heart: Week 24 (n= 82, 73)	0	0
Heart: Week 28 (n= 75, 57)	0	0
Heart: Week 32 (n= 70, 52)	0	0
Heart: Week 36 (n= 66, 43)	0	0
Heart: Week 40 (n= 63, 41)	0	0
Heart: Week 44 (n= 59, 38)	0	0
Lungs: Week 18 (n= 88, 84)	0	0
Lungs: Week 20 (n= 87, 85)	1	0
Lungs: Week 24 (n= 82, 73)	1	0
Lungs: Week 28 (n= 75, 57)	1	0
Lungs: Week 32 (n= 70, 52)	0	0
Lungs: Week 36 (n= 66, 43)	0	0
Lungs: Week 40 (n= 63, 41)	0	1
Lungs: Week 44 (n= 59, 38)	0	0
Lymph nodes: Week 18 (n= 88, 84)	3	1
Lymph nodes: Week 20 (n= 87, 85)	3	0
Lymph nodes: Week 24 (n= 82, 73)	2	1
Lymph nodes: Week 28 (n= 75, 57)	1	0
Lymph nodes: Week 32 (n= 70, 52)	1	1
Lymph nodes: Week 36 (n= 66, 43)	1	0
Lymph nodes: Week 40 (n= 63, 41)	2	0
Lymph nodes: Week 44 (n= 59, 38)	1	1
Neurological: Week 18 (n= 88, 85)	3	1
Neurological: Week 20 (n= 4, 5)	1	0
Neurological: Week 24 (n= 5, 5)	0	0
Neurological: Week 28 (n= 2, 2)	0	0
Neurological: Week 32 (n= 2,3)	0	0
Neurological: Week 40 (n= 1, 1)	0	0
Neurological: Week 44 (n= 59, 38)	1	1
Nose: Week 18 (n= 88, 84)	4	0
Nose: Week 20 (n= 4, 5)	0	0
Nose: Week 24 (n= 5, 5)	0	0
Nose: Week 28 (n= 2, 2)	0	0
Nose: Week 32 (n= 2, 3)	0	0
Nose: Week 40 (n= 1, 1)	0	0
Nose: Week 44 (n= 59, 38)	1	0
Skin: Week 18 (n= 88, 84)	8	4
Skin: Week 20 (n= 4, 5)	3	1
Skin: Week 24 (n= 5, 5)	1	0
Skin: Week 28 (n= 2,2)	0	0
Skin: Week 32 (n= 2, 3)	0	0
Skin: Week 40 (n= 1, 1)	1	1
Skin: Week 44 (n= 59, 38)	4	2
Throat: Week 18 (n= 88, 84)	4	2
Throat: Week 20 (n= 4, 5)	0	1
Throat: Week 24 (n= 5, 5)	0	0
Throat: Week 28 (n= 2, 2)	0	0
Throat: Week 32 (n= 2, 3)	0	0
Throat: Week 40 (n= 1, 1)	0	0
Throat: Week 44 (n= 59, 38)	0	0

No statistical analyses for this end point

Secondary: Open-Label Phase: Number of Subjects With Vital Sign Abnormalities

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End point title

Open-Label Phase: Number of Subjects With Vital Sign Abnormalities

End point description

Vital Sign Abnormalities criteria included: sitting diastolic blood pressure (mmHG) of <50 mmHg, sitting pulse rate beats per minute (bpm) of <40 or 120 bpm, sitting systolic blood pressure (MMHG) of <90 mmHg, supine diastolic blood pressure (mmHG) of <50 mmHg, supine pulse rate (BPM) of <40 bpm or >120 bpm, supine systolic blood pressure (mmHG) of 90 mmHg. OLFAS: all subjects who were enrolled into OL phase and received at least 1 dose of study medication in OL phase. Here, “n” signifies subjects evaluable for this endpoint at specified time points.

End point type

Secondary

End point timeframe

From the first dose of study drug up to Week 18

End point values	Tofacitinib: Open-Label Phase
Number of subjects analysed	225
Units: subjects
Sitting diastolic BP: <50 mmHg (n= 219)	0
Sitting pulse rate: <40 bpm (n= 219)	0
Sitting pulse rate (bpm): >120 bpm (n= 219)	5
Sitting systolic BP (mmHg): <90 mmHg (n= 219)	0
Supine diastolic BP (mmHg): <50 mmHg (n= 28)	2
Supine pulse rate (bpm): <40 bpm (n= 28)	0
Supine pulse rate (bpm): >120 bpm (n= 28)	0
Supine systolic BP (mmHg): <90 mmHg (n= 28)	2

No statistical analyses for this end point

Secondary: Double Blind Phase: Number of Subjects With Vital Sign Abnormalities

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End point title

Double Blind Phase: Number of Subjects With Vital Sign Abnormalities

End point description

Vital Sign Abnormalities criteria included: diastolic blood pressure (mmHG) of <50 mmHg, Pulse rate (BPM) of <40 bpm or >120 bpm, sitting diastolic blood pressure (mmHG) of <50 mmHg, sitting pulse rate beats per minute (bpm) of <40 bpm or >120 bpm, sitting systolic blood pressure (mmHG) of <90 mmHg, supine diastolic blood pressure (MMHG) of <50 mmHg, supine pulse rate (BPM) of <40 bpm or >120 bpm, supine systolic blood pressure (mmHG) of <90 mmHg, systolic blood pressure (mmHG) of <90 mmHg. DBSAS: all subjects who have received atleast 1 dose of study medication in DB phase. Here, “n” signifies subjects evaluable for this endpoint at specified time points.

End point type

Secondary

End point timeframe

From the first dose of study drug in double blind up to week 44

End point values	Tofacitinib: Double Blind Phase	Placebo
Number of subjects analysed	87	82
Units: subjects
Diastolic BP (mmHg): <50 mmHg (n=1, 0)	0	0
Pulse rate (bpm): <40 bpm (n=1, 0)	0	0
Pulse rate (bpm): >120 bpm (n=1, 0)	0	0
Systolic BP (mmHg): <90 mmHg (n=86, 82)	0	0
Sitting diastolic BP (mmHg): <50 mmHg (n=86, 82)	0	0
Sitting pulse rate (bpm): <40 bpm (n=86, 82)	0	0
Sitting pulse rate (bpm): >120 bpm (n=87, 82)	0	1
Sitting systolic BP (mmHg): <90 mmHg (n=7, 8)	0	0
Supine diastolic BP (mmHg): <50 mmHg (n=7, 8)	0	0
Supine pulse rate (bpm): <40 bpm (n=7, 8)	0	0
Supine pulse rate (bpm): >120 bpm (n=7, 8)	0	0
Supine systolic BP (mmHg): <90 mmHg (n=1, 0)	1	0
Systolic BP (mmHg): <90 mmHg (n=1, 0)	0	0

No statistical analyses for this end point

Secondary: Open-Label Phase: Number of Subjects With Change From Baseline in Vital Sign Measures

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End point title

Open-Label Phase: Number of Subjects With Change From Baseline in Vital Sign Measures

End point description

Change in vital Signs included: Sitting diastolic blood pressure [mmHG]: >=20mmHg increase from baseline (IFB) and >= 20mmHg decrease from baseline (DFB). Sitting systolic blood pressure mmHG: >= 30mmHg IFB and >= 30mmHg DFB. Supine diastolic blood pressure mmHG: >= 20mmHg IFB and >= 20mmHg DFB. Supine systolic blood pressure mmHG: >= 30mmHg IFB and >= 30mmHg DFB. OLFAS: all subjects who were enrolled into OL phase and received at least 1 dose of study medication in OL phase. Here, “n” signifies subjects evaluable for this endpoint at specified time points.

End point type

Secondary

End point timeframe

From the first dose of study drug up to Week 18

End point values	Tofacitinib: Open-Label Phase
Number of subjects analysed	225
Units: subjects
Sitting diastolic BP:Chg >= 20mmHg increase(n=211)	9
Sitting diastolic BP:Chg >= 20mmHg decrease(n=211)	14
Sitting systolic BP:Chg >= 30mmHg increase(n=211)	2
Sitting systolic BP:Chg >= 30mmHg decrease(n=211)	5
Supine diastolic BP: Chg >= 20mmHg increase (n=14)	0
Supine diastolic BP: Chg >= 20mmHg decrease (n=14)	3
Supine systolic BP: Chg >= 30mmHg increase (n=14)	0
Supine systolic BP: Chg >= 30mmHg decrease (n=14)	3

No statistical analyses for this end point

Secondary: Double Blind Phase: Number of Subjects With Change From Baseline in Vital Sign Measures

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End point title

Double Blind Phase: Number of Subjects With Change From Baseline in Vital Sign Measures

End point description

Change in vital Signs included: Sitting diastolic blood pressure (mmHG): >=20mmHg IFB and >= 20mmHg DFB. Sitting systolic blood pressure mmHG: >= 30mmHg IFB and >= 30mmHg DFB. Supine diastolic blood pressure mmHG: >= 20mmHg IFB and >= 20mmHg DFB. Supine systolic blood pressure mmHG: >= 30mmHg IFB and >= 30mmHg DFB. DBSAS: all subjects who have received atleast 1 dose of study medication in DB phase. Here, N= subjects who were evaluable for this endpoint and “n” signifies subjects evaluable for this endpoint at specified time points.

End point type

Secondary

End point timeframe

From the first dose of study drug in double blind up to week 44

End point values	Tofacitinib: Double Blind Phase	Placebo
Number of subjects analysed	87	80
Units: subjects
Sitting diastolic BP:Chg >= 20 Increase (n=82, 79)	9	3
Sitting diastolic BP:Chg >=20 decrease (n=82, 79)	7	9
Sitting systolic BP: Chg>= 30 Increase (n=83, 79)	3	4
Sitting systolic BP:Chg >= 30 decrease (n=83, 79)	0	2
Supine diastolic BP:Chg >= 20 Increase (n=4, 5)	0	0
Supine diastolic BP:Chg >= 20 decrease(n=4, 5)	0	0
Supine systolic BP:Chg >= 30 Increase (n=4, 5)	0	0
Supine systolic BP:Chg >= 30 decrease(n=4, 5)	0	0

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

From the first dose of study drug up to week 44

Adverse event reporting additional description

Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 subject and as nonserious in another subject or 1 subject may have experienced both serious and nonserious event during study.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

22.0

Reporting group title

Tofacitinib: Double Blind Phase

Reporting group description

Reporting group title

Tofacitinib: Open-Label Phase

Reporting group description

Subjects received tofacitinib 5 mg tablets (for subjects >= 40 kg body weight) or tofacitinib 5 mL oral solution (for subjects < 40 kg body weight), BID, orally for 18 weeks in open-label phase.

Reporting group title

Placebo

Reporting group description

Serious adverse events	Tofacitinib: Double Blind Phase	Tofacitinib: Open-Label Phase	Placebo
Total subjects affected by serious adverse events
subjects affected / exposed	1 / 88 (1.14%)	7 / 225 (3.11%)	2 / 85 (2.35%)
number of deaths (all causes)	0	0	0
number of deaths resulting from adverse events	0	0	0
Surgical and medical procedures
Pilonidal sinus repair
subjects affected / exposed	1 / 88 (1.14%)	0 / 225 (0.00%)	0 / 85 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Condition aggravated
subjects affected / exposed	0 / 88 (0.00%)	1 / 225 (0.44%)	0 / 85 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Crohn's disease
subjects affected / exposed	0 / 88 (0.00%)	1 / 225 (0.44%)	0 / 85 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Diarrhoea
subjects affected / exposed	0 / 88 (0.00%)	1 / 225 (0.44%)	0 / 85 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Vomiting
subjects affected / exposed	0 / 88 (0.00%)	1 / 225 (0.44%)	0 / 85 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Intussusception
subjects affected / exposed	0 / 88 (0.00%)	0 / 225 (0.00%)	1 / 85 (1.18%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Still's disease
subjects affected / exposed	0 / 88 (0.00%)	1 / 225 (0.44%)	0 / 85 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Juvenile idiopathic arthritis
subjects affected / exposed	0 / 88 (0.00%)	0 / 225 (0.00%)	1 / 85 (1.18%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Infections and infestations
Appendicitis
subjects affected / exposed	0 / 88 (0.00%)	1 / 225 (0.44%)	1 / 85 (1.18%)
occurrences causally related to treatment / all	0 / 0	0 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Epidural empyema
subjects affected / exposed	0 / 88 (0.00%)	1 / 225 (0.44%)	0 / 85 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	0 / 88 (0.00%)	1 / 225 (0.44%)	0 / 85 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Sinusitis
subjects affected / exposed	0 / 88 (0.00%)	1 / 225 (0.44%)	0 / 85 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Subperiosteal abscess
subjects affected / exposed	0 / 88 (0.00%)	1 / 225 (0.44%)	0 / 85 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 2%

Non-serious adverse events	Tofacitinib: Double Blind Phase	Tofacitinib: Open-Label Phase	Placebo
Total subjects affected by non serious adverse events
subjects affected / exposed	57 / 88 (64.77%)	108 / 225 (48.00%)	57 / 85 (67.06%)
Investigations
Alanine aminotransferase increased
subjects affected / exposed	3 / 88 (3.41%)	6 / 225 (2.67%)	2 / 85 (2.35%)
occurrences all number	4	7	2
Aspartate aminotransferase increased
subjects affected / exposed	4 / 88 (4.55%)	7 / 225 (3.11%)	1 / 85 (1.18%)
occurrences all number	4	8	1
Blood creatine phosphokinase increased
subjects affected / exposed	3 / 88 (3.41%)	5 / 225 (2.22%)	1 / 85 (1.18%)
occurrences all number	3	5	1
Haemoglobin decreased
subjects affected / exposed	0 / 88 (0.00%)	0 / 225 (0.00%)	2 / 85 (2.35%)
occurrences all number	0	0	2
C-reactive protein increased
subjects affected / exposed	1 / 88 (1.14%)	0 / 225 (0.00%)	2 / 85 (2.35%)
occurrences all number	1	0	2
White blood cell count decreased
subjects affected / exposed	0 / 88 (0.00%)	0 / 225 (0.00%)	2 / 85 (2.35%)
occurrences all number	0	0	2
Nervous system disorders
Headache
subjects affected / exposed	2 / 88 (2.27%)	16 / 225 (7.11%)	6 / 85 (7.06%)
occurrences all number	2	21	8
General disorders and administration site conditions
Disease progression
subjects affected / exposed	8 / 88 (9.09%)	5 / 225 (2.22%)	13 / 85 (15.29%)
occurrences all number	8	5	13
Pyrexia
subjects affected / exposed	4 / 88 (4.55%)	11 / 225 (4.89%)	1 / 85 (1.18%)
occurrences all number	5	11	1
Condition aggravated
subjects affected / exposed	2 / 88 (2.27%)	0 / 225 (0.00%)	2 / 85 (2.35%)
occurrences all number	2	0	2
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	0 / 88 (0.00%)	5 / 225 (2.22%)	0 / 85 (0.00%)
occurrences all number	0	5	0
Lymphadenitis
subjects affected / exposed	1 / 88 (1.14%)	0 / 225 (0.00%)	2 / 85 (2.35%)
occurrences all number	1	0	2
Leukopenia
subjects affected / exposed	0 / 88 (0.00%)	0 / 225 (0.00%)	2 / 85 (2.35%)
occurrences all number	0	0	2
Ear and labyrinth disorders
Ear pain
subjects affected / exposed	2 / 88 (2.27%)	0 / 225 (0.00%)	1 / 85 (1.18%)
occurrences all number	2	0	1
Eye disorders
Uveitis
subjects affected / exposed	0 / 88 (0.00%)	0 / 225 (0.00%)	2 / 85 (2.35%)
occurrences all number	0	0	2
Gastrointestinal disorders
Abdominal pain upper
subjects affected / exposed	0 / 88 (0.00%)	5 / 225 (2.22%)	0 / 85 (0.00%)
occurrences all number	0	5	0
Nausea
subjects affected / exposed	0 / 88 (0.00%)	13 / 225 (5.78%)	0 / 85 (0.00%)
occurrences all number	0	13	0
Diarrhoea
subjects affected / exposed	1 / 88 (1.14%)	5 / 225 (2.22%)	2 / 85 (2.35%)
occurrences all number	1	6	2
Abdominal pain
subjects affected / exposed	0 / 88 (0.00%)	8 / 225 (3.56%)	3 / 85 (3.53%)
occurrences all number	0	8	3
Vomiting
subjects affected / exposed	0 / 88 (0.00%)	12 / 225 (5.33%)	4 / 85 (4.71%)
occurrences all number	0	14	5
Dyspepsia
subjects affected / exposed	2 / 88 (2.27%)	0 / 225 (0.00%)	1 / 85 (1.18%)
occurrences all number	2	0	1
Respiratory, thoracic and mediastinal disorders
Epistaxis
subjects affected / exposed	3 / 88 (3.41%)	0 / 225 (0.00%)	1 / 85 (1.18%)
occurrences all number	3	0	1
Cough
subjects affected / exposed	2 / 88 (2.27%)	7 / 225 (3.11%)	1 / 85 (1.18%)
occurrences all number	3	9	2
Nasal congestion
subjects affected / exposed	2 / 88 (2.27%)	0 / 225 (0.00%)	1 / 85 (1.18%)
occurrences all number	2	0	1
Oropharyngeal pain
subjects affected / exposed	2 / 88 (2.27%)	0 / 225 (0.00%)	3 / 85 (3.53%)
occurrences all number	2	0	3
Skin and subcutaneous tissue disorders
Rash
subjects affected / exposed	2 / 88 (2.27%)	0 / 225 (0.00%)	0 / 85 (0.00%)
occurrences all number	2	0	0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	2 / 88 (2.27%)	5 / 225 (2.22%)	4 / 85 (4.71%)
occurrences all number	2	5	4
Arthritis
subjects affected / exposed	1 / 88 (1.14%)	0 / 225 (0.00%)	3 / 85 (3.53%)
occurrences all number	1	0	3
Back pain
subjects affected / exposed	3 / 88 (3.41%)	5 / 225 (2.22%)	1 / 85 (1.18%)
occurrences all number	3	6	1
Juvenile idiopathic arthritis
subjects affected / exposed	3 / 88 (3.41%)	6 / 225 (2.67%)	11 / 85 (12.94%)
occurrences all number	3	6	11
Pain in extremity
subjects affected / exposed	1 / 88 (1.14%)	0 / 225 (0.00%)	2 / 85 (2.35%)
occurrences all number	1	0	3
Infections and infestations
Gastroenteritis
subjects affected / exposed	2 / 88 (2.27%)	0 / 225 (0.00%)	0 / 85 (0.00%)
occurrences all number	2	0	0
Nasopharyngitis
subjects affected / exposed	7 / 88 (7.95%)	10 / 225 (4.44%)	3 / 85 (3.53%)
occurrences all number	7	14	3
Influenza
subjects affected / exposed	3 / 88 (3.41%)	8 / 225 (3.56%)	2 / 85 (2.35%)
occurrences all number	3	8	2
Pharyngitis streptococcal
subjects affected / exposed	2 / 88 (2.27%)	5 / 225 (2.22%)	0 / 85 (0.00%)
occurrences all number	3	5	0
Pharyngitis
subjects affected / exposed	2 / 88 (2.27%)	5 / 225 (2.22%)	1 / 85 (1.18%)
occurrences all number	2	5	1
Respiratory tract infection
subjects affected / exposed	3 / 88 (3.41%)	0 / 225 (0.00%)	1 / 85 (1.18%)
occurrences all number	3	0	1
Respiratory tract infection viral
subjects affected / exposed	1 / 88 (1.14%)	0 / 225 (0.00%)	2 / 85 (2.35%)
occurrences all number	1	0	2
Rhinitis
subjects affected / exposed	2 / 88 (2.27%)	0 / 225 (0.00%)	1 / 85 (1.18%)
occurrences all number	2	0	1
Sinusitis
subjects affected / exposed	4 / 88 (4.55%)	0 / 225 (0.00%)	1 / 85 (1.18%)
occurrences all number	4	0	1
Tonsillitis
subjects affected / exposed	1 / 88 (1.14%)	0 / 225 (0.00%)	2 / 85 (2.35%)
occurrences all number	1	0	2
Upper respiratory tract infection
subjects affected / exposed	13 / 88 (14.77%)	24 / 225 (10.67%)	9 / 85 (10.59%)
occurrences all number	15	30	10
Urinary tract infection
subjects affected / exposed	1 / 88 (1.14%)	0 / 225 (0.00%)	3 / 85 (3.53%)
occurrences all number	1	0	3
Viral infection
subjects affected / exposed	2 / 88 (2.27%)	5 / 225 (2.22%)	1 / 85 (1.18%)
occurrences all number	3	5	1
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	0 / 88 (0.00%)	6 / 225 (2.67%)	0 / 85 (0.00%)
occurrences all number	0	6	0

More information

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Were there any global substantial amendments to the protocol? No

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

Data not reported for the PK endpoint, since the PK dataset will be combined with PK from other studies to enable the analysis, the results of this pooled analysis will be reported separately.

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Clinical trials

Clinical Trial Results: Efficacy, safety and tolerability of tofacitinib for Treatment of polyarticular course juvenile idiopathic Arthritis (jia) in children and adolescent subjects

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Double Blind Phase: Percentage of Subjects With Disease Flare According to Pediatric Rheumatology Collaborative Study Group/Pediatric Rheumatology International Trials Organization (PRCSG/PRINTO) Disease Flare Criteria at Week 44

Primary: Double Blind Phase: Percentage of Subjects With Disease Flare According to Pediatric Rheumatology Collaborative Study Group/Pediatric Rheumatology International Trials Organization (PRCSG/PRINTO) Disease Flare Criteria at Week 44

Secondary: Double Blind Phase: Percentage of Subjects With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 50 Response at Week 44

Secondary: Double Blind Phase: Percentage of Subjects With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 50 Response at Week 44

Secondary: Double Blind Phase: Percentage of Subjects With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 30 Response at Week 44

Secondary: Double Blind Phase: Percentage of Subjects With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 30 Response at Week 44

Secondary: Double Blind Phase: Percentage of Subjects With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 70 Response at Week 44

Secondary: Double Blind Phase: Percentage of Subjects With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 70 Response at Week 44

Secondary: Double Blind Phase: JIA ACR Core Variable- Change from Double-Blind Baseline in Childhood Health Assessment Questionnaire (CHAQ)- Disability Index at Week 44

Secondary: Double Blind Phase: JIA ACR Core Variable- Change from Double-Blind Baseline in Childhood Health Assessment Questionnaire (CHAQ)- Disability Index at Week 44

Secondary: Open-Label Phase: Percentage of Subjects With Disease Flare According to Pediatric Rheumatology Collaborative Study Group/Pediatric Rheumatology International Trials Organization (PRCSG/PRINTO) Disease Flare criteria at Week 2, 4, 8, 12 and 18

Secondary: Open-Label Phase: Percentage of Subjects With Disease Flare According to Pediatric Rheumatology Collaborative Study Group/Pediatric Rheumatology International Trials Organization (PRCSG/PRINTO) Disease Flare criteria at Week 2, 4, 8, 12 and 18

Secondary: Double Blind Phase: Percentage of Subjects According to Pediatric Rheumatology Collaborative Study Group/Pediatric Rheumatology International Trials Organization (PRCSG/PRINTO) Disease Flare Criteria With Disease Flare at Weeks 20, 24, 28, 32, 36 and 40

Secondary: Double Blind Phase: Percentage of Subjects According to Pediatric Rheumatology Collaborative Study Group/Pediatric Rheumatology International Trials Organization (PRCSG/PRINTO) Disease Flare Criteria With Disease Flare at Weeks 20, 24, 28, 32, 36 and 40

Secondary: Open-Label Phase: Time to Disease Flare

Secondary: Open-Label Phase: Time to Disease Flare

Secondary: Double Blind Phase: Time to Disease Flare

Secondary: Double Blind Phase: Time to Disease Flare

Secondary: Open-Label Phase: Percentage of Subjects With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 30 Response at Weeks 2, 4, 8, 12 and 18

Secondary: Open-Label Phase: Percentage of Subjects With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 30 Response at Weeks 2, 4, 8, 12 and 18

Secondary: Double Blind Phase: Percentage of Subjects With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 30 Response at Double Blind Baseline, Week 20, 24, 28, 32, 36 and 40

Secondary: Double Blind Phase: Percentage of Subjects With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 30 Response at Double Blind Baseline, Week 20, 24, 28, 32, 36 and 40

Secondary: Open-Label Phase: Percentage of Subjects With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 50 Response at Week 2, 4, 8, 12 and 18

Secondary: Open-Label Phase: Percentage of Subjects With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 50 Response at Week 2, 4, 8, 12 and 18

Secondary: Double Blind Phase: Percentage of Subjects With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 50 Response at Double Blind Baseline, Week 20, 24, 28, 32, 36 and 40

Secondary: Double Blind Phase: Percentage of Subjects With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 50 Response at Double Blind Baseline, Week 20, 24, 28, 32, 36 and 40

Secondary: Open-Label Phase: Percentage of Subjects With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 70 Response at Week 2, 4, 8, 12 and 18

Secondary: Open-Label Phase: Percentage of Subjects With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 70 Response at Week 2, 4, 8, 12 and 18

Secondary: Double Blind Phase: Percentage of Subjects With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 70 Response at Double Blind Baseline (Week 18), Week 20, 24, 28, 32, 36 and 40

Secondary: Double Blind Phase: Percentage of Subjects With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 70 Response at Double Blind Baseline (Week 18), Week 20, 24, 28, 32, 36 and 40

Secondary: Open-Label Phase: Percentage of Subjects With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 90 Response at Week 2, 4, 8, 12 and 18

Secondary: Open-Label Phase: Percentage of Subjects With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 90 Response at Week 2, 4, 8, 12 and 18

Secondary: Double Blind Phase: Percentage of Subjects With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 90 Response at Double Blind Baseline, Week 20, 24, 28, 32, 36, 40 and 44

Secondary: Double Blind Phase: Percentage of Subjects With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 90 Response at Double Blind Baseline, Week 20, 24, 28, 32, 36, 40 and 44

Secondary: Open-Label Phase: Percentage of Subjects With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 100 Response at Week 2, 4, 8, 12 and 18

Secondary: Open-Label Phase: Percentage of Subjects With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 100 Response at Week 2, 4, 8, 12 and 18

Secondary: Double Blind Phase: Percentage of Subjects With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 100 Response at Double Blind Baseline, Week 20, 24, 28, 32, 36, 40 and 44

Secondary: Double Blind Phase: Percentage of Subjects With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 100 Response at Double Blind Baseline, Week 20, 24, 28, 32, 36, 40 and 44

Secondary: Open Label Phase: Change From Baseline in Juvenile Arthritis Disease Activity Score (JADAS) 27 C-Reactive Protein (CRP) Score at Week 2, 4, 8, 12 and 18

Secondary: Open Label Phase: Change From Baseline in Juvenile Arthritis Disease Activity Score (JADAS) 27 C-Reactive Protein (CRP) Score at Week 2, 4, 8, 12 and 18

Secondary: Double Blind Phase: Change from Double-Blind Baseline in Juvenile Arthritis Disease Activity Score (JADAS) 27 C-Reactive Protein (CRP) Score at Week 20, 24, 28, 32, 36, 40 and 44

Secondary: Double Blind Phase: Change from Double-Blind Baseline in Juvenile Arthritis Disease Activity Score (JADAS) 27 C-Reactive Protein (CRP) Score at Week 20, 24, 28, 32, 36, 40 and 44

Secondary: Open Label Phase: Change From Baseline in JADAS-27 Erythrocyte Sedimentation Rate (ESR) Score at Week 2, 4, 8, 12 and 18

Secondary: Open Label Phase: Change From Baseline in JADAS-27 Erythrocyte Sedimentation Rate (ESR) Score at Week 2, 4, 8, 12 and 18

Secondary: Double Blind Phase: Change from Double-Blind Baseline in JADAS-27 Erythrocyte Sedimentation Rate (ESR) Score at Week 20, 24, 28, 32, 36, 40 and 44

Secondary: Double Blind Phase: Change from Double-Blind Baseline in JADAS-27 Erythrocyte Sedimentation Rate (ESR) Score at Week 20, 24, 28, 32, 36, 40 and 44

Secondary: Open-Label Phase: Percentage of Subjects With JADAS-27 CRP Minimum Disease Activity at Week 2, 4, 8, 12 and 18

Secondary: Open-Label Phase: Percentage of Subjects With JADAS-27 CRP Minimum Disease Activity at Week 2, 4, 8, 12 and 18

Secondary: Double Blind Phase: Percentage of Subjects With JADAS-27 CRP Minimum Disease Activity at Double Blind Baseline, Week 20, 24, 28, 32, 36, 40 and 44

Secondary: Double Blind Phase: Percentage of Subjects With JADAS-27 CRP Minimum Disease Activity at Double Blind Baseline, Week 20, 24, 28, 32, 36, 40 and 44

Secondary: Open-Label Phase: Percentage of Subjects With JADAS CRP Inactive Disease Activity at Week 2, 4, 8, 12 and 18

Secondary: Open-Label Phase: Percentage of Subjects With JADAS CRP Inactive Disease Activity at Week 2, 4, 8, 12 and 18

Secondary: Double Blind Phase: Percentage of Subjects With JADAS CRP Inactive Disease Activity at Double Blind Baseline, Week 20, 24, 28, 32, 36, 40 and 44

Secondary: Double Blind Phase: Percentage of Subjects With JADAS CRP Inactive Disease Activity at Double Blind Baseline, Week 20, 24, 28, 32, 36, 40 and 44

Secondary: Double Blind Phase: Percentage of Subjects With JIA ACR Inactive Disease at Week 20, 24, 28, 32, 36, 40 and 44

Secondary: Double Blind Phase: Percentage of Subjects With JIA ACR Inactive Disease at Week 20, 24, 28, 32, 36, 40 and 44

Secondary: Double Blind Phase: Percentage of Subjects With Presence of JIA ACR Clinical Remission

Secondary: Double Blind Phase: Percentage of Subjects With Presence of JIA ACR Clinical Remission

Secondary: Open Label Phase: JIA ACR Core Variable- Change From Baseline in Number of Joints With Active Arthritis at Week 2, 4, 8, 12 and 18

Secondary: Open Label Phase: JIA ACR Core Variable- Change From Baseline in Number of Joints With Active Arthritis at Week 2, 4, 8, 12 and 18

Secondary: Double Blind Phase: JIA ACR Core Variable- Change from Double-Blind Baseline in Number of Joints With Active Arthritis at Week 20, 24, 28, 32, 36, 40 and 44

Secondary: Double Blind Phase: JIA ACR Core Variable- Change from Double-Blind Baseline in Number of Joints With Active Arthritis at Week 20, 24, 28, 32, 36, 40 and 44

Secondary: Open Label Phase: JIA ACR Core Variable- Change From Baseline in Number of Joints With Limited Range of Motion at Week 2, 4, 8, 12 and 18

Secondary: Open Label Phase: JIA ACR Core Variable- Change From Baseline in Number of Joints With Limited Range of Motion at Week 2, 4, 8, 12 and 18

Secondary: Double Blind Phase: JIA ACR Core Variable- Change From Double-Blind Baseline in Number of Joints With Limited Range of Motion at Double Blind Baseline (Week 18), Week 20, 24, 28, 32, 36, 40 and 44

Secondary: Double Blind Phase: JIA ACR Core Variable- Change From Double-Blind Baseline in Number of Joints With Limited Range of Motion at Double Blind Baseline (Week 18), Week 20, 24, 28, 32, 36, 40 and 44

Secondary: Open Label Phase: JIA ACR Core Variable- Change From Baseline in Physician Global Evaluation of Disease Activity at Week 2, 4, 8, 12 and 18

Secondary: Open Label Phase: JIA ACR Core Variable- Change From Baseline in Physician Global Evaluation of Disease Activity at Week 2, 4, 8, 12 and 18

Secondary: Double Blind Phase: JIA ACR Core Variable-Change from Double-Blind Baseline in Physician Global Evaluation of Disease Activity at Week 20, 24, 28, 32, 36, 40 and 44

Secondary: Double Blind Phase: JIA ACR Core Variable-Change from Double-Blind Baseline in Physician Global Evaluation of Disease Activity at Week 20, 24, 28, 32, 36, 40 and 44

Clinical Trial Results:
Efficacy, safety and tolerability of tofacitinib for Treatment of polyarticular course juvenile idiopathic Arthritis (jia) in children and adolescent subjects