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Clinical Trial Results:
A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Study of the Efficacy and Safety of Tofacitinib in Subjects With Active Ankylosing Spondylitis (AS)

Summary
EudraCT number	2018-000226-58
Trial protocol	FR HU CZ ES AT GB DE BG
Global end of trial date	20 Aug 2020

Results information
Results version number	v1(current)
This version publication date	04 Sep 2021
First version publication date	04 Sep 2021
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

A3921120

ISRCTN number

US NCT number

NCT03502616

WHO universal trial number (UTN)

Other trial identifiers

Alias ID: AS

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)

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

15 Dec 2020

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

20 Aug 2020

Was the trial ended prematurely?

Main objective of the trial

To compare the efficacy of tofacitinib 5 milligrams (mg) twice daily (BID) versus placebo on the Ankylosing Spondylitis Disease Activity Score (ASAS)20 response rate at Week 16 in subjects with active ankylosing spondylitis (AS) that have had an inadequate response to previous treatment.

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 Harmonisation (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

07 Jun 2018

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Australia: 3

Country: Number of subjects enrolled

Bulgaria: 6

Country: Number of subjects enrolled

Canada: 10

Country: Number of subjects enrolled

China: 45

Country: Number of subjects enrolled

Czechia: 40

Country: Number of subjects enrolled

France: 1

Country: Number of subjects enrolled

Hungary: 5

Country: Number of subjects enrolled

Korea, Republic of: 8

Country: Number of subjects enrolled

Poland: 54

Country: Number of subjects enrolled

Russian Federation: 27

Country: Number of subjects enrolled

Turkey: 12

Country: Number of subjects enrolled

Ukraine: 41

Country: Number of subjects enrolled

United States: 17

Worldwide total number of subjects

269

EEA total number of subjects

106

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)

Adults (18-64 years)

263

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

The study was conducted at 13 countries between 07 June 2018 and 20 August 2020. 270 subjects were enrolled in the study out of which 269 received treatment.

Screening details

Safety data was planned to be collected and reported for both: Week 0 to Week 16 and from Week 0 to Week 48.

Period 1 title

Up to Week 16

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

Tofacitinib

Arm description

Subjects received Tofacitinib tablets 5 milligram (mg), twice daily for 48 weeks.

Arm type

Experimental

Investigational medicinal product name

Tofacitinib

Investigational medicinal product code

CP-690,550

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Tofacitinib tablets 5 milligram (mg), twice daily for 16 weeks.

Placebo Then Tofacitinib

Arm description

Subjects received tofacitinib matching placebo tablets, twice daily for 16 weeks followed by tofacitinib tablets 5 mg, twice daily for next 32 weeks (i.e. up to Week 48).

Arm type

Placebo

Investigational medicinal product name

Tofacitinib matching placebo tablets

Investigational medicinal product code

Other name

Pharmaceutical forms

Coated tablet

Routes of administration

Oral use

Dosage and administration details

Matching placebo tablets, twice daily for 16 weeks

Number of subjects in period 1	Tofacitinib	Placebo Then Tofacitinib
Started	133	136
Completed	132	133
Not completed	1	3
Consent withdrawn by subject	1	2
Lost to follow-up	-	1

Period 2 title

Week 16 to Week 48

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Tofacitinib

Arm description

Subjects received Tofacitinib tablets 5 milligram (mg), twice daily for 48 weeks.

Arm type

Experimental

Investigational medicinal product name

Tofacitinib

Investigational medicinal product code

CP-690,550

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Tofacitinib tablets 5 mg, twice daily for 32 weeks.

Placebo Then Tofacitinib

Arm description

Subjects received tofacitinib matching placebo tablets, twice daily for 16 weeks followed by tofacitinib tablets 5 mg, twice daily for next 32 weeks (i.e. up to Week 48).

Arm type

Placebo

Investigational medicinal product name

Tofacitinib

Investigational medicinal product code

CP-690,550

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Tofacitinib tablets 5 mg, twice daily for 32 weeks

Number of subjects in period 2	Tofacitinib	Placebo Then Tofacitinib
Started	132	133
Treated	132	133
Completed	125	127
Not completed	7	6
Consent withdrawn by subject	6	6
Lost to follow-up	1	-

Baseline characteristics

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Reporting group title

Tofacitinib

Reporting group description

Subjects received Tofacitinib tablets 5 milligram (mg), twice daily for 48 weeks.

Reporting group title

Placebo Then Tofacitinib

Reporting group description

Subjects received tofacitinib matching placebo tablets, twice daily for 16 weeks followed by tofacitinib tablets 5 mg, twice daily for next 32 weeks (i.e. up to Week 48).

Reporting group values	Tofacitinib	Placebo Then Tofacitinib	Total
Number of subjects	133	136	269
Age categorical
Units: Subjects
Adults (18-64 years)	127	136	263
From 65-84 years	6	0	6
Age Continuous
Units: Years
arithmetic mean (standard deviation)	42.2 ( 11.85 )	40.0 ( 11.06 )	-
Sex: Female, Male
Units: Subjects
Female	17	28	45
Male	116	108	224
Race/Ethnicity, Customized
Units: Subjects
White	107	106	213
Asian	25	30	55
Not reported	1	0	1

End points

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Reporting group title

Tofacitinib

Reporting group description

Subjects received Tofacitinib tablets 5 milligram (mg), twice daily for 48 weeks.

Reporting group title

Placebo Then Tofacitinib

Reporting group description

Subjects received tofacitinib matching placebo tablets, twice daily for 16 weeks followed by tofacitinib tablets 5 mg, twice daily for next 32 weeks (i.e. up to Week 48).

Reporting group title

Tofacitinib

Reporting group description

Subjects received Tofacitinib tablets 5 milligram (mg), twice daily for 48 weeks.

Reporting group title

Placebo Then Tofacitinib

Reporting group description

Subjects received tofacitinib matching placebo tablets, twice daily for 16 weeks followed by tofacitinib tablets 5 mg, twice daily for next 32 weeks (i.e. up to Week 48).

Subject analysis set title

Up to Week 48 Tofacitinib

Subject analysis set type

Full analysis

Subject analysis set description

Subjects received tofacitinib 5 mg tablets twice daily for 48 weeks.

Subject analysis set title

Up to Week 48 Placebo Then Tofacitinib

Subject analysis set type

Full analysis

Subject analysis set description

Subjects received tofacitinib matching placebo tablets, twice daily for 16 weeks followed by tofacitinib tablets 5 mg, twice daily for next 32 weeks (i.e. up to Week 48).

Subject analysis set title

Tofacitinib

Subject analysis set type

Full analysis

Subject analysis set description

Participants received Tofacitinib tablets 5 milligram (mg), twice daily for 48 weeks.

Subject analysis set title

Placebo Then Tofacitinib

Subject analysis set type

Full analysis

Subject analysis set description

Participants received tofacitinib matching placebo tablets, twice daily for 16 weeks followed by tofacitinib tablets 5 mg, twice daily for next 32 weeks (i.e. up to Week 48).

Primary: Percentage of Subjects Achieving Assessment of SpondyloArthritis International Society (ASAS)20 Response at Week 16

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End point title

Percentage of Subjects Achieving Assessment of SpondyloArthritis International Society (ASAS)20 Response at Week 16

End point description

ASAS20 assess 4 domain:Patient Global Assessment of Disease (PGA) (scale:0[not active]-10[very active], high score=more disease activity), total back pain (scale:0[no pain]-10[most severe pain], high score=more severity), Function (Bath Ankylosing Spondylitis Functional Index [BASFI]; subject’s level of ability: scale:0[easy]-10[impossible], low score=better functional health), Inflammation (morning stiffness, Mean of Question [Q]5, Q6 of Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]:6-item questionnaire measure disease activity:scale:0[none]-10[severe], high score=more disease activity). ASAS20 response: >= 20% improvement from baseline in disease activity, absolute change of >=1 unit in >=3 domains, no worsening of >=20%, absolute change of >=1 unit in remaining domain. FAS:all subject randomised to study, received at least one dose of investigational product (tofacitinib or placebo). On-drug data used, missing response (MR) considered to be Non-response (NR) (MR=NR).

End point type

Primary

End point timeframe

Week 16

End point values	Tofacitinib	Placebo Then Tofacitinib
Number of subjects analysed	133	136
Units: Percentage of subjects
number (not applicable)	56.39	29.41

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via Cochran–Mantel–Haenszel (CMH) approach.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

269

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

27.08

Confidence interval

level

95%

sides

2-sided

lower limit

15.89

upper limit

38.28

Variability estimate

Standard error of the mean

Dispersion value

5.71

Secondary: Percentage of Subjects Achieving Ankylosing Spondylitis (ASAS)40 Response at Week 16

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End point title

Percentage of Subjects Achieving Ankylosing Spondylitis (ASAS)40 Response at Week 16

End point description

ASAS40 assessed 4 domains: the “PGA” (assess disease activity on a scale of 0 [not active] to 10 [very active], higher score=more disease activity), total back pain (on a scale of 0 [no pain] to 10 [most severe pain], higher score=more severity), Function (from BASFI: assess subject’s level of ability on a scale of 0 [easy] to 10 [impossible], lower scores= better functional health) and Inflammation (morning stiffness, Mean of Q5 and Q6 of BASDAI defined as 6 item questionnaire: measures disease activity on a scale of 0 [none] to 10 [severe], higher score=more disease activity). ASAS40 response: >=40% and >=2 units improvement in >=3 domains and no worsening at all in the remaining domain. FAS: included all subjects who were randomised to the study and received at least one dose of the randomised investigational product (i.e., tofacitinib or placebo). Here, on-drug data was used and MR was considered to be NR (MR=NR).

End point type

Secondary

End point timeframe

Week 16

End point values	Tofacitinib	Placebo Then Tofacitinib
Number of subjects analysed	133	136
Units: Percentage of subjects
number (not applicable)	40.60	12.50

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

269

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

28.17

Confidence interval

level

95%

sides

2-sided

lower limit

18.26

upper limit

38.09

Variability estimate

Standard error of the mean

Dispersion value

5.06

Secondary: Number of Subjects With Treatment Emergent Adverse Events (AEs)

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End point title

Number of Subjects With Treatment Emergent Adverse Events (AEs)

End point description

AE:any untoward medical occurrence in subject who received study drug without regard to possibility of causal relationship. Per National Cancer Institute - Common Terminology Criteria for AEs (NCI-CTCAE) version 4.03, severity:Grade 1:asymptomatic/mild symptom, clinical/diagnostic observation only, intervention not indicated; Grade 2:moderate, minimal, local/noninvasive intervention indicated, limiting age-appropriate instrumental activity of daily living (ADL); Grade 3:severe/medically significant but not immediately life-threatening, hospitalisation/prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4:life-threatening consequence, urgent intervention indicated; Grade 5:death. Treatment-emergent AEs: from first dose up to 48 week that were absent before treatment/worsened relative to pretreatment state. Safety analysis set: include all subject who were randomised, received at least one dose of investigational product (tofacitinib or placebo)

End point type

Secondary

End point timeframe

Baseline up to Week 16 and Baseline up to Week 48

End point values	Tofacitinib	Placebo Then Tofacitinib
Number of subjects analysed	133	136
Units: Subjects
Up to Week 16	73	70
Up to Week 48	103	93

No statistical analyses for this end point

Secondary: Number of Subjects With Treatment Emergent Adverse Events (AEs) by Severity

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End point title

Number of Subjects With Treatment Emergent Adverse Events (AEs) by Severity

End point description

AE: any untoward medical occurrence in subject who receive study drug without regard to possibility of causal relationship. Treatment-emergent AEs were events that occurred between first dose of study drug and up to 48 weeks that were absent before treatment or that worsened relative to pretreatment state. The severity grades (mild, moderate and severe) were defined as - mild: did not interfere with subject's usual function, moderate: Interfered to some extent with subject's usual function and severe: Interfered significantly with subject's usual function. Safety analysis set: included all subjects who were randomised and received at least one dose of the investigational product (i.e., tofacitinib or placebo).

End point type

Secondary

End point timeframe

Baseline up to Week 16 and Baseline up to Week 48

End point values	Tofacitinib	Placebo Then Tofacitinib
Number of subjects analysed	133	136
Units: Subjects
Up to Week 16: Mild	53	52
Up to Week 16: Moderate	18	18
Up to Week 16: Severe	2	0
Up to Week 48: Mild	57	57
Up to Week 48: Moderate	40	36
Up to Week 48: Severe	6	0

No statistical analyses for this end point

Secondary: Number of Subjects With Laboratory Abnormalities (Without Regard to Baseline Abnormality)

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End point title

Number of Subjects With Laboratory Abnormalities (Without Regard to Baseline Abnormality)

End point description

Hematology(Hemoglobin,Hematocrit,Erythrocyte[Ery],Lymphocyte/Leukocyte,Neutrophil/Leukocyte<0.8*LLN,Reticulocyte>1.5*ULN, Ery Mean Corpuscular Volume,Ery. Mean Corpuscular Hemoglobin,Ery. Mean Corpuscular HGB Concentration<0.9*LLN,>1.1*ULN,Reticulocyte/Ery,Leukocyte>1.5*ULN,Lymphocyte,Neutrophil<0.8*LLN and >1.2*ULN,Basophil,Basophil/Leukocyte,Eosinophil,Eosinophil/Leukocyte,Monocyte,Monocyte/Leukocyte>1.2*ULN); Clinical Chemistry(Bilirubin,Glucose>1.5*ULN,AST,ALT,Gamma Glutamyl Transferase>3.0*ULN,Urea,Creatinine, Triglyceride,Cholesterol>1.3*ULN,LDL Cholesterol>1.2*ULN,Potassium,C Reactive Protein>1.1*ULN,Bicarbonate<0.9*LLN,Creatine Kinase>2.0*ULN,HDL Cholesterol<0.8*LLN),Urinalysis(Specific Gravity>1.035,pH>8,Glucose,Ketones,Protein,Hemoglobin>=1,Ery,Leukocyte>=20,Granular Cast,Hyaline Cast>1. Safety analysis set:include all subject randomise,receive >=1 dose of investigational product(tofacitinib or placebo).Number of subject analyse signify subject analysed for this end point.

End point type

Secondary

End point timeframe

Baseline up to Week 16 and Baseline up to Week 48

End point values	Tofacitinib	Placebo Then Tofacitinib
Number of subjects analysed	132	136
Units: Subjects
Up to Week 16	106	129
Up to Week 48	126	131

No statistical analyses for this end point

Secondary: Number of Subjects With Vital Signs Abnormalities

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End point title

Number of Subjects With Vital Signs Abnormalities

End point description

Criteria for abnormalities in vital signs: Pulse rate <40 beats per minute (bpm) to >120 bpm, Sitting Diastolic blood pressure (DBP) < 50 millimetre of mercury (mmHg), increase and decrease in change from baseline of >= 20mmHg, sitting systolic blood pressure (SBP) < 90 mmHg, increase and decrease in change from baseline of >= 30mmHg. Safety analysis set: included all subjects who were randomised and received at least one dose of the investigational product (i.e., tofacitinib or placebo). Here "number of subjects analysed" signifies subjects analysed for this end point.

End point type

Secondary

End point timeframe

Baseline up to Week 16 and Baseline up to Week 48

End point values	Tofacitinib	Placebo Then Tofacitinib
Number of subjects analysed	132	136
Units: Subjects
Up to Week 16, Pulse rate: <40 bpm	0	0
Up to Week 16, Pulse rate: >120 bpm	0	0
Up to Week 16, Sitting DBP: <50 mmHg	0	0
Up to Week 16,Sitting DBP:Change>=20mmHg increase	2	4
Up to Week 16,Sitting DBP:Change>=20mmHg decrease	6	4
Up to Week 16, Sitting SBP <90mmHg	1	0
Up to Week 16,Sitting SBP:Change>=30mmHg increase	2	4
Up to Week 16,Sitting SBP:Change>=30mmHg decrease	2	5
Up to Week 48, Pulse rate: <40 bpm	0	0
Up to Week 48, Pulse rate: >120 bpm	0	1
Up to Week 48, Sitting DBP: <50 mmHg	0	0
Up to Week 48,Sitting DBP:Change>=20mmHg increase	5	8
Up to Week 48,Sitting DBP:Change>= 20mmHg decrease	11	8
Up to Week 48, Sitting SBP: <90mmHg	1	0
Up to Week 48,Sitting SBP:Change>= 30mmHg increase	5	5
Up to Week 48,Sitting SBP:Change>= 30mmHg decrease	5	7

No statistical analyses for this end point

Secondary: Number of Subjects with Abnormalities in Physical Examination

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End point title

Number of Subjects with Abnormalities in Physical Examination

End point description

Complete physical examination: included general appearance, skin (presence of rash), heent (head, eyes, ears, nose and throat), lungs (auscultation), heart (auscultation for presence of murmurs, gallops, rubs), lower extremities (presence of peripheral edema), abdominal (palpation and auscultation), neurologic (mental status, station, gait, reflexes, motor and sensory function, coordination) and lymph nodes. Abnormalities in physical examination was based on investigator's discretion/clinical judgement. Safety analysis set: included all subjects who were randomised and received at least one dose of the investigational product (i.e., tofacitinib or placebo). Here, ‘n’= subjects analysed for this end point for specified rows.

End point type

Secondary

End point timeframe

Screening, Week 16, and Week 48

End point values	Tofacitinib	Placebo Then Tofacitinib
Number of subjects analysed	133	136
Units: Subjects
Abdomen: Screening (n=133, 135)	2	1
Abdomen: Week 16 (n=132, 132)	1	2
Abdomen: Week 48 (n=119, 119)	1	1
Extremities: Screening (n=133, 136)	17	15
Extremities: Week 16 (n=132, 132)	8	14
Extremities: Week 48 (n=119, 119)	4	7
General appearance: Screening (n=133, 135)	10	11
General appearance: Week 16 (n=132, 132)	9	9
General appearance: Week 48 (n=119,119)	7	6
Heent: Screening (n=133,135)	5	7
Heent: Week 16 (n=132, 132)	4	7
Heent: Week 48 (n=119, 119)	3	7
Heart: Screening (n=133,136)	2	2
Heart: Week 16 (n=132, 132)	0	2
Heart: Week 48 (n=119, 119)	0	2
Lungs: Screening (n=133,136)	1	0
Lungs: Week 16 (n=132, 132)	0	0
Lungs: Week 48 (n=119, 119)	0	0
Lymph nodes: Screening (n=133, 136)	2	3
Lymph nodes: Week 16 (n=132, 131)	1	2
Lymph nodes: Week 48 (n=119, 119)	1	2
Neurological: Screening (n=133, 135)	4	0
Neurological: Week 16 (n=132, 131)	1	0
Neurological: Week 48 (n=119, 119)	2	0
Skin: Screening (n=133, 135)	18	18
Skin: Week 16 (n=132, 132)	14	13
Skin: Week 48 (n=119, 119)	12	12

No statistical analyses for this end point

Secondary: Number of Subjects With Electrocardiogram (ECG) Abnormalities

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End point title

Number of Subjects With Electrocardiogram (ECG) Abnormalities

End point description

Twelve-lead electrocardiograms (ECGs) were obtained for all subjects. Criteria for ECG abnormality: PR interval >=300 and a percent change from baseline of >=25 or 50%; QRS duration >=140 and a percent change from baseline of >=50%; QT interval >=500; QTCB, QTCF interval <480 or >=450, <500 or >=480, >=500, change from baseline of <60 and >=30, and change from baseline of >=60. Safety analysis set: included all subjects who were randomised and received at least one dose of the investigational product (i.e., tofacitinib or placebo). Here "number of subjects analysed" signifies subjects analysed for this end point and 'n' = subjects analysed for this end point for specified rows.

End point type

Secondary

End point timeframe

Baseline (BL) to Week 16 (W16), Baseline to Week 48 (W48)

End point values	Tofacitinib	Placebo Then Tofacitinib
Number of subjects analysed	131	133
Units: Subjects
BL to W16, PR interval: >=300, n=131,131	0	0
BL to W16, PR interval:%Change>=25/50%, n=131,131	0	1
BL to W16, QRS duration: >=140, n=131,131	1	1
BL to W16, QRS duration:%Change>=50%, n=131,131	0	0
BL to W16, QT interval: >=500, n=131,131	0	0
BL to W16, QTCB interval:>=450 and <480, n=131,131	3	7
BL to W16, QTCB interval:>=480 and <500, n=131,131	0	1
BL to W16, QTCB interval: >=500, n=131,131	0	0
BL to W16, QTCB interval:change >=30,<60,n=131,131	9	7
BL to W16, QTCB interval: change >=60, n=131,131	0	0
BL to W16, QTCF interval:>=450 and <480,n=131,131	3	4
BL to W16, QTCF interval:>=480 and <500,n=131,131	0	0
BL to W16, QTCF interval: >=500, n=131,131	0	0
BL to W16, QTCF interval:change >=30,<60,n=131,131	5	3
BL to W16, QTCF interval: change >=60,n=131,131	0	0
BL to W48, PR interval: >=300, n=131,133	0	0
BL to W48, PR interval:%Change>=25/50%, n=131,133	0	1
BL to W48, QRS duration: >=140, n=131,133	3	1
BL to W48, QRS duration: %Change>=50%, n=131,133	0	0
BL to W48, QT interval: >=500, n=131,133	0	1
BL to W48, QTCB interval:>=450, <480,n=131,133	10	10
BL to W48, QTCB interval:>=480,<500,n=131,133	1	1
BL to W48, QTCB interval: >=500, n=131,133	0	0
BL to W48, QTCB interval:change >=30,<60,n=131,133	14	11
BL to W48, QTCB interval: change >=60,n=131,133	1	0
BL to W48, QTCF interval:>=450,<480,n=131,133	5	5
BL to W48, QTCF interval:>=480,<500,n=131,133	1	0
BL to W48, QTCF interval: >=500, n=131,133	0	0
BL to W48, QTCF interval:change >=30,<60,n=131,133	9	7
BL to W48, QTCF interval: change >=60, n=131,133	1	0

No statistical analyses for this end point

Secondary: Percentage of Subjects Achieving ASAS20 Response at Weeks 2, 4, 8, 12, 24, 32, 40 and 48

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End point title

Percentage of Subjects Achieving ASAS20 Response at Weeks 2, 4, 8, 12, 24, 32, 40 and 48

End point description

ASAS20 assess 4 domains:PGA (assess disease activity on a scale of 0[not active] to 10[very active], high score=more disease activity), total back pain (scale of 0[no pain] to 10[most severe pain], high score=more severity), Function (BASFI; subject’s level of ability on scale of 0[easy] to 10[impossible], low score= better functional health), Inflammation (morning stiffness, Mean of Q5 and Q6 of BASDAI defined as 6-item questionnaire measure disease activity on a scale of 0[none] to 10[severe], high score=more disease activity). ASAS20 response: >=20% improvement from baseline in disease activity, absolute change of >=1 unit in >=3 domains, no worsening of >=20%, an absolute change of >=1 unit in remaining domain. FAS: included all subject who were randomised to study, received at least one dose of randomised investigational product. Here, on-drug data was used, MR=NR.

End point type

Secondary

End point timeframe

Weeks 2, 4, 8, 12, 24, 32, 40 and 48

End point values	Tofacitinib	Placebo Then Tofacitinib
Number of subjects analysed	133	136
Units: Percentage of subjects
number (not applicable)
Week 2	28.57	10.29
Week 4	51.13	19.85
Week 8	57.14	25.00
Week 12	63.91	29.41
Week 24	63.16	59.56
Week 32	68.42	64.71
Week 40	68.42	66.91
Week 48	65.41	60.29

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 2: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

269

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0001

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

18.28

Confidence interval

level

95%

sides

2-sided

lower limit

9.06

upper limit

27.5

Variability estimate

Standard error of the mean

Dispersion value

4.7

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 4: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

269

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

31.35

Confidence interval

level

95%

sides

2-sided

lower limit

20.64

upper limit

42.06

Variability estimate

Standard error of the mean

Dispersion value

5.47

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 8: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

269

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

32.24

Confidence interval

level

95%

sides

2-sided

lower limit

21.32

upper limit

43.17

Variability estimate

Standard error of the mean

Dispersion value

5.57

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 12: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

269

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

34.61

Confidence interval

level

95%

sides

2-sided

lower limit

23.63

upper limit

45.58

Variability estimate

Standard error of the mean

Dispersion value

5.6

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 40: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

269

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7792

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

1.58

Confidence interval

level

95%

sides

2-sided

lower limit

-9.49

upper limit

12.66

Variability estimate

Standard error of the mean

Dispersion value

5.65

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 48: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

269

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3685

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

5.22

Confidence interval

level

95%

sides

2-sided

lower limit

-6.15

upper limit

16.58

Variability estimate

Standard error of the mean

Dispersion value

5.8

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 24: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

269

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.536

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

3.65

Confidence interval

level

95%

sides

2-sided

lower limit

-7.92

upper limit

15.22

Variability estimate

Standard error of the mean

Dispersion value

5.9

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 32: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

269

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4971

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

3.83

Confidence interval

level

95%

sides

2-sided

lower limit

-7.22

upper limit

14.87

Variability estimate

Standard error of the mean

Dispersion value

5.63

Secondary: Percentage of Subjects Achieving ASAS40 Response at Weeks 2, 4, 8, 12, 24, 32, 40 and 48

Top of page

End point title

Percentage of Subjects Achieving ASAS40 Response at Weeks 2, 4, 8, 12, 24, 32, 40 and 48

End point description

ASAS40 assessed 4 domains: “PGA” (assess disease activity on a scale of 0 [not active] to 10 [very active], high score=more disease activity), total back pain (on a scale of 0 [no pain] to 10 [most severe pain], high score=more severity), Function (from BASFI: assess subject’s level of ability on a scale of 0 [easy] to 10 [impossible], low score= better functional health), Inflammation (morning stiffness, Mean of Q5 and Q6 of BASDAI defined as 6 item questionnaire: measure disease activity on a scale of 0 [none] to 10 [severe], high score=more disease activity). ASAS40 response: >=40% and >=2 units improvement in >=3 domains, no worsening at all in the remaining domain. FAS: include all subjects who were randomised to the study, received at least one dose of randomised investigational product (i.e., tofacitinib or placebo). On-drug data was used, MR=NR.

End point type

Secondary

End point timeframe

Weeks 2, 4, 8, 12, 24, 32, 40 and 48

End point values	Tofacitinib	Placebo Then Tofacitinib
Number of subjects analysed	133	136
Units: Percentage of subjects
number (not applicable)
Week 2	10.53	4.41
Week 4	27.07	3.68
Week 8	34.59	5.88
Week 12	42.86	11.76
Week 24	48.12	41.91
Week 32	50.38	44.12
Week 40	50.38	42.65
Week 48	50.38	44.85

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 2: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

269

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0548

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

6.12

Confidence interval

level

95%

sides

2-sided

lower limit

-0.13

upper limit

12.37

Variability estimate

Standard error of the mean

Dispersion value

3.19

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 4: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

269

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

23.43

Confidence interval

level

95%

sides

2-sided

lower limit

15.3

upper limit

31.56

Variability estimate

Standard error of the mean

Dispersion value

4.15

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 8: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

269

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

28.56

Confidence interval

level

95%

sides

2-sided

lower limit

19.66

upper limit

37.47

Variability estimate

Standard error of the mean

Dispersion value

4.54

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 12: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

269

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

31.18

Confidence interval

level

95%

sides

2-sided

lower limit

21.34

upper limit

41.02

Variability estimate

Standard error of the mean

Dispersion value

5.02

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 24: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

269

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2926

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

6.29

Confidence interval

level

95%

sides

2-sided

lower limit

-5.43

upper limit

18.01

Variability estimate

Standard error of the mean

Dispersion value

5.98

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 32: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

269

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2856

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

6.37

Confidence interval

level

95%

sides

2-sided

lower limit

-5.32

upper limit

18.06

Variability estimate

Standard error of the mean

Dispersion value

5.97

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 40: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

269

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1894

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

7.83

Confidence interval

level

95%

sides

2-sided

lower limit

-3.87

upper limit

19.54

Variability estimate

Standard error of the mean

Dispersion value

5.97

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 48: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

269

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3544

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

5.59

Confidence interval

level

95%

sides

2-sided

lower limit

-6.24

upper limit

17.43

Variability estimate

Standard error of the mean

Dispersion value

6.04

Secondary: Change From Baseline in Ankylosing Spondylitis Disease Activity Score using C-Reactive Protein (ASDAS[CRP]) at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Top of page

End point title

Change From Baseline in Ankylosing Spondylitis Disease Activity Score using C-Reactive Protein (ASDAS[CRP]) at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

End point description

ASDAS(CRP) derived using BASDAI (6-item questionnaire measure disease activity:scale 0[none] to 10[severe],high score=more disease activity),PGA:measure disease activity:scale 0 [not active] to 10 [very active],high score=more disease activity),calculated by using formula,0.121xBack Pain(Q2 of BASDAI)+0.058xDuration of Morning Stiffness(Q6 of BASDAI)+0.110xPGA+0.073xPeripheral Pain/Swelling(Q3 of BASDAI)+0.579xLn (high sensitivity [hs] CRP mg/Liter[L]+1).If hsCRP values smaller than 2mg/L,they were set to 2mg/L in formula.Range of score >=0.636 to no defined upper limit.Negative change from baseline value=decrease in disease activity;positive change from baseline value=increase in disease activity.FAS:all subject randomised to study,received >=1 of investigational product.On-drug data used,missing response not imputed."number of subject analysed"=subject analysed for end point.

End point type

Secondary

End point timeframe

Baseline, Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

End point values	Tofacitinib	Placebo Then Tofacitinib
Number of subjects analysed	132	136
Units: Units on a scale
least squares mean (standard error)
Week 2	-0.88 ( 0.056 )	-0.17 ( 0.056 )
Week 4	-1.14 ( 0.065 )	-0.24 ( 0.065 )
Week 8	-1.30 ( 0.074 )	-0.24 ( 0.074 )
Week 12	-1.38 ( 0.075 )	-0.28 ( 0.075 )
Week 16	-1.36 ( 0.073 )	-0.39 ( 0.073 )
Week 24	-1.51 ( 0.082 )	-1.32 ( 0.081 )
Week 32	-1.56 ( 0.084 )	-1.37 ( 0.084 )
Week 40	-1.65 ( 0.086 )	-1.40 ( 0.086 )
Week 48	-1.70 ( 0.087 )	-1.50 ( 0.086 )

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 2: Analysis performed using Mixed model for repeated measures (MMRM) which included fixed effect of treatment group, visit, and treatment-group by visit interaction, stratification factor derived from clinical database, stratification-factor by visit interaction, baseline value, and baseline-value by visit interaction.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.71

Confidence interval

level

95%

sides

2-sided

lower limit

-0.85

upper limit

-0.57

Variability estimate

Standard error of the mean

Dispersion value

0.072

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 4: Analysis performed using MMRM which included fixed effect of treatment group, visit, and treatment-group by visit interaction, stratification factor derived from clinical database, stratification-factor by visit interaction, baseline value, and baseline-value by visit interaction.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.9

Confidence interval

level

95%

sides

2-sided

lower limit

-1.07

upper limit

-0.74

Variability estimate

Standard error of the mean

Dispersion value

0.083

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 8: Analysis performed using MMRM which included fixed effect of treatment group, visit, and treatment-group by visit interaction, stratification factor derived from clinical database, stratification-factor by visit interaction, baseline value, and baseline-value by visit interaction.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-1.06

Confidence interval

level

95%

sides

2-sided

lower limit

-1.25

upper limit

-0.87

Variability estimate

Standard error of the mean

Dispersion value

0.095

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 12: Analysis performed using MMRM which included fixed effect of treatment group, visit, and treatment-group by visit interaction, stratification factor derived from clinical database, stratification-factor by visit interaction, baseline value, and baseline-value by visit interaction.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-1.09

Confidence interval

level

95%

sides

2-sided

lower limit

-1.28

upper limit

-0.9

Variability estimate

Standard error of the mean

Dispersion value

0.096

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 16: Analysis performed using MMRM which included fixed effect of treatment group, visit, and treatment-group by visit interaction, stratification factor derived from clinical database, stratification-factor by visit interaction, baseline value, and baseline-value by visit interaction.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.98

Confidence interval

level

95%

sides

2-sided

lower limit

-1.16

upper limit

-0.79

Variability estimate

Standard error of the mean

Dispersion value

0.093

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 24: Analysis performed using Mixed model for repeated measures (MMRM) which included fixed effect of treatment group, visit, and treatment-group by visit interaction, stratification factor derived from clinical database, stratification-factor by visit interaction, baseline value, and baseline-value by visit interaction.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0623

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.19

Confidence interval

level

95%

sides

2-sided

lower limit

-0.4

upper limit

0.01

Variability estimate

Standard error of the mean

Dispersion value

0.103

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 32: Analysis performed using Mixed model for repeated measures (MMRM) which included fixed effect of treatment group, visit, and treatment-group by visit interaction, stratification factor derived from clinical database, stratification-factor by visit interaction, baseline value, and baseline-value by visit interaction.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0836

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.18

Confidence interval

level

95%

sides

2-sided

lower limit

-0.39

upper limit

0.02

Variability estimate

Standard error of the mean

Dispersion value

0.106

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 40: Analysis performed using Mixed model for repeated measures (MMRM) which included fixed effect of treatment group, visit, and treatment-group by visit interaction, stratification factor derived from clinical database, stratification-factor by visit interaction, baseline value, and baseline-value by visit interaction.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0205

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.25

Confidence interval

level

95%

sides

2-sided

lower limit

-0.47

upper limit

-0.04

Variability estimate

Standard error of the mean

Dispersion value

0.108

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 48: Analysis performed using Mixed model for repeated measures (MMRM) which included fixed effect of treatment group, visit, and treatment-group by visit interaction, stratification factor derived from clinical database, stratification-factor by visit interaction, baseline value, and baseline-value by visit interaction.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0614

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.42

upper limit

0.01

Variability estimate

Standard error of the mean

Dispersion value

0.108

Secondary: Change From Baseline in High Sensitivity C-Reactive Protein (hsCRP) at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Top of page

End point title

Change From Baseline in High Sensitivity C-Reactive Protein (hsCRP) at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

End point description

Blood samples were collected for analysis of hsCRP using an assay analyzed by central laboratory. hsCRP is an acute phase reactant, which was indicative of inflammation and of its severity. FAS: included all subjects who were randomised to the study and received at least one dose of the randomised investigational product (i.e., tofacitinib or placebo). Here, on-drug data was used and missing response was not imputed. Here "number of subjects analysed" signifies subjects analysed for this end point.

End point type

Secondary

End point timeframe

Baseline, Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

End point values	Tofacitinib	Placebo Then Tofacitinib
Number of subjects analysed	132	136
Units: Milligrams per decilitre (mg/dL)
least squares mean (standard error)
Week 2	-1.07 ( 0.089 )	-0.14 ( 0.088 )
Week 4	-1.06 ( 0.094 )	-0.14 ( 0.094 )
Week 8	-1.05 ( 0.153 )	-0.03 ( 0.152 )
Week 12	-1.11 ( 0.089 )	-0.15 ( 0.090 )
Week 16	-1.05 ( 0.096 )	-0.09 ( 0.096 )
Week 24	-1.21 ( 0.058 )	-1.16 ( 0.058 )
Week 32	-1.16 ( 0.076 )	-1.08 ( 0.075 )
Week 40	-1.22 ( 0.089 )	-1.09 ( 0.089 )
Week 48	-1.17 ( 0.081 )	-1.11 ( 0.080 )

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 2: Analysis performed using MMRM which included fixed effect of treatment group, visit, and treatment-group by visit interaction, stratification factor derived from clinical database, stratification-factor by visit interaction, baseline value, and baseline-value by visit interaction.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.93

Confidence interval

level

95%

sides

2-sided

lower limit

-1.15

upper limit

-0.7

Variability estimate

Standard error of the mean

Dispersion value

0.113

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.92

Confidence interval

level

95%

sides

2-sided

lower limit

-1.16

upper limit

-0.68

Variability estimate

Standard error of the mean

Dispersion value

0.121

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-1.02

Confidence interval

level

95%

sides

2-sided

lower limit

-1.4

upper limit

-0.63

Variability estimate

Standard error of the mean

Dispersion value

0.196

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.96

Confidence interval

level

95%

sides

2-sided

lower limit

-1.19

upper limit

-0.74

Variability estimate

Standard error of the mean

Dispersion value

0.115

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.96

Confidence interval

level

95%

sides

2-sided

lower limit

-1.2

upper limit

-0.72

Variability estimate

Standard error of the mean

Dispersion value

0.122

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 24: Analysis performed using MMRM which included fixed effect of treatment group, visit, and treatment-group by visit interaction, stratification factor derived from clinical database, stratification-factor by visit interaction, baseline value, and baseline-value by visit interaction.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4731

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.05

Confidence interval

level

95%

sides

2-sided

lower limit

-0.2

upper limit

0.09

Variability estimate

Standard error of the mean

Dispersion value

0.073

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 32: Analysis performed using MMRM which included fixed effect of treatment group, visit, and treatment-group by visit interaction, stratification factor derived from clinical database, stratification-factor by visit interaction, baseline value, and baseline-value by visit interaction.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4055

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.08

Confidence interval

level

95%

sides

2-sided

lower limit

-0.26

upper limit

0.11

Variability estimate

Standard error of the mean

Dispersion value

0.094

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 40: Analysis performed using MMRM which included fixed effect of treatment group, visit, and treatment-group by visit interaction, stratification factor derived from clinical database, stratification-factor by visit interaction, baseline value, and baseline-value by visit interaction.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2648

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.12

Confidence interval

level

95%

sides

2-sided

lower limit

-0.34

upper limit

0.09

Variability estimate

Standard error of the mean

Dispersion value

0.111

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 48: Analysis performed using MMRM which included fixed effect of treatment group, visit, and treatment-group by visit interaction, stratification factor derived from clinical database, stratification-factor by visit interaction, baseline value, and baseline-value by visit interaction.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5558

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.06

Confidence interval

level

95%

sides

2-sided

lower limit

-0.25

upper limit

0.14

Variability estimate

Standard error of the mean

Dispersion value

0.099

Secondary: Change From Baseline in Ankylosing Spondylitis Quality of Life (ASQoL) Score at Weeks 16 and 48

Top of page

End point title

Change From Baseline in Ankylosing Spondylitis Quality of Life (ASQoL) Score at Weeks 16 and 48

End point description

The ASQoL was an 18-item questionnaire assessed the amount of restriction subject experienced in daily activities, level of pain and fatigue, and the impact on the subject's emotional state. Each item was scored as 0 (no impact) or 1 (yes - impact). A total score was calculated by summing the items. The total score ranged from 0 (no impact) to 18 (yes-impact), with higher values indicated more impaired health-related quality of life. FAS: included all subjects who were randomised to the study and received at least one dose of the randomised investigational product (i.e., tofacitinib or placebo). Here, on-drug data was used and missing response was not imputed. Here "number of subjects analysed" signifies subjects analysed for this end point and 'n'= subjects analysed for this end point for specified time points.

End point type

Secondary

End point timeframe

Baseline, Weeks 16 and 48

End point values	Tofacitinib	Placebo Then Tofacitinib
Number of subjects analysed	129	131
Units: Units on scale
least squares mean (standard error)
Week 16 (n=129,130)	-4.03 ( 0.404 )	-2.01 ( 0.405 )
Week 48 (n=129, 131)	-5.97 ( 0.454 )	-4.70 ( 0.451 )

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 16: Analysis performed using Analysis of covariance (ANCOVA) model which included fixed effects of treatment group, stratification factor derived from clinical database, and baseline value.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

260

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0001

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

-2.02

Confidence interval

level

95%

sides

2-sided

lower limit

-3.03

upper limit

-1.01

Variability estimate

Standard error of the mean

Dispersion value

0.513

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

260

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.027

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-1.26

Confidence interval

level

95%

sides

2-sided

lower limit

-2.38

upper limit

-0.14

Variability estimate

Standard error of the mean

Dispersion value

0.567

Secondary: Change From Baseline in Short-Form-36 Health Survey-Version 2 Acute (SF-36v2) Score at Weeks 16 and 48

Top of page

End point title

Change From Baseline in Short-Form-36 Health Survey-Version 2 Acute (SF-36v2) Score at Weeks 16 and 48

End point description

36-item health status measure,8 domain:physical functioning,role limitation-physical health,bodily pain,general health perception,vitality,social functioning,role limitation-emotional problem,mental health.Domain aggregate into 2 score-physical component summary(PCS),mental component summary(MCS).4 domain comprise PCS:physical functioning,role-physical,bodily pain,general health,remaining 4 domain comprise MCS:vitality,social functioning,role-emotional,mental health.Normalized domain,PCS,MCS score used in analyses.Component,domain score by using US 1998 general population norm.Resulting norm-based score for SF36 version 2,SF36 health domain scale,component summary measure had mean 50 and standard deviations 10.High PCS/MCS/domain score=better health status.FAS:include all subject who were randomised to study,received >=1 dose of investigational product (tofacitinib or placebo).On-drug data used,MR not imputed.Number of subject analysed signify subjects analysed for this end point.

End point type

Secondary

End point timeframe

Baseline, Weeks 16 and 48

End point values	Tofacitinib	Placebo Then Tofacitinib
Number of subjects analysed	129	130
Units: Units on a scale
least squares mean (standard error)
Week 16: Physical Functioning	5.52 ( 0.665 )	3.29 ( 0.665 )
Week 16: Role-Physical	6.13 ( 0.744 )	3.13 ( 0.745 )
Week 16: Bodily Pain	7.93 ( 0.710 )	3.47 ( 0.713 )
Week 16: General Health	5.00 ( 0.617 )	1.76 ( 0.618 )
Week 16: Vitality	5.34 ( 0.864 )	3.56 ( 0.869 )
Week 16: Social Functioning	5.45 ( 0.835 )	2.49 ( 0.837 )
Week 16: Role-Emotional	4.13 ( 1.020 )	2.05 ( 1.017 )
Week 16: Mental Health	3.57 ( 0.886 )	2.49 ( 0.888 )
Week 16: Physical Component Summary	6.69 ( 0.588 )	3.14 ( 0.590 )
Week 16: Mental Component Summary	3.45 ( 0.914 )	2.13 ( 0.915 )
Week 48: Physical Functioning	7.80 ( 0.775 )	6.94 ( 0.766 )
Week 48: Role-Physical	8.66 ( 0.870 )	7.29 ( 0.862 )
Week 48: Bodily Pain	11.67 ( 0.920 )	9.55 ( 0.912 )
Week 48: General Health	6.31 ( 0.777 )	5.10 ( 0.770 )
Week 48: Vitality	9.83 ( 0.997 )	9.28 ( 0.992 )
Week 48: Social Functioning	8.16 ( 0.923 )	6.77 ( 0.915 )
Week 48: Role-Emotional	7.17 ( 1.004 )	6.32 ( 0.989 )
Week 48: Mental Health	7.10 ( 0.960 )	6.45 ( 0.954 )
Week 48: Physical Component Summary	8.81 ( 0.720 )	7.39 ( 0.714 )
Week 48: Mental Component Summary	7.07 ( 0.926 )	6.35 ( 0.920 )

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 16, Physical Functioning: Analysis performed using ANCOVA model which included fixed effects of treatment group, stratification factor derived from clinical database, and baseline value.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0088

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

2.22

Confidence interval

level

95%

sides

2-sided

lower limit

0.56

upper limit

3.88

Variability estimate

Standard error of the mean

Dispersion value

0.841

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 16, Role-Physical: Analysis performed using ANCOVA model which included fixed effects of treatment group, stratification factor derived from clinical database, and baseline value.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0016

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

1.15

upper limit

4.85

Variability estimate

Standard error of the mean

Dispersion value

0.939

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 16, Bodily Pain: Analysis performed using ANCOVA model which included fixed effects of treatment group, stratification factor derived from clinical database, and baseline value.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

4.46

Confidence interval

level

95%

sides

2-sided

lower limit

2.69

upper limit

6.23

Variability estimate

Standard error of the mean

Dispersion value

0.9

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 16, General Health: Analysis performed using ANCOVA model which included fixed effects of treatment group, stratification factor derived from clinical database, and baseline value.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

3.24

Confidence interval

level

95%

sides

2-sided

lower limit

1.7

upper limit

4.78

Variability estimate

Standard error of the mean

Dispersion value

0.781

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 16, Vitality: Analysis performed using ANCOVA model which included fixed effects of treatment group, stratification factor derived from clinical database, and baseline value.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1065

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

1.78

Confidence interval

level

95%

sides

2-sided

lower limit

-0.38

upper limit

3.94

Variability estimate

Standard error of the mean

Dispersion value

1.098

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 16, Social Functioning: Analysis performed using ANCOVA model which included fixed effects of treatment group, stratification factor derived from clinical database, and baseline value.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0055

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

2.96

Confidence interval

level

95%

sides

2-sided

lower limit

0.88

upper limit

5.05

Variability estimate

Standard error of the mean

Dispersion value

1.059

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 16, Role-Emotional: Analysis performed using ANCOVA model which included fixed effects of treatment group, stratification factor derived from clinical database, and baseline value.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1084

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

2.08

Confidence interval

level

95%

sides

2-sided

lower limit

-0.46

upper limit

4.61

Variability estimate

Standard error of the mean

Dispersion value

1.289

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 16, Mental Health: Analysis performed using ANCOVA model which included fixed effects of treatment group, stratification factor derived from clinical database, and baseline value.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3379

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

1.08

Confidence interval

level

95%

sides

2-sided

lower limit

-1.13

upper limit

3.29

Variability estimate

Standard error of the mean

Dispersion value

1.124

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 16, Physical Component Summary: Analysis performed using ANCOVA model which included fixed effects of treatment group, stratification factor derived from clinical database, and baseline value.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

3.55

Confidence interval

level

95%

sides

2-sided

lower limit

2.09

upper limit

5.02

Variability estimate

Standard error of the mean

Dispersion value

0.744

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 16, Mental Component Summary: Analysis performed using ANCOVA model which included fixed effects of treatment group, stratification factor derived from clinical database, and baseline value.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2529

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

1.33

Confidence interval

level

95%

sides

2-sided

lower limit

-0.95

upper limit

3.61

Variability estimate

Standard error of the mean

Dispersion value

1.158

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 48, Physical Functioning: Analysis performed using MMRM which included fixed effect of treatment group, visit, and treatment-group by visit interaction, stratification factor derived from clinical database, stratification-factor by visit interaction, baseline value, and baseline-value by visit interaction.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3744

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

0.86

Confidence interval

level

95%

sides

2-sided

lower limit

-1.04

upper limit

2.76

Variability estimate

Standard error of the mean

Dispersion value

0.964

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 48, Role-Physical: Analysis performed using MMRM which included fixed effect of treatment group, visit, and treatment-group by visit interaction, stratification factor derived from clinical database, stratification-factor by visit interaction, baseline value, and baseline-value by visit interaction.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2091

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

1.36

Confidence interval

level

95%

sides

2-sided

lower limit

-0.77

upper limit

3.5

Variability estimate

Standard error of the mean

Dispersion value

1.083

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 48, Bodily Pain: Analysis performed using MMRM which included fixed effect of treatment group, visit, and treatment-group by visit interaction, stratification factor derived from clinical database, stratification-factor by visit interaction, baseline value, and baseline-value by visit interaction.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0654

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

2.12

Confidence interval

level

95%

sides

2-sided

lower limit

-0.14

upper limit

4.38

Variability estimate

Standard error of the mean

Dispersion value

1.146

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 48, General Health: Analysis performed using MMRM which included fixed effect of treatment group, visit, and treatment-group by visit interaction, stratification factor derived from clinical database, stratification-factor by visit interaction, baseline value, and baseline-value by visit interaction.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.21

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

1.22

Confidence interval

level

95%

sides

2-sided

lower limit

-0.69

upper limit

3.12

Variability estimate

Standard error of the mean

Dispersion value

0.968

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 48, Vitality: Analysis performed using MMRM which included fixed effect of treatment group, visit, and treatment-group by visit interaction, stratification factor derived from clinical database, stratification-factor by visit interaction, baseline value, and baseline-value by visit interaction.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.6568

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

0.56

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

3.01

Variability estimate

Standard error of the mean

Dispersion value

1.248

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 48, Social Functioning: Analysis performed using MMRM which included fixed effect of treatment group, visit, and treatment-group by visit interaction, stratification factor derived from clinical database, stratification-factor by visit interaction, baseline value, and baseline-value by visit interaction.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2288

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

1.39

Confidence interval

level

95%

sides

2-sided

lower limit

-0.88

upper limit

3.66

Variability estimate

Standard error of the mean

Dispersion value

1.152

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 48, Role-Emotional: Analysis performed using MMRM which included fixed effect of treatment group, visit, and treatment-group by visit interaction, stratification factor derived from clinical database, stratification-factor by visit interaction, baseline value, and baseline-value by visit interaction.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4955

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

0.85

Confidence interval

level

95%

sides

2-sided

lower limit

-1.61

upper limit

3.32

Variability estimate

Standard error of the mean

Dispersion value

1.25

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 48, Mental Health: Analysis performed using MMRM which included fixed effect of treatment group, visit, and treatment-group by visit interaction, stratification factor derived from clinical database, stratification-factor by visit interaction, baseline value, and baseline-value by visit interaction.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5888

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

0.65

Confidence interval

level

95%

sides

2-sided

lower limit

-1.71

upper limit

3.01

Variability estimate

Standard error of the mean

Dispersion value

1.2

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 48, Physical Component Summary: Analysis performed using MMRM which included fixed effect of treatment group, visit, and treatment-group by visit interaction, stratification factor derived from clinical database, stratification-factor by visit interaction, baseline value, and baseline-value by visit interaction.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.115

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

1.42

Confidence interval

level

95%

sides

2-sided

lower limit

-0.35

upper limit

3.18

Variability estimate

Standard error of the mean

Dispersion value

0.896

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 48, Mental Component Summary: Analysis performed using MMRM which included fixed effect of treatment group, visit, and treatment-group by visit interaction, stratification factor derived from clinical database, stratification-factor by visit interaction, baseline value, and baseline-value by visit interaction.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5347

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

0.72

Confidence interval

level

95%

sides

2-sided

lower limit

-1.56

upper limit

Variability estimate

Standard error of the mean

Dispersion value

1.158

Secondary: Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) Scores: Cervical Rotation Angle at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Top of page

End point title

Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) Scores: Cervical Rotation Angle at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

End point description

BASMI assess axial status,spinal mobility.Compose of 5 clinical measure:lateral spinal flexion,tragus-to-wall distance,lumbar flexion,maximal intermalleolar distance,cervical rotation.BASMI-Linear Method score average of 5 score map:0-10,high score=more impairment.Cervical rotation angle:subject sit straight on chair with chin level,hand on knee.Blind assessor place goniometer at top of head in line with nose,ask subject to rotate neck maximal to left,follow with goniometer,record angle between sagittal plane,new plane after rotation.2nd reading obtain,both reading record.Procedure repeat for right.Better of 2 select for scoring;done by calculate mean of left,right measurement,record in degree(0-90),high cervical rotation=better health.FAS:include subject randomise to study,receive >=1 dose.On-drug data use,MR not impute.Number of subjects analysed=subjects analysed for end point.

End point type

Secondary

End point timeframe

Baseline, Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

End point values	Tofacitinib	Placebo Then Tofacitinib
Number of subjects analysed	132	136
Units: Degrees
least squares mean (standard error)
Week 2	2.25 ( 0.701 )	0.95 ( 0.698 )
Week 4	3.63 ( 0.797 )	2.07 ( 0.792 )
Week 8	6.26 ( 0.825 )	2.44 ( 0.824 )
Week 12	6.24 ( 1.002 )	2.92 ( 1.004 )
Week 16	7.74 ( 1.009 )	3.00 ( 1.008 )
Week 24	7.68 ( 1.139 )	7.49 ( 1.131 )
Week 32	7.25 ( 1.087 )	8.23 ( 1.080 )
Week 40	7.62 ( 1.215 )	8.34 ( 1.207 )
Week 48	7.63 ( 1.201 )	8.23 ( 1.188 )

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1513

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

1.29

Confidence interval

level

95%

sides

2-sided

lower limit

-0.48

upper limit

3.06

Variability estimate

Standard error of the mean

Dispersion value

0.898

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1279

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

1.56

Confidence interval

level

95%

sides

2-sided

lower limit

-0.45

upper limit

3.56

Variability estimate

Standard error of the mean

Dispersion value

1.02

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0003

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

3.83

Confidence interval

level

95%

sides

2-sided

lower limit

1.75

upper limit

5.9

Variability estimate

Standard error of the mean

Dispersion value

1.056

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0102

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

3.32

Confidence interval

level

95%

sides

2-sided

lower limit

0.79

upper limit

5.84

Variability estimate

Standard error of the mean

Dispersion value

1.282

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0003

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

4.73

Confidence interval

level

95%

sides

2-sided

lower limit

2.2

upper limit

7.26

Variability estimate

Standard error of the mean

Dispersion value

1.285

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.895

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

0.19

Confidence interval

level

95%

sides

2-sided

lower limit

-2.64

upper limit

3.02

Variability estimate

Standard error of the mean

Dispersion value

1.439

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4732

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.98

Confidence interval

level

95%

sides

2-sided

lower limit

-3.67

upper limit

1.71

Variability estimate

Standard error of the mean

Dispersion value

1.365

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.6359

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.72

Confidence interval

level

95%

sides

2-sided

lower limit

-3.72

upper limit

2.28

Variability estimate

Standard error of the mean

Dispersion value

1.523

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.6894

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-3.54

upper limit

2.35

Variability estimate

Standard error of the mean

Dispersion value

1.495

Secondary: Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) Scores: Intermalleolar Distance at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Top of page

End point title

Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) Scores: Intermalleolar Distance at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

End point description

BASMI assess axial status, spinal mobility using linear function. It compose of 5 clinical measures:lateral spinal flexion, tragus-to-wall distance, lumbar flexion, maximal intermalleolar distance, cervical rotation. BASMI - Linear Method score average of 5 individual component scores mapped between 0-10, high score=more impairment. For assessment of intermalleolar distance, subjects lie supine with knees straight and feet/toes pointing straight up, asked to separate legs as far as possible, distance between medial malleoli measured (in Centimetres [cm] to nearest 0.1cm). Distance was>=0, with no maximum defined range: high intermalleolar distance value=better health status. FAS: include all subjects randomised to study, received at least one dose of investigational product. On-drug data used, MR not imputed. Number of subjects analysed=subjects analysed for this end point.

End point type

Secondary

End point timeframe

Baseline, Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

End point values	Tofacitinib	Placebo Then Tofacitinib
Number of subjects analysed	132	136
Units: Centimetres
least squares mean (standard error)
Week 2	2.29 ( 0.733 )	0.90 ( 0.730 )
Week 4	3.62 ( 0.861 )	0.84 ( 0.856 )
Week 8	4.68 ( 0.979 )	1.36 ( 0.976 )
Week 12	5.33 ( 1.106 )	1.97 ( 1.108 )
Week 16	6.84 ( 1.084 )	2.64 ( 1.082 )
Week 24	7.79 ( 1.177 )	4.39 ( 1.174 )
Week 32	8.98 ( 1.221 )	5.32 ( 1.215 )
Week 40	8.60 ( 1.229 )	4.75 ( 1.222 )
Week 48	7.83 ( 1.233 )	4.34 ( 1.222 )

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.141

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

1.39

Confidence interval

level

95%

sides

2-sided

lower limit

-0.46

upper limit

3.24

Variability estimate

Standard error of the mean

Dispersion value

0.94

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0122

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

2.78

Confidence interval

level

95%

sides

2-sided

lower limit

0.61

upper limit

4.95

Variability estimate

Standard error of the mean

Dispersion value

1.102

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0085

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

3.32

Confidence interval

level

95%

sides

2-sided

lower limit

0.86

upper limit

5.79

Variability estimate

Standard error of the mean

Dispersion value

1.252

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0184

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

3.36

Confidence interval

level

95%

sides

2-sided

lower limit

0.57

upper limit

6.15

Variability estimate

Standard error of the mean

Dispersion value

1.416

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0026

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

4.19

Confidence interval

level

95%

sides

2-sided

lower limit

1.47

upper limit

6.91

Variability estimate

Standard error of the mean

Dispersion value

1.38

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0236

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

3.4

Confidence interval

level

95%

sides

2-sided

lower limit

0.46

upper limit

6.35

Variability estimate

Standard error of the mean

Dispersion value

1.495

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0182

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

3.66

Confidence interval

level

95%

sides

2-sided

lower limit

0.63

upper limit

6.7

Variability estimate

Standard error of the mean

Dispersion value

1.541

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0133

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

3.85

Confidence interval

level

95%

sides

2-sided

lower limit

0.81

upper limit

6.9

Variability estimate

Standard error of the mean

Dispersion value

1.545

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0245

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

3.49

Confidence interval

level

95%

sides

2-sided

lower limit

0.45

upper limit

6.52

Variability estimate

Standard error of the mean

Dispersion value

1.541

Secondary: Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) Scores: Lateral Spinal Flexion at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Top of page

End point title

Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) Scores: Lateral Spinal Flexion at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

End point description

BASMI assess axial status,spinal mobility use linear function.Compose of 5 clinical measure.BASMI-Linear Method score:average of 5 component score map between 0-10,high score=more impairment.Assessment of lateral spinal flexion:subjects stand upright with head,back rest against wall as close as possible with shoulder level,feet 30cm apart,feet parallel.At tip of middle finger,place mark on thigh.This position record.Subjects bend sideway without bend knee/lifting heel while attempt to keep shoulder in same position.2nd mark placed,lateral flexion record.2 try left,2 try right measure.Result of 2 try recorded for left,right separately to nearest 0.1cm.Distance should be>=0,no maximum defined range:high value=better health status.FAS:include subject randomise to study,receive>=1dose of study drug.On-drug data use,MR not impute.Number of subject analysed=subject analysed for end point.

End point type

Secondary

End point timeframe

Baseline, Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

End point values	Tofacitinib	Placebo Then Tofacitinib
Number of subjects analysed	132	136
Units: Centimetres
least squares mean (standard error)
Week 2	0.60 ( 0.200 )	-0.21 ( 0.199 )
Week 4	0.96 ( 0.235 )	-0.10 ( 0.233 )
Week 8	1.34 ( 0.238 )	0.15 ( 0.237 )
Week 12	1.42 ( 0.214 )	-0.21 ( 0.214 )
Week 16	1.79 ( 0.269 )	-0.08 ( 0.269 )
Week 24	1.70 ( 0.278 )	0.75 ( 0.276 )
Week 32	1.90 ( 0.319 )	1.31 ( 0.316 )
Week 40	2.15 ( 0.332 )	1.37 ( 0.329 )
Week 48	1.64 ( 0.345 )	1.34 ( 0.340 )

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0018

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

0.81

Confidence interval

level

95%

sides

2-sided

lower limit

0.3

upper limit

1.32

Variability estimate

Standard error of the mean

Dispersion value

0.257

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0005

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

1.06

Confidence interval

level

95%

sides

2-sided

lower limit

0.47

upper limit

1.65

Variability estimate

Standard error of the mean

Dispersion value

0.301

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0001

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

1.19

Confidence interval

level

95%

sides

2-sided

lower limit

0.59

upper limit

1.79

Variability estimate

Standard error of the mean

Dispersion value

0.305

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

1.63

Confidence interval

level

95%

sides

2-sided

lower limit

1.09

upper limit

2.17

Variability estimate

Standard error of the mean

Dispersion value

0.274

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

1.87

Confidence interval

level

95%

sides

2-sided

lower limit

1.2

upper limit

2.55

Variability estimate

Standard error of the mean

Dispersion value

0.344

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0075

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

0.95

Confidence interval

level

95%

sides

2-sided

lower limit

0.26

upper limit

1.65

Variability estimate

Standard error of the mean

Dispersion value

0.353

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1489

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

0.58

Confidence interval

level

95%

sides

2-sided

lower limit

-0.21

upper limit

1.38

Variability estimate

Standard error of the mean

Dispersion value

0.403

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0609

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

0.78

Confidence interval

level

95%

sides

2-sided

lower limit

-0.04

upper limit

1.61

Variability estimate

Standard error of the mean

Dispersion value

0.417

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4822

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-0.54

upper limit

1.15

Variability estimate

Standard error of the mean

Dispersion value

0.429

Secondary: Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) Scores: Lumbar Flexion (Modified Schober) at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Top of page

End point title

Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) Scores: Lumbar Flexion (Modified Schober) at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

End point description

BASMI assess axial status, spinal mobility. BASMI Linear Method score average of 5 individual component score map between 0-10, high score=more impairment. Assessment of lumbar flexion: with subject standing erect, outer edge of feet 30cm apart, mark place in midpoint of line that join posterior superior iliac spines (baseline mark). 2nd mark (A) placed 10cm above baseline mark, 3rd mark (B) 5 cm below baseline mark. Then have subject maximally bend forward, keep knees fully extend. With subject’s spine in full flexion, distance between mark A,B (in cm to nearest 0.1cm) was re-measure. Distance was>=0, with no maximum defined range. High value=better health status. FAS: include all subjects who were randomised to study,receive at least one dose of randomised investigational product. On-drug data use, MR not impute. Number of subject analysed=subjects analysed for this end point.

End point type

Secondary

End point timeframe

Baseline, Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

End point values	Tofacitinib	Placebo Then Tofacitinib
Number of subjects analysed	132	136
Units: Centimetres
least squares mean (standard error)
Week 2	0.30 ( 0.102 )	-0.07 ( 0.102 )
Week 4	0.41 ( 0.102 )	-0.11 ( 0.102 )
Week 8	0.32 ( 0.116 )	-0.17 ( 0.115 )
Week 12	0.26 ( 0.111 )	-0.22 ( 0.111 )
Week 16	0.46 ( 0.115 )	-0.06 ( 0.115 )
Week 24	0.51 ( 0.149 )	0.20 ( 0.148 )
Week 32	0.64 ( 0.143 )	0.39 ( 0.142 )
Week 40	0.58 ( 0.156 )	0.50 ( 0.155 )
Week 48	0.45 ( 0.146 )	0.35 ( 0.144 )

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0047

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

0.37

Confidence interval

level

95%

sides

2-sided

lower limit

0.12

upper limit

0.63

Variability estimate

Standard error of the mean

Dispersion value

0.131

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0001

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

0.52

Confidence interval

level

95%

sides

2-sided

lower limit

0.26

upper limit

0.77

Variability estimate

Standard error of the mean

Dispersion value

0.131

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0012

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

0.49

Confidence interval

level

95%

sides

2-sided

lower limit

0.19

upper limit

0.78

Variability estimate

Standard error of the mean

Dispersion value

0.148

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0008

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

0.48

Confidence interval

level

95%

sides

2-sided

lower limit

0.2

upper limit

0.76

Variability estimate

Standard error of the mean

Dispersion value

0.142

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0004

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

0.53

Confidence interval

level

95%

sides

2-sided

lower limit

0.24

upper limit

0.81

Variability estimate

Standard error of the mean

Dispersion value

0.147

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0918

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

0.32

Confidence interval

level

95%

sides

2-sided

lower limit

-0.05

upper limit

0.69

Variability estimate

Standard error of the mean

Dispersion value

0.188

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.16

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

0.25

Confidence interval

level

95%

sides

2-sided

lower limit

-0.1

upper limit

0.61

Variability estimate

Standard error of the mean

Dispersion value

0.179

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.6776

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

0.08

Confidence interval

level

95%

sides

2-sided

lower limit

-0.3

upper limit

0.47

Variability estimate

Standard error of the mean

Dispersion value

0.195

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5646

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.25

upper limit

0.46

Variability estimate

Standard error of the mean

Dispersion value

0.18

Secondary: Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) Scores: Tragus-to-wall Distance at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Top of page

End point title

Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) Scores: Tragus-to-wall Distance at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

End point description

BASMI assess axial status,spinal mobility using linear function.Compose of 5 clinical measure:lateral spinal flexion,tragus-to-wall distance,lumbar flexion,maximal intermalleolar distance,cervical rotation.BASMI-Linear Method score average of 5 individual component score map between 0-10,high score=more impairment.Assessment of tragus-to-wall distance:subject place standing with his/her back against wall;knee straight;scapulae,buttock,heel against wall;head in as neutral position as possible.Distance between tragus,wall in cm measure to nearest 0.1cm from both right side,left side at maximum effort to touch head against wall.Distance should be >=0cm with no defined maximum value,low tragus-to-wall value=better health status.FAS:include all subject randomise, received >=1 dose of study drug.On-drug data use,MR not impute.Number of subject analysed= subject analysed for end point.

End point type

Secondary

End point timeframe

Baseline, Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

End point values	Tofacitinib	Placebo Then Tofacitinib
Number of subjects analysed	132	136
Units: Centimetres
least squares mean (standard error)
Week 2	-0.19 ( 0.126 )	-0.24 ( 0.125 )
Week 4	-0.48 ( 0.144 )	-0.07 ( 0.143 )
Week 8	-0.51 ( 0.177 )	0.36 ( 0.177 )
Week 12	-0.40 ( 0.169 )	0.23 ( 0.169 )
Week 16	-0.50 ( 0.168 )	0.09 ( 0.168 )
Week 24	-0.66 ( 0.202 )	-0.03 ( 0.201 )
Week 32	-0.66 ( 0.179 )	0.00 ( 0.178 )
Week 40	-0.60 ( 0.200 )	-0.14 ( 0.199 )
Week 48	-0.73 ( 0.204 )	-0.18 ( 0.202 )

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7291

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

0.06

Confidence interval

level

95%

sides

2-sided

lower limit

-0.26

upper limit

0.37

Variability estimate

Standard error of the mean

Dispersion value

0.161

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0257

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.41

Confidence interval

level

95%

sides

2-sided

lower limit

-0.78

upper limit

-0.05

Variability estimate

Standard error of the mean

Dispersion value

0.184

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0002

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.86

Confidence interval

level

95%

sides

2-sided

lower limit

-1.31

upper limit

-0.42

Variability estimate

Standard error of the mean

Dispersion value

0.227

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0041

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.63

Confidence interval

level

95%

sides

2-sided

lower limit

-1.05

upper limit

-0.2

Variability estimate

Standard error of the mean

Dispersion value

0.216

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0062

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.59

Confidence interval

level

95%

sides

2-sided

lower limit

-1.02

upper limit

-0.17

Variability estimate

Standard error of the mean

Dispersion value

0.215

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.014

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.63

Confidence interval

level

95%

sides

2-sided

lower limit

-1.13

upper limit

-0.13

Variability estimate

Standard error of the mean

Dispersion value

0.255

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0035

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.66

Confidence interval

level

95%

sides

2-sided

lower limit

-1.11

upper limit

-0.22

Variability estimate

Standard error of the mean

Dispersion value

0.225

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0645

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.47

Confidence interval

level

95%

sides

2-sided

lower limit

-0.97

upper limit

0.03

Variability estimate

Standard error of the mean

Dispersion value

0.253

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0341

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.54

Confidence interval

level

95%

sides

2-sided

lower limit

-1.05

upper limit

-0.04

Variability estimate

Standard error of the mean

Dispersion value

0.255

Secondary: Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) Linear Method Total Score at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Top of page

End point title

Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) Linear Method Total Score at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

End point description

BASMI used to assess axial status and spinal mobility (cervical, dorsal and lumbar spine, hips and pelvic soft tissue), was analyzed using linear function method. BASMI score composed of five clinical measures: lateral spinal flexion, tragus-to-wall distance, lumbar flexion (modified Schober), maximal intermalleolar distance,cervical rotation. BASMI - Linear Method score was average of 5 individual component scores mapped between 0 and 10, BASMI - Linear Method total score ranged from 0 (very good) to 10 (very poor), higher scores=more impairment of axial status and spinal mobility; lower scores=better health status. FAS: included all subjects who were randomised to study, received at least one dose of randomised investigational product. On-drug data was used, missing response was not imputed. Here "number of subjects analysed"=subjects analysed for this end point.

End point type

Secondary

End point timeframe

Baseline, Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

End point values	Tofacitinib	Placebo Then Tofacitinib
Number of subjects analysed	132	136
Units: Units on a scale
least squares mean (standard error)
Week 2	-0.25 ( 0.044 )	-0.03 ( 0.043 )
Week 4	-0.39 ( 0.053 )	-0.06 ( 0.053 )
Week 8	-0.49 ( 0.059 )	-0.03 ( 0.058 )
Week 12	-0.49 ( 0.058 )	-0.02 ( 0.058 )
Week 16	-0.63 ( 0.060 )	-0.11 ( 0.060 )
Week 24	-0.67 ( 0.068 )	-0.38 ( 0.068 )
Week 32	-0.74 ( 0.069 )	-0.52 ( 0.068 )
Week 40	-0.74 ( 0.074 )	-0.55 ( 0.073 )
Week 48	-0.69 ( 0.074 )	-0.54 ( 0.073 )

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0001

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.22

Confidence interval

level

95%

sides

2-sided

lower limit

-0.33

upper limit

-0.11

Variability estimate

Standard error of the mean

Dispersion value

0.056

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.33

Confidence interval

level

95%

sides

2-sided

lower limit

-0.47

upper limit

-0.2

Variability estimate

Standard error of the mean

Dispersion value

0.068

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.46

Confidence interval

level

95%

sides

2-sided

lower limit

-0.61

upper limit

-0.31

Variability estimate

Standard error of the mean

Dispersion value

0.075

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.47

Confidence interval

level

95%

sides

2-sided

lower limit

-0.62

upper limit

-0.32

Variability estimate

Standard error of the mean

Dispersion value

0.075

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.52

Confidence interval

level

95%

sides

2-sided

lower limit

-0.67

upper limit

-0.37

Variability estimate

Standard error of the mean

Dispersion value

0.077

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0008

Method

LS mean difference

Parameter type

LS mean difference

Point estimate

-0.29

Confidence interval

level

95%

sides

2-sided

lower limit

-0.46

upper limit

-0.12

Variability estimate

Standard error of the mean

Dispersion value

0.086

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0116

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.22

Confidence interval

level

95%

sides

2-sided

lower limit

-0.39

upper limit

-0.05

Variability estimate

Standard error of the mean

Dispersion value

0.086

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0416

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.19

Confidence interval

level

95%

sides

2-sided

lower limit

-0.37

upper limit

-0.01

Variability estimate

Standard error of the mean

Dispersion value

0.093

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0915

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.16

Confidence interval

level

95%

sides

2-sided

lower limit

-0.34

upper limit

0.03

Variability estimate

Standard error of the mean

Dispersion value

0.092

Secondary: Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Total Scores at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Top of page

End point title

Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Total Scores at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

End point description

FACIT-F:13-item questionnaire(felt fatigue,felt weak all over,felt listless,felt tired,had energy,had trouble starting things as tired,had trouble finishing things as tired,was able to do usual activities,need to sleep during day,too tired to eat,need help doing usual activities,frustrated by being too tired to do things want to do,had to limit social activity because tired),each item score on 5-point scale:0 (not at all)to 4(very much).3 type of score derive:change in FACIT-F total score,change in FACIT-F experience domain score,change in FACIT-F impact domain score.FACIT-F total score calculate:summing 13 item(range 0[not at all] to 52[very much]);high score=less fatigue status.Here, change from baseline in FACIT-F total score report.FAS:all subject randomise, receive>= 1dose of study drug.On-drug data use,MR not imputed.Number of subject analysed=subject analysed for end point.

End point type

Secondary

End point timeframe

Baseline, Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

End point values	Tofacitinib	Placebo Then Tofacitinib
Number of subjects analysed	132	136
Units: Units on a scale
least squares mean (standard error)
Week 2	3.16 ( 0.552 )	0.32 ( 0.548 )
Week 4	4.80 ( 0.595 )	1.19 ( 0.591 )
Week 8	6.46 ( 0.706 )	1.03 ( 0.703 )
Week 12	6.25 ( 0.737 )	1.24 ( 0.736 )
Week 16	6.54 ( 0.795 )	3.12 ( 0.794 )
Week 24	7.42 ( 0.842 )	5.84 ( 0.836 )
Week 32	7.90 ( 0.813 )	7.24 ( 0.807 )
Week 40	8.67 ( 0.817 )	7.15 ( 0.810 )
Week 48	9.54 ( 0.897 )	7.35 ( 0.891 )

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

2.85

Confidence interval

level

95%

sides

2-sided

lower limit

1.46

upper limit

4.24

Variability estimate

Standard error of the mean

Dispersion value

0.706

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

3.61

Confidence interval

level

95%

sides

2-sided

lower limit

2.11

upper limit

5.1

Variability estimate

Standard error of the mean

Dispersion value

0.761

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

5.42

Confidence interval

level

95%

sides

2-sided

lower limit

3.65

upper limit

7.2

Variability estimate

Standard error of the mean

Dispersion value

0.902

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

5.01

Confidence interval

level

95%

sides

2-sided

lower limit

3.15

upper limit

6.86

Variability estimate

Standard error of the mean

Dispersion value

0.943

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0008

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

3.43

Confidence interval

level

95%

sides

2-sided

lower limit

1.44

upper limit

5.42

Variability estimate

Standard error of the mean

Dispersion value

1.012

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.139

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

1.58

Confidence interval

level

95%

sides

2-sided

lower limit

-0.52

upper limit

3.68

Variability estimate

Standard error of the mean

Dispersion value

1.064

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5217

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

0.66

Confidence interval

level

95%

sides

2-sided

lower limit

-1.36

upper limit

2.67

Variability estimate

Standard error of the mean

Dispersion value

1.024

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1415

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

1.51

Confidence interval

level

95%

sides

2-sided

lower limit

-0.51

upper limit

3.54

Variability estimate

Standard error of the mean

Dispersion value

1.027

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0533

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

2.19

Confidence interval

level

95%

sides

2-sided

lower limit

-0.03

upper limit

4.41

Variability estimate

Standard error of the mean

Dispersion value

1.128

Secondary: Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Experience Domain Scores at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Top of page

End point title

Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Experience Domain Scores at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

End point description

13-item(felt fatigue,felt weak all over,felt listless,felt tired,had energy,had trouble starting thing as tired,had trouble finishing thing as tired,was able to do usual activity,need to sleep during day,too tired to eat,need help doing usual activity,frustrate by being too tired to do thing wanted to do,had to limit social activity because tired) questionnaire,each item score on 5-point scale:0(not at all)to 4(very much).FACIT-F experience domain score calculate:summing 5 item:feel fatigued,feel weak all over,feel listless,feel tired,have energy.FACIT-F total experience domain score:0(not at all)to 20(very much),high score=less fatigue impact on daily function.Here,change from baseline in FACIT-F experience domain score report.FAS:include all subject randomise,receive>=1 dose of study drug.On-drug data use,MR not impute.Number of subjects analysed=subject analysed for end point.

End point type

Secondary

End point timeframe

Baseline, Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

End point values	Tofacitinib	Placebo Then Tofacitinib
Number of subjects analysed	132	136
Units: Units on a scale
least squares mean (standard error)
Week 2	1.35 ( 0.275 )	0.11 ( 0.274 )
Week 4	2.30 ( 0.298 )	0.60 ( 0.296 )
Week 8	2.72 ( 0.331 )	0.53 ( 0.330 )
Week 12	2.78 ( 0.343 )	0.80 ( 0.344 )
Week 16	2.85 ( 0.357 )	1.29 ( 0.357 )
Week 24	3.58 ( 0.384 )	2.96 ( 0.382 )
Week 32	3.65 ( 0.370 )	3.43 ( 0.367 )
Week 40	3.98 ( 0.375 )	3.59 ( 0.371 )
Week 48	4.22 ( 0.403 )	3.40 ( 0.400 )

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0005

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

1.25

Confidence interval

level

95%

sides

2-sided

lower limit

0.55

upper limit

1.94

Variability estimate

Standard error of the mean

Dispersion value

0.352

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

1.7

Confidence interval

level

95%

sides

2-sided

lower limit

0.95

upper limit

2.45

Variability estimate

Standard error of the mean

Dispersion value

0.381

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

2.19

Confidence interval

level

95%

sides

2-sided

lower limit

1.35

upper limit

3.02

Variability estimate

Standard error of the mean

Dispersion value

0.423

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

1.98

Confidence interval

level

95%

sides

2-sided

lower limit

1.11

upper limit

2.84

Variability estimate

Standard error of the mean

Dispersion value

0.439

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0007

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

1.56

Confidence interval

level

95%

sides

2-sided

lower limit

0.67

upper limit

2.45

Variability estimate

Standard error of the mean

Dispersion value

0.454

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2018

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

0.62

Confidence interval

level

95%

sides

2-sided

lower limit

-0.33

upper limit

1.58

Variability estimate

Standard error of the mean

Dispersion value

0.485

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.6432

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

0.22

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

1.13

Variability estimate

Standard error of the mean

Dispersion value

0.465

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4092

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

0.39

Confidence interval

level

95%

sides

2-sided

lower limit

-0.54

upper limit

1.31

Variability estimate

Standard error of the mean

Dispersion value

0.47

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.107

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

0.82

Confidence interval

level

95%

sides

2-sided

lower limit

-0.18

upper limit

1.81

Variability estimate

Standard error of the mean

Dispersion value

0.506

Secondary: Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Impact Domain Scores at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Top of page

End point title

Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Impact Domain Scores at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

End point description

13-item(felt fatigue,felt weak all over,felt listless,felt tired,had energy,had trouble starting thing as tired,had trouble finishing thing as tired,was able to do usual activity,need to sleep during day,too tired to eat,need help doing usual activity,frustrate by being too tired to do things want to do,had to limit social activity because tired) questionnaire,each item score on 5-point scale: 0(not at all)to 4(very much).Experience domain score calculate:sum 5 item:feel fatigue,feel weak all over,feel listless,feel tired,have energy,impact domain score calculate:summing remaining 8 item.Impact domain score:0(not at all)to 32(very much),high score=less fatigue impact on daily function.Here,change from baseline in impact domain score report.FAS:subject randomize,receive >=1 dose of study drug.On-drug data use,MR not impute.Number of subjects analysed=subject analysed for end point.

End point type

Secondary

End point timeframe

Baseline, Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

End point values	Tofacitinib	Placebo Then Tofacitinib
Number of subjects analysed	132	136
Units: Units on a scale
least squares mean (standard error)
Week 2	1.79 ( 0.334 )	0.17 ( 0.332 )
Week 4	2.47 ( 0.364 )	0.55 ( 0.361 )
Week 8	3.73 ( 0.429 )	0.46 ( 0.428 )
Week 12	3.45 ( 0.440 )	0.41 ( 0.441 )
Week 16	3.68 ( 0.488 )	1.81 ( 0.487 )
Week 24	3.84 ( 0.504 )	2.86 ( 0.501 )
Week 32	4.25 ( 0.489 )	3.80 ( 0.485 )
Week 40	4.70 ( 0.480 )	3.57 ( 0.476 )
Week 48	5.32 ( 0.542 )	3.95 ( 0.538 )

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0002

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

1.62

Confidence interval

level

95%

sides

2-sided

lower limit

0.78

upper limit

2.46

Variability estimate

Standard error of the mean

Dispersion value

0.428

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

1.92

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

2.84

Variability estimate

Standard error of the mean

Dispersion value

0.466

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

3.26

Confidence interval

level

95%

sides

2-sided

lower limit

2.18

upper limit

4.34

Variability estimate

Standard error of the mean

Dispersion value

0.549

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

3.04

Confidence interval

level

95%

sides

2-sided

lower limit

1.93

upper limit

4.15

Variability estimate

Standard error of the mean

Dispersion value

0.564

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0028

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

1.87

Confidence interval

level

95%

sides

2-sided

lower limit

0.65

upper limit

3.09

Variability estimate

Standard error of the mean

Dispersion value

0.621

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1289

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

0.97

Confidence interval

level

95%

sides

2-sided

lower limit

-0.28

upper limit

2.23

Variability estimate

Standard error of the mean

Dispersion value

0.638

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4698

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

0.45

Confidence interval

level

95%

sides

2-sided

lower limit

-0.77

upper limit

1.66

Variability estimate

Standard error of the mean

Dispersion value

0.616

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0616

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

1.13

Confidence interval

level

95%

sides

2-sided

lower limit

-0.06

upper limit

2.32

Variability estimate

Standard error of the mean

Dispersion value

0.603

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0455

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

1.37

Confidence interval

level

95%

sides

2-sided

lower limit

0.03

upper limit

2.71

Variability estimate

Standard error of the mean

Dispersion value

0.681

Secondary: Change From Baseline in Patient's Global Assessment of Disease (PGA) at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Top of page

End point title

Change From Baseline in Patient's Global Assessment of Disease (PGA) at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

End point description

Subjects answered the question, “How active was your spondylitis on average during the last week?. Subject’s response was recorded using a numerical rating scale ranged from 0 (Not Active) to 10 (Very Active), with higher scores indicated more severe disease. FAS: included all subjects who were randomised to the study and received at least one dose of the randomised investigational product (i.e., tofacitinib or placebo). Here, on-drug data was used and missing response was not imputed. Here "number of subjects analysed" signifies subjects analysed for this end point.

End point type

Secondary

End point timeframe

Baseline, Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

End point values	Tofacitinib	Placebo Then Tofacitinib
Number of subjects analysed	132	136
Units: Units on a scale
least squares mean (standard error)
Week 2	-1.21 ( 0.144 )	-0.32 ( 0.144 )
Week 4	-1.85 ( 0.168 )	-0.63 ( 0.167 )
Week 8	-2.14 ( 0.181 )	-0.42 ( 0.181 )
Week 12	-2.37 ( 0.193 )	-0.65 ( 0.193 )
Week 16	-2.47 ( 0.204 )	-0.91 ( 0.204 )
Week 24	-2.76 ( 0.222 )	-2.21 ( 0.221 )
Week 32	-3.04 ( 0.228 )	-2.43 ( 0.226 )
Week 40	-3.04 ( 0.222 )	-2.50 ( 0.220 )
Week 48	-3.47 ( 0.225 )	-2.94 ( 0.223 )

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.88

Confidence interval

level

95%

sides

2-sided

lower limit

-1.25

upper limit

-0.52

Variability estimate

Standard error of the mean

Dispersion value

0.185

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-1.22

Confidence interval

level

95%

sides

2-sided

lower limit

-1.65

upper limit

-0.8

Variability estimate

Standard error of the mean

Dispersion value

0.215

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-1.71

Confidence interval

level

95%

sides

2-sided

lower limit

-2.17

upper limit

-1.26

Variability estimate

Standard error of the mean

Dispersion value

0.232

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-1.72

Confidence interval

level

95%

sides

2-sided

lower limit

-2.2

upper limit

-1.23

Variability estimate

Standard error of the mean

Dispersion value

0.247

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-1.56

Confidence interval

level

95%

sides

2-sided

lower limit

-2.07

upper limit

-1.05

Variability estimate

Standard error of the mean

Dispersion value

0.26

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0483

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.56

Confidence interval

level

95%

sides

2-sided

lower limit

-1.11

upper limit

Variability estimate

Standard error of the mean

Dispersion value

0.281

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0357

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-1.17

upper limit

-0.04

Variability estimate

Standard error of the mean

Dispersion value

0.286

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0508

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.55

Confidence interval

level

95%

sides

2-sided

lower limit

-1.09

upper limit

Variability estimate

Standard error of the mean

Dispersion value

0.278

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0614

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.53

Confidence interval

level

95%

sides

2-sided

lower limit

-1.08

upper limit

0.03

Variability estimate

Standard error of the mean

Dispersion value

0.282

Secondary: Change From Baseline in Patient’s Assessment of Spinal Pain: Total back Pain at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Top of page

End point title

Change From Baseline in Patient’s Assessment of Spinal Pain: Total back Pain at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

End point description

Subjects marked their level of total back pain on a numerical rating scale (NRS) ranged from 0 (no pain) to 10 (most severe pain), with higher scores indicated more severe pain. FAS: included all subjects who were randomised to the study and received at least one dose of the randomised investigational product (i.e., tofacitinib or placebo). Here, on-drug data was used and missing response was not imputed. Here "number of subjects analysed" signifies subjects analysed for this end point.

End point type

Secondary

End point timeframe

Baseline, Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

End point values	Tofacitinib	Placebo Then Tofacitinib
Number of subjects analysed	132	136
Units: Units on a scale
least squares mean (standard error)
Week 2	-1.28 ( 0.145 )	-0.38 ( 0.144 )
Week 4	-2.05 ( 0.164 )	-0.71 ( 0.164 )
Week 8	-2.51 ( 0.173 )	-0.53 ( 0.173 )
Week 12	-2.57 ( 0.192 )	-0.69 ( 0.192 )
Week 16	-2.57 ( 0.191 )	-0.96 ( 0.191 )
Week 24	-2.99 ( 0.206 )	-2.47 ( 0.205 )
Week 32	-3.16 ( 0.212 )	-2.86 ( 0.210 )
Week 40	-3.11 ( 0.217 )	-2.62 ( 0.215 )
Week 48	-3.57 ( 0.220 )	-2.87 ( 0.218 )

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.89

Confidence interval

level

95%

sides

2-sided

lower limit

-1.26

upper limit

-0.53

Variability estimate

Standard error of the mean

Dispersion value

0.186

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-1.34

Confidence interval

level

95%

sides

2-sided

lower limit

-1.75

upper limit

-0.92

Variability estimate

Standard error of the mean

Dispersion value

0.21

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-1.98

Confidence interval

level

95%

sides

2-sided

lower limit

-2.41

upper limit

-1.54

Variability estimate

Standard error of the mean

Dispersion value

0.221

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-1.89

Confidence interval

level

95%

sides

2-sided

lower limit

-2.37

upper limit

-1.4

Variability estimate

Standard error of the mean

Dispersion value

0.245

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-1.62

Confidence interval

level

95%

sides

2-sided

lower limit

-2.1

upper limit

-1.14

Variability estimate

Standard error of the mean

Dispersion value

0.243

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0492

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.51

Confidence interval

level

95%

sides

2-sided

lower limit

-1.03

upper limit

Variability estimate

Standard error of the mean

Dispersion value

0.261

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2614

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-0.82

upper limit

0.22

Variability estimate

Standard error of the mean

Dispersion value

0.266

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0722

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.49

Confidence interval

level

95%

sides

2-sided

lower limit

-1.03

upper limit

0.04

Variability estimate

Standard error of the mean

Dispersion value

0.272

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0121

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-1.24

upper limit

-0.15

Variability estimate

Standard error of the mean

Dispersion value

0.275

Secondary: Change From Baseline in Patient’s Assessment of Spinal Pain: Nocturnal Spinal Pain at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Top of page

End point title

Change From Baseline in Patient’s Assessment of Spinal Pain: Nocturnal Spinal Pain at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

End point description

Subjects marked their level of nocturnal spinal pain on a NRS ranged from 0 (no pain) to 10 (most severe pain), with higher scores indicated more severe pain. FAS: included all subjects who were randomised to the study and received at least one dose of the randomised investigational product (i.e., tofacitinib or placebo). Here, on-drug data was used and missing response was not imputed. Here "number of subjects analysed" signifies subjects analysed for this end point.

End point type

Secondary

End point timeframe

Baseline, Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

End point values	Tofacitinib	Placebo Then Tofacitinib
Number of subjects analysed	132	136
Units: Units on a scale
least squares mean (standard error)
Week 2	-1.24 ( 0.162 )	-0.32 ( 0.161 )
Week 4	-2.15 ( 0.169 )	-0.56 ( 0.167 )
Week 8	-2.61 ( 0.191 )	-0.59 ( 0.190 )
Week 12	-2.60 ( 0.198 )	-0.60 ( 0.199 )
Week 16	-2.67 ( 0.204 )	-0.84 ( 0.204 )
Week 24	-3.07 ( 0.217 )	-2.59 ( 0.215 )
Week 32	-3.17 ( 0.219 )	-2.89 ( 0.217 )
Week 40	-3.20 ( 0.226 )	-2.73 ( 0.224 )
Week 48	-3.52 ( 0.229 )	-3.01 ( 0.227 )

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.92

Confidence interval

level

95%

sides

2-sided

lower limit

-1.33

upper limit

-0.51

Variability estimate

Standard error of the mean

Dispersion value

0.207

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-1.6

Confidence interval

level

95%

sides

2-sided

lower limit

-2.02

upper limit

-1.17

Variability estimate

Standard error of the mean

Dispersion value

0.216

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-2.02

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

-1.54

Variability estimate

Standard error of the mean

Dispersion value

0.244

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-2

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

-1.5

Variability estimate

Standard error of the mean

Dispersion value

0.254

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-1.84

Confidence interval

level

95%

sides

2-sided

lower limit

-2.35

upper limit

-1.32

Variability estimate

Standard error of the mean

Dispersion value

0.26

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0785

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.48

Confidence interval

level

95%

sides

2-sided

lower limit

-1.02

upper limit

0.06

Variability estimate

Standard error of the mean

Dispersion value

0.274

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3047

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.28

Confidence interval

level

95%

sides

2-sided

lower limit

-0.82

upper limit

0.26

Variability estimate

Standard error of the mean

Dispersion value

0.275

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1009

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.47

Confidence interval

level

95%

sides

2-sided

lower limit

-1.02

upper limit

0.09

Variability estimate

Standard error of the mean

Dispersion value

0.283

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0764

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.51

Confidence interval

level

95%

sides

2-sided

lower limit

-1.08

upper limit

0.05

Variability estimate

Standard error of the mean

Dispersion value

0.287

Secondary: Change From Baseline in in Bath Ankylosing Spondylitis Functional Index (BASFI) at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Top of page

End point title

Change From Baseline in in Bath Ankylosing Spondylitis Functional Index (BASFI) at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

End point description

BASFI was a functional index which included 10 items assessing ability of subjects to perform normal daily activities. The first 8 questions/items consider activities related to functional anatomy. The final 2 questions/items assess the subjects’ ability to cope with everyday life. Each item was scored on a scale of 0=easy to 10=impossible. The BASFI total score was calculated as the average score of these 10 individual items. BASFI total score ranged from 0 (easy) to 10 (impossible), where higher scores indicated more severe disease activity. FAS: included all subjects who were randomised to the study and received at least one dose of the randomised investigational product (i.e., tofacitinib or placebo). Here, on-drug data was used and missing response was not imputed. Here "number of subjects analysed" signifies subjects analysed for this end point.

End point type

Secondary

End point timeframe

Baseline, Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

End point values	Tofacitinib	Placebo Then Tofacitinib
Number of subjects analysed	132	136
Units: Units on a scale
least squares mean (standard error)
Week 2	-0.87 ( 0.125 )	-0.45 ( 0.124 )
Week 4	-1.35 ( 0.140 )	-0.58 ( 0.139 )
Week 8	-1.79 ( 0.158 )	-0.69 ( 0.157 )
Week 12	-2.01 ( 0.164 )	-0.71 ( 0.164 )
Week 16	-2.05 ( 0.170 )	-0.82 ( 0.169 )
Week 24	-2.25 ( 0.191 )	-1.91 ( 0.190 )
Week 32	-2.42 ( 0.188 )	-2.16 ( 0.187 )
Week 40	-2.62 ( 0.192 )	-2.23 ( 0.191 )
Week 48	-2.61 ( 0.196 )	-2.32 ( 0.195 )

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0089

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.42

Confidence interval

level

95%

sides

2-sided

lower limit

-0.73

upper limit

-0.11

Variability estimate

Standard error of the mean

Dispersion value

0.159

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.77

Confidence interval

level

95%

sides

2-sided

lower limit

-1.12

upper limit

-0.42

Variability estimate

Standard error of the mean

Dispersion value

0.179

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-1.1

Confidence interval

level

95%

sides

2-sided

lower limit

-1.5

upper limit

-0.7

Variability estimate

Standard error of the mean

Dispersion value

0.202

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-1.29

Confidence interval

level

95%

sides

2-sided

lower limit

-1.71

upper limit

-0.88

Variability estimate

Standard error of the mean

Dispersion value

0.21

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-1.23

Confidence interval

level

95%

sides

2-sided

lower limit

-1.66

upper limit

-0.8

Variability estimate

Standard error of the mean

Dispersion value

0.217

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1686

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.33

Confidence interval

level

95%

sides

2-sided

lower limit

-0.81

upper limit

0.14

Variability estimate

Standard error of the mean

Dispersion value

0.242

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.28

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.26

Confidence interval

level

95%

sides

2-sided

lower limit

-0.72

upper limit

0.21

Variability estimate

Standard error of the mean

Dispersion value

0.238

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1135

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.39

Confidence interval

level

95%

sides

2-sided

lower limit

-0.86

upper limit

0.09

Variability estimate

Standard error of the mean

Dispersion value

0.243

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2496

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.29

Confidence interval

level

95%

sides

2-sided

lower limit

-0.77

upper limit

0.2

Variability estimate

Standard error of the mean

Dispersion value

0.247

Secondary: Change From Baseline in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Inflammation (Morning Stiffness) Score at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Top of page

End point title

Change From Baseline in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Inflammation (Morning Stiffness) Score at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

End point description

BASDAI: validated questionnaire of 6 questions about 5 major symptoms of AS: fatigue; spinal pain; peripheral arthritis; enthesitis, intensity of morning stiffness, duration of morning stiffness. Each question rated:0 (none) to 10 (very severe), high score=high disease activity. BASDAI score calculated by computing the mean of Q5 and Q6 and adding it to sum of questions 1-4. This score then divided by 5. Total BASDAI score ranged from 0=none to 10=very severe disease activity. BASDAI inflammation score derived by taking the mean of response of Q5 and Q6, range from 0 (none) to 10 (very severe), high score=more inflammation (morning stiffness). FAS: included all subjects randomised, received >= 1 dose of investigational product. On-drug data used, MR not imputed. Number of subjects analysed=subjects analysed for this end point.

End point type

Secondary

End point timeframe

Baseline, Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

End point values	Tofacitinib	Placebo Then Tofacitinib
Number of subjects analysed	132	136
Units: Units on a scale
least squares mean (standard error)
Week 2	-1.33 ( 0.149 )	-0.49 ( 0.149 )
Week 4	-2.08 ( 0.164 )	-0.60 ( 0.163 )
Week 8	-2.52 ( 0.178 )	-0.91 ( 0.178 )
Week 12	-2.71 ( 0.185 )	-0.84 ( 0.186 )
Week 16	-2.69 ( 0.185 )	-0.97 ( 0.185 )
Week 24	-2.99 ( 0.193 )	-2.48 ( 0.193 )
Week 32	-3.11 ( 0.200 )	-2.61 ( 0.199 )
Week 40	-3.28 ( 0.204 )	-2.64 ( 0.203 )
Week 48	-3.46 ( 0.214 )	-2.90 ( 0.213 )

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.84

Confidence interval

level

95%

sides

2-sided

lower limit

-1.22

upper limit

-0.47

Variability estimate

Standard error of the mean

Dispersion value

0.191

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-1.48

Confidence interval

level

95%

sides

2-sided

lower limit

-1.89

upper limit

-1.07

Variability estimate

Standard error of the mean

Dispersion value

0.21

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-1.61

Confidence interval

level

95%

sides

2-sided

lower limit

-2.06

upper limit

-1.16

Variability estimate

Standard error of the mean

Dispersion value

0.228

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-1.87

Confidence interval

level

95%

sides

2-sided

lower limit

-2.34

upper limit

-1.4

Variability estimate

Standard error of the mean

Dispersion value

0.237

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-1.72

Confidence interval

level

95%

sides

2-sided

lower limit

-2.18

upper limit

-1.25

Variability estimate

Standard error of the mean

Dispersion value

0.236

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0385

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.51

Confidence interval

level

95%

sides

2-sided

lower limit

-0.99

upper limit

-0.03

Variability estimate

Standard error of the mean

Dispersion value

0.245

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0463

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-1

upper limit

-0.01

Variability estimate

Standard error of the mean

Dispersion value

0.252

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0126

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.65

Confidence interval

level

95%

sides

2-sided

lower limit

-1.15

upper limit

-0.14

Variability estimate

Standard error of the mean

Dispersion value

0.257

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0372

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.56

Confidence interval

level

95%

sides

2-sided

lower limit

-1.09

upper limit

-0.03

Variability estimate

Standard error of the mean

Dispersion value

0.268

Secondary: Percentage of Subjects Achieving ASAS 5/6 Response at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Top of page

End point title

Percentage of Subjects Achieving ASAS 5/6 Response at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

End point description

ASAS 5/6 consisted of 6 domain: 4 used in ASAS20–PGA of Disease (assess disease activity on scale of 0 [not active] to 10 [very active], high score=more disease activity), Spinal Pain (total back pain) (on scale of 0 [no pain] to 10 [most severe pain], high score=more severity), Function (using BASFI which assessed subject’s level of ability on scale of 0 [easy] to 10 [impossible], low score= better functional health), Inflammation (using BASDAI, mean of Q 5 and 6, which assess disease activity on scale of 0 [none] to 10 [severe], high score=more disease activity), CRP (measured in mg per liter), Spinal mobility measured in cm, calculated as mean of right and left measurements of lateral spinal flexion from BASMI. ASAS 5/6: define as >=20% improvement in at least 5 domain. FAS: include all subject who were randomize, received >=1 dose of study drug. On-drug data used, MR=NR.

End point type

Secondary

End point timeframe

Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

End point values	Tofacitinib	Placebo Then Tofacitinib
Number of subjects analysed	133	136
Units: Percentage of subjects
number (not applicable)
Week 2	16.54	2.94
Week 4	35.34	6.62
Week 8	41.35	8.09
Week 12	45.86	9.56
Week 16	43.61	7.35
Week 24	49.62	44.12
Week 32	51.13	53.68
Week 40	48.87	50.74
Week 48	43.61	44.85

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 2: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

269

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0001

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

13.6

Confidence interval

level

95%

sides

2-sided

lower limit

6.68

upper limit

20.52

Variability estimate

Standard error of the mean

Dispersion value

3.53

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 4: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

269

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

28.79

Confidence interval

level

95%

sides

2-sided

lower limit

19.78

upper limit

37.8

Variability estimate

Standard error of the mean

Dispersion value

4.6

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 8: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

269

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

33.31

Confidence interval

level

95%

sides

2-sided

lower limit

23.84

upper limit

42.78

Variability estimate

Standard error of the mean

Dispersion value

4.83

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 12: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

269

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

36.37

Confidence interval

level

95%

sides

2-sided

lower limit

26.67

upper limit

46.07

Variability estimate

Standard error of the mean

Dispersion value

4.95

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 16: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

269

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

36.34

Confidence interval

level

95%

sides

2-sided

lower limit

27.05

upper limit

45.63

Variability estimate

Standard error of the mean

Dispersion value

4.74

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 24: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

269

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3498

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

5.6

Confidence interval

level

95%

sides

2-sided

lower limit

-6.14

upper limit

17.35

Variability estimate

Standard error of the mean

Dispersion value

5.99

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 32: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

269

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.6835

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

-2.4

Confidence interval

level

95%

sides

2-sided

lower limit

-13.96

upper limit

9.15

Variability estimate

Standard error of the mean

Dispersion value

5.89

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 40: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

269

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7704

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

-1.75

Confidence interval

level

95%

sides

2-sided

lower limit

-13.47

upper limit

9.98

Variability estimate

Standard error of the mean

Dispersion value

5.98

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 48: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

269

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8492

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

-1.13

Confidence interval

level

95%

sides

2-sided

lower limit

-12.8

upper limit

10.53

Variability estimate

Standard error of the mean

Dispersion value

5.95

Secondary: Percentage of Subjects Achieving ASAS Partial Remission at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Top of page

End point title

Percentage of Subjects Achieving ASAS Partial Remission at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

End point description

Partial remission define as a score of 2 or less (on a scale of 0-10, 0=no disease activity, 10=high disease activity) in each of the 4 domain in ASAS. These 4 domain include: PGA (assess disease activity on a scale of 0 [not active] to 10 [very active], high score=more disease activity), total back pain (on a scale of 0 [no pain] to 10 [most severe pain], high score=more severity), Function (using BASFI which assessed subject’s level of ability on a scale of 0 [easy] to 10 [impossible], low score= better functional health), Inflammation (using BASDAI, mean of Q 5 and 6, which assess disease activity on a scale of 0 [none] to 10 [severe], high score=more disease activity). FAS: include all subjects who were randomised to the study, received at least one dose of the randomised investigational product (i.e., tofacitinib or placebo). Here, on-drug data used, MR=NR.

End point type

Secondary

End point timeframe

Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

End point values	Tofacitinib	Placebo Then Tofacitinib
Number of subjects analysed	133	136
Units: Percentage of subjects
number (not applicable)
Week 2	2.26	0
Week 4	4.51	0
Week 8	7.52	1.47
Week 12	15.04	2.94
Week 16	15.04	2.94
Week 24	21.80	11.76
Week 32	23.31	15.44
Week 40	24.06	16.91
Week 48	23.31	17.65

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 2: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

269

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1692

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

2.24

Confidence interval

level

95%

sides

2-sided

lower limit

-0.95

upper limit

5.43

Variability estimate

Standard error of the mean

Dispersion value

1.63

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 4: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

269

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0289

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

4.46

Confidence interval

level

95%

sides

2-sided

lower limit

0.46

upper limit

8.46

Variability estimate

Standard error of the mean

Dispersion value

2.04

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 8: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

269

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0199

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

6.02

Confidence interval

level

95%

sides

2-sided

lower limit

0.95

upper limit

11.09

Variability estimate

Standard error of the mean

Dispersion value

2.59

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 12: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

269

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0005

Method

Difference in percentage

Parameter type

Difference in percentage

Point estimate

12.03

Confidence interval

level

95%

sides

2-sided

lower limit

5.26

upper limit

18.81

Variability estimate

Standard error of the mean

Dispersion value

3.46

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 16: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

269

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0005

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

12.05

Confidence interval

level

95%

sides

2-sided

lower limit

5.29

upper limit

18.8

Variability estimate

Standard error of the mean

Dispersion value

3.45

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 32: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

269

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.095

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

7.93

Confidence interval

level

95%

sides

2-sided

lower limit

-1.38

upper limit

17.24

Variability estimate

Standard error of the mean

Dispersion value

4.75

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 24: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

269

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0253

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

10.03

Confidence interval

level

95%

sides

2-sided

lower limit

1.24

upper limit

18.83

Variability estimate

Standard error of the mean

Dispersion value

4.49

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 40: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

269

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1377

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

7.21

Confidence interval

level

95%

sides

2-sided

lower limit

-2.31

upper limit

16.73

Variability estimate

Standard error of the mean

Dispersion value

4.86

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 48: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

269

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2472

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

5.68

Confidence interval

level

95%

sides

2-sided

lower limit

-3.94

upper limit

15.3

Variability estimate

Standard error of the mean

Dispersion value

4.91

Secondary: Change From Baseline in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Total Score at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

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End point title

Change From Baseline in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Total Score at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

End point description

BASDAI was validated questionnaire that consisted of 6 questions pertaining to 5 major symptoms of AS: fatigue; spinal pain; peripheral arthritis; enthesitis, intensity of morning stiffness, duration of morning stiffness. Each question was rated using numerical rating scale from 0 (none) to 10 (very severe), high score=high disease activity. BASDAI score was calculated by computing mean of Q 5 and 6, adding it to sum of questions 1 to 4. This score was then divided by 5. The total BASDAI score was ranged from 0= none to 10= very severe, where high score indicated high disease activity. FAS: included all subjects who were randomised to the study and received at least one dose of the randomised investigational product. Here, on-drug data was used and missing response was not imputed. Here "number of subjects analysed" = subjects analysed for this end point.

End point type

Secondary

End point timeframe

Baseline, Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

End point values	Tofacitinib	Placebo Then Tofacitinib
Number of subjects analysed	132	136
Units: Units on a scale
least squares mean (standard error)
Week 2	-1.25 ( 0.127 )	-0.52 ( 0.126 )
Week 4	-1.95 ( 0.146 )	-0.67 ( 0.145 )
Week 8	-2.32 ( 0.164 )	-0.82 ( 0.163 )
Week 12	-2.49 ( 0.172 )	-0.81 ( 0.172 )
Week 16	-2.55 ( 0.175 )	-1.11 ( 0.174 )
Week 24	-2.81 ( 0.185 )	-2.41 ( 0.184 )
Week 32	-2.94 ( 0.191 )	-2.53 ( 0.190 )
Week 40	-3.09 ( 0.193 )	-2.63 ( 0.192 )
Week 48	-3.30 ( 0.199 )	-2.80 ( 0.197 )

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.73

Confidence interval

level

95%

sides

2-sided

lower limit

-1.05

upper limit

-0.41

Variability estimate

Standard error of the mean

Dispersion value

0.163

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-1.28

Confidence interval

level

95%

sides

2-sided

lower limit

-1.65

upper limit

-0.91

Variability estimate

Standard error of the mean

Dispersion value

0.187

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-1.5

Confidence interval

level

95%

sides

2-sided

lower limit

-1.92

upper limit

-1.09

Variability estimate

Standard error of the mean

Dispersion value

0.21

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-1.68

Confidence interval

level

95%

sides

2-sided

lower limit

-2.11

upper limit

-1.24

Variability estimate

Standard error of the mean

Dispersion value

0.221

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-1.44

Confidence interval

level

95%

sides

2-sided

lower limit

-1.88

upper limit

-1

Variability estimate

Standard error of the mean

Dispersion value

0.223

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.088

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-0.86

upper limit

0.06

Variability estimate

Standard error of the mean

Dispersion value

0.235

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0921

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.41

Confidence interval

level

95%

sides

2-sided

lower limit

-0.88

upper limit

0.07

Variability estimate

Standard error of the mean

Dispersion value

0.241

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0597

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.46

Confidence interval

level

95%

sides

2-sided

lower limit

-0.94

upper limit

0.02

Variability estimate

Standard error of the mean

Dispersion value

0.243

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0492

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.49

Confidence interval

level

95%

sides

2-sided

lower limit

-0.99

upper limit

Variability estimate

Standard error of the mean

Dispersion value

0.25

Secondary: Percentage of Subjects Achieving Bath Ankylosing Spondylitis Disease Activity Index 50 (BASDAI50) Response at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

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End point title

Percentage of Subjects Achieving Bath Ankylosing Spondylitis Disease Activity Index 50 (BASDAI50) Response at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

End point description

BASDAI: validated questionnaire that consist of 6 question pertaining to 5 major symptom of AS: fatigue; spinal pain; peripheral arthritis; enthesitis, intensity of morning stiffness, duration of morning stiffness. Each question was rate using numerical rating scale from 0 (none) to 10 (very severe), high score=high disease activity. BASDAI score calculate by computing mean of Q5 and Q6 and adding it to sum of questions 1 to 4. This score was then divided by 5. Total BASDAI score range from 0= none to 10= very severe, high score=high disease activity. BASDAI50 response defined as decrease of >=50% from Baseline in BASDAI score at specified time point. Percentage of subjects with BASDAI 50 response at specified weeks are reported. FAS: included all subjects who were randomized, received at least one dose of randomised investigational product. Here, on-drug data was used, MR=NR.

End point type

Secondary

End point timeframe

Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

End point values	Tofacitinib	Placebo Then Tofacitinib
Number of subjects analysed	133	136
Units: Percentage of subjects
number (not applicable)
Week 2	12.03	3.68
Week 4	29.32	6.62
Week 8	39.85	11.03
Week 12	42.86	11.03
Week 16	42.86	17.65
Week 24	47.37	36.76
Week 32	51.13	41.18
Week 40	52.63	39.71
Week 48	51.13	40.44

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 2: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

269

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0116

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

8.31

Confidence interval

level

95%

sides

2-sided

lower limit

1.86

upper limit

14.77

Variability estimate

Standard error of the mean

Dispersion value

3.29

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 4: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

269

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

22.74

Confidence interval

level

95%

sides

2-sided

lower limit

13.99

upper limit

31.49

Variability estimate

Standard error of the mean

Dispersion value

4.46

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 8: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

269

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

28.87

Confidence interval

level

95%

sides

2-sided

lower limit

19.09

upper limit

38.66

Variability estimate

Standard error of the mean

Dispersion value

4.99

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 12: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

269

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

31.93

Confidence interval

level

95%

sides

2-sided

lower limit

22.28

upper limit

41.58

Variability estimate

Standard error of the mean

Dispersion value

4.92

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 16: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

269

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

25.28

Confidence interval

level

95%

sides

2-sided

lower limit

14.82

upper limit

35.75

Variability estimate

Standard error of the mean

Dispersion value

5.34

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 24: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

269

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0683

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

10.71

Confidence interval

level

95%

sides

2-sided

lower limit

-0.8

upper limit

22.23

Variability estimate

Standard error of the mean

Dispersion value

5.88

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 32: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

269

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0906

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

10.05

Confidence interval

level

95%

sides

2-sided

lower limit

-1.59

upper limit

21.7

Variability estimate

Standard error of the mean

Dispersion value

5.94

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 40: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

269

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0282

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

13.03

Confidence interval

level

95%

sides

2-sided

lower limit

1.39

upper limit

24.66

Variability estimate

Standard error of the mean

Dispersion value

5.94

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 48: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

269

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0719

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

10.77

Confidence interval

level

95%

sides

2-sided

lower limit

-0.96

upper limit

22.49

Variability estimate

Standard error of the mean

Dispersion value

5.98

Secondary: Percentage of Subjects With Ankylosing Spondylitis Disease Activity Score Using C-Reactive Protein (ASDAS[CRP]) Clinically Important Improvement Response at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

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End point title

Percentage of Subjects With Ankylosing Spondylitis Disease Activity Score Using C-Reactive Protein (ASDAS[CRP]) Clinically Important Improvement Response at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

End point description

Derive by BASDAI(6-item questionnaire:disease activity on scale:0[none]-10[severe], high score=more disease activity),PGA(disease activity on a scale of 0[not active]-10[very active],high score=more disease activity),using formula,0.121xBack Pain(Q2 of BASDAI)+0.058xDuration of Morning Stiffness(Q6 of BASDAI)+0.110xPGA+0.073xPeripheral Pain/Swelling(Q3 of BASDAI)+0.579 x Ln(hsCRP mg/L+1).If hsCRP value <2mg/L,set to 2mg/L in formula.Range:>=0.636-no defined upper limit.Negative change from baseline=decrease in disease activity;positive change from baseline=increase in disease activity.ASDAS(CRP) clinically important improvement:decrease from Baseline >=1.1 unit in ASDAS(CRP) score.FAS:subject randomised,receive >=1 dose of study drug.Analysis include subject with baseline ASDAS(CRP)>=1.736 unit.On-drug data used, MR=NR. Number of subject analysed=subject analysed for end point.

End point type

Secondary

End point timeframe

Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

End point values	Tofacitinib	Placebo Then Tofacitinib
Number of subjects analysed	132	136
Units: Percentage of subjects
number (not applicable)
Week 2	39.39	6.62
Week 4	53.03	12.50
Week 8	59.85	14.71
Week 12	60.61	15.44
Week 16	61.36	19.12
Week 24	65.15	60.29
Week 32	65.91	61.76
Week 40	63.64	57.35
Week 48	58.33	52.94

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 2: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

32.79

Confidence interval

level

95%

sides

2-sided

lower limit

23.48

upper limit

42.11

Variability estimate

Standard error of the mean

Dispersion value

4.75

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 4: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

40.53

Confidence interval

level

95%

sides

2-sided

lower limit

30.37

upper limit

50.7

Variability estimate

Standard error of the mean

Dispersion value

5.19

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 8: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

45.22

Confidence interval

level

95%

sides

2-sided

lower limit

35.03

upper limit

55.41

Variability estimate

Standard error of the mean

Dispersion value

5.2

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 12: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

45.23

Confidence interval

level

95%

sides

2-sided

lower limit

34.97

upper limit

55.49

Variability estimate

Standard error of the mean

Dispersion value

5.23

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 16: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

42.3

Confidence interval

level

95%

sides

2-sided

lower limit

31.73

upper limit

52.88

Variability estimate

Standard error of the mean

Dispersion value

5.4

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 24: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3967

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

4.96

Confidence interval

level

95%

sides

2-sided

lower limit

-6.51

upper limit

16.42

Variability estimate

Standard error of the mean

Dispersion value

5.85

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 32: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4442

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

4.34

Confidence interval

level

95%

sides

2-sided

lower limit

-6.78

upper limit

15.46

Variability estimate

Standard error of the mean

Dispersion value

5.67

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 40: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.281

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

6.38

Confidence interval

level

95%

sides

2-sided

lower limit

-5.22

upper limit

17.97

Variability estimate

Standard error of the mean

Dispersion value

5.92

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 48: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3514

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

5.54

Confidence interval

level

95%

sides

2-sided

lower limit

-6.12

upper limit

17.2

Variability estimate

Standard error of the mean

Dispersion value

5.95

Secondary: Percentage of Subjects Ankylosing Spondylitis Disease Activity Score Using C-Reactive Protein (ASDAS[CRP]) Major Improvement Response at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

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End point title

Percentage of Subjects Ankylosing Spondylitis Disease Activity Score Using C-Reactive Protein (ASDAS[CRP]) Major Improvement Response at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

End point description

Derive by BASDAI:6-item questionnaire measure disease activity;scale:0[none]-10[severe],high score=more disease activity,PGA:measure disease activity;scale 0[not active]-10[very active],high score=more disease activity),by using the formula,0.121xBack Pain(Q2 of BASDAI)+0.058xDuration of Morning Stiffness(Q6 of BASDAI)+0.110xPGA+0.073xPeripheral Pain/Swelling(Q3 of BASDAI)+0.579 x Ln(hsCRP mg/L+1).If hsCRP value <2mg/L, set to 2mg/L in formula.Range:>=0.636 to no defined upper limit.Negative change from baseline=decrease in disease activity;positive change from baseline=increase in disease activity.ASDAS(CRP) major improvement defined as response if decrease from Baseline of >=2.0units.FAS:all subject randomise,receive >=1 dose of study drug.Analysis include subject with baseline ASDAS(CRP)>=2.636unit.On-drug data use, MR=NR. Number of subject analysed=subject analysed for end point.

End point type

Secondary

End point timeframe

Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

End point values	Tofacitinib	Placebo Then Tofacitinib
Number of subjects analysed	123	129
Units: Percentage of subjects
number (not applicable)
Week 2	8.94	0.00
Week 4	17.89	1.55
Week 8	22.76	2.33
Week 12	26.02	3.10
Week 16	30.08	4.65
Week 24	34.15	24.81
Week 32	36.59	34.11
Week 40	39.02	31.78
Week 48	33.33	28.68

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 2: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

252

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0013

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

8.84

Confidence interval

level

95%

sides

2-sided

lower limit

3.46

upper limit

14.21

Variability estimate

Standard error of the mean

Dispersion value

2.74

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 4: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

252

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

16.25

Confidence interval

level

95%

sides

2-sided

lower limit

9.13

upper limit

23.36

Variability estimate

Standard error of the mean

Dispersion value

3.63

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 8: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

252

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

20.31

Confidence interval

level

95%

sides

2-sided

lower limit

12.41

upper limit

28.2

Variability estimate

Standard error of the mean

Dispersion value

4.03

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 12: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

252

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

22.77

Confidence interval

level

95%

sides

2-sided

lower limit

14.46

upper limit

31.08

Variability estimate

Standard error of the mean

Dispersion value

4.24

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 16: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

252

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

25.28

Confidence interval

level

95%

sides

2-sided

lower limit

16.47

upper limit

34.1

Variability estimate

Standard error of the mean

Dispersion value

4.5

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 24: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

252

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0941

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

9.41

Confidence interval

level

95%

sides

2-sided

lower limit

-1.61

upper limit

20.43

Variability estimate

Standard error of the mean

Dispersion value

5.62

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 32: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

252

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.6727

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

2.52

Confidence interval

level

95%

sides

2-sided

lower limit

-9.17

upper limit

14.21

Variability estimate

Standard error of the mean

Dispersion value

5.96

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 40: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

252

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2213

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

7.29

Confidence interval

level

95%

sides

2-sided

lower limit

-4.39

upper limit

18.98

Variability estimate

Standard error of the mean

Dispersion value

5.96

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 48: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

252

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4137

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

4.7

Confidence interval

level

95%

sides

2-sided

lower limit

-6.58

upper limit

15.98

Variability estimate

Standard error of the mean

Dispersion value

5.76

Secondary: Percentage of Subjects Ankylosing Spondylitis Disease Activity Score Using C-Reactive Protein (ASDAS[CRP]) Inactive Disease Response at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Top of page

End point title

Percentage of Subjects Ankylosing Spondylitis Disease Activity Score Using C-Reactive Protein (ASDAS[CRP]) Inactive Disease Response at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

End point description

Derived by BASDAI:6-item questionnaire;disease activity on scale:0[none]-10[severe], high score=more disease activity,PGA:disease activity on a scale of 0[not active]-10[very active],high score=more disease activity,using formula,0.121xBack Pain(Q2 of BASDAI)+0.058xDuration of Morning Stiffness(Q6 of BASDAI)+0.110xPGA+0.073xPeripheral Pain/Swelling(Q3 of BASDAI)+0.579 x Ln(hsCRP mg/L+1).If hsCRP values <2mg/L, set to 2mg/L in formula.Range:>=0.636-no defined upper limit.Negative change from baseline=decrease in disease activity;positive change from baseline=increase in disease activity. ASDAS(CRP) inactive disease:defined as response if actual ASDAS(CRP) <1.3 units. FAS:all subject randomised,receive >=1 dose of study drug.Analysis includes subjects with baseline ASDAS(CRP)>=1.3unit.On-drug data used, MR=NR.

End point type

Secondary

End point timeframe

Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

End point values	Tofacitinib	Placebo Then Tofacitinib
Number of subjects analysed	133	136
Units: Percentage of subjects
number (not applicable)
Week 2	0.75	0.00
Week 4	3.76	0.00
Week 8	6.02	0.74
Week 12	11.28	0.74
Week 16	6.77	0.00
Week 24	12.78	11.76
Week 32	18.05	13.24
Week 40	17.29	16.91
Week 48	15.04	13.24

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 2: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

269

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5518

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

0.75

Confidence interval

level

95%

sides

2-sided

lower limit

-1.73

upper limit

3.24

Variability estimate

Standard error of the mean

Dispersion value

1.27

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 4: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

269

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0524

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

3.72

Confidence interval

level

95%

sides

2-sided

lower limit

-0.04

upper limit

7.47

Variability estimate

Standard error of the mean

Dispersion value

1.92

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 8: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

269

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0216

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

5.25

Confidence interval

level

95%

sides

2-sided

lower limit

0.77

upper limit

9.73

Variability estimate

Standard error of the mean

Dispersion value

2.29

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 12: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

269

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0003

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

10.48

Confidence interval

level

95%

sides

2-sided

lower limit

4.8

upper limit

16.17

Variability estimate

Standard error of the mean

Dispersion value

2.9

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 16: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

269

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0047

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

6.69

Confidence interval

level

95%

sides

2-sided

lower limit

2.05

upper limit

11.33

Variability estimate

Standard error of the mean

Dispersion value

2.37

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 24: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

269

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7883

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

1.07

Confidence interval

level

95%

sides

2-sided

lower limit

-6.74

upper limit

8.88

Variability estimate

Standard error of the mean

Dispersion value

3.98

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 32: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

269

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2708

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

4.85

Confidence interval

level

95%

sides

2-sided

lower limit

-3.78

upper limit

13.48

Variability estimate

Standard error of the mean

Dispersion value

4.4

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 40: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

269

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9226

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

0.44

Confidence interval

level

95%

sides

2-sided

lower limit

-8.48

upper limit

9.36

Variability estimate

Standard error of the mean

Dispersion value

4.55

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 48: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

269

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.663

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

1.84

Confidence interval

level

95%

sides

2-sided

lower limit

-6.44

upper limit

10.13

Variability estimate

Standard error of the mean

Dispersion value

4.23

Secondary: Change from baseline in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) at Weeks 4, 8, 12, 16, 24, 32, 40 and 48

Top of page

End point title

Change from baseline in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) at Weeks 4, 8, 12, 16, 24, 32, 40 and 48

End point description

MASES:index use to measure severity of enthesitis. Enthesitis is inflammation of enthuses (heels). MASES assess 13 sites for enthesitis. Sites assess include 1st costochondral joint (left [l]/right [r]), 7th costochondral joint (l/r), posterior superior iliac spine (l/r), posterior anterior iliac spine (l/r), iliac crest (l/r), proximal insertion of Achilles tendon (l/r) and 5th lumbar spinous process. Each site was grade for presence (1) and absence (0) of tenderness yielding total MASES score ranging from 0 (no tenderness) to 13 (worst possible score) with high score =more severe tenderness. FAS: include all subject who were randomised to study, received at least one dose of randomised investigational product. Analysis include only subject with baseline MASES > 0. Here, on-drug data was use, MR was not impute. Here number of subjects analysed=subjects analysed for this end point.

End point type

Secondary

End point timeframe

Baseline, Weeks 4, 8, 12, 16, 24, 32, 40 and 48

End point values	Tofacitinib	Placebo Then Tofacitinib
Number of subjects analysed	70	79
Units: Units on a scale
least squares mean (standard error)
Week 4	-1.42 ( 0.264 )	-0.59 ( 0.244 )
Week 8	-2.02 ( 0.275 )	-1.28 ( 0.255 )
Week 12	-1.89 ( 0.289 )	-1.17 ( 0.271 )
Week 16	-1.94 ( 0.288 )	-1.41 ( 0.272 )
Week 24	-2.50 ( 0.251 )	-2.32 ( 0.240 )
Week 32	-2.73 ( 0.204 )	-2.54 ( 0.200 )
Week 40	-2.73 ( 0.189 )	-2.75 ( 0.183 )
Week 48	-2.87 ( 0.225 )	-2.56 ( 0.222 )

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

149

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0099

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.84

Confidence interval

level

95%

sides

2-sided

lower limit

-1.47

upper limit

-0.2

Variability estimate

Standard error of the mean

Dispersion value

0.319

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

149

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0275

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.74

Confidence interval

level

95%

sides

2-sided

lower limit

-1.4

upper limit

-0.08

Variability estimate

Standard error of the mean

Dispersion value

0.332

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

149

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.042

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.72

Confidence interval

level

95%

sides

2-sided

lower limit

-1.41

upper limit

-0.03

Variability estimate

Standard error of the mean

Dispersion value

0.35

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

149

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1309

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.53

Confidence interval

level

95%

sides

2-sided

lower limit

-1.22

upper limit

0.16

Variability estimate

Standard error of the mean

Dispersion value

0.349

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

149

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5566

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.18

Confidence interval

level

95%

sides

2-sided

lower limit

-0.78

upper limit

0.42

Variability estimate

Standard error of the mean

Dispersion value

0.305

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

149

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4497

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.19

Confidence interval

level

95%

sides

2-sided

lower limit

-0.68

upper limit

0.3

Variability estimate

Standard error of the mean

Dispersion value

0.248

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

149

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9272

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

0.02

Confidence interval

level

95%

sides

2-sided

lower limit

-0.43

upper limit

0.47

Variability estimate

Standard error of the mean

Dispersion value

0.227

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

149

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2539

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.31

Confidence interval

level

95%

sides

2-sided

lower limit

-0.85

upper limit

0.23

Variability estimate

Standard error of the mean

Dispersion value

0.273

Secondary: Change from baseline in Swollen Joint Count (SJC) at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Top of page

End point title

Change from baseline in Swollen Joint Count (SJC) at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

End point description

Swollen joint count was an assessment on 44 joints (sternoclaviculars, acromioclaviculars, shoulders, elbows, wrists, metacarpophalangeals, thumb interphalangeal, proximal interphalangeals, knees, ankles, and metatarsophalangeals). Each joint was assessed for swelling as: Present or Absent. Artificial joints were not assessed. FAS: included all subjects who were randomised to the study and received at least one dose of the randomised investigational product (i.e., tofacitinib or placebo). Analysis included only subjects with baseline SJC(44) > 0. Here, on-drug data was used and missing response was not imputed. Here "number of subjects analysed" signifies subjects analysed for this end point.

End point type

Secondary

End point timeframe

Baseline, Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

End point values	Tofacitinib	Placebo Then Tofacitinib
Number of subjects analysed	33	38
Units: Joint count
least squares mean (standard error)
Week 2	-1.71 ( 0.376 )	-2.09 ( 0.358 )
Week 4	-1.90 ( 0.418 )	-2.23 ( 0.398 )
Week 8	-2.39 ( 0.456 )	-2.45 ( 0.438 )
Week 12	-2.79 ( 0.428 )	-2.45 ( 0.419 )
Week 16	-3.35 ( 0.475 )	-2.79 ( 0.465 )
Week 24	-2.81 ( 0.346 )	-3.32 ( 0.335 )
Week 32	-2.45 ( 0.357 )	-3.21 ( 0.341 )
Week 40	-3.04 ( 0.289 )	-3.34 ( 0.274 )
Week 48	-3.31 ( 0.176 )	-3.82 ( 0.174 )

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4379

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

0.37

Confidence interval

level

95%

sides

2-sided

lower limit

-0.58

upper limit

1.33

Variability estimate

Standard error of the mean

Dispersion value

0.479

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.534

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

0.33

Confidence interval

level

95%

sides

2-sided

lower limit

-0.73

upper limit

1.39

Variability estimate

Standard error of the mean

Dispersion value

0.532

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9148

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

0.06

Confidence interval

level

95%

sides

2-sided

lower limit

-1.1

upper limit

1.22

Variability estimate

Standard error of the mean

Dispersion value

0.582

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5409

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.34

Confidence interval

level

95%

sides

2-sided

lower limit

-1.43

upper limit

0.76

Variability estimate

Standard error of the mean

Dispersion value

0.548

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3555

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.57

Confidence interval

level

95%

sides

2-sided

lower limit

-1.78

upper limit

0.65

Variability estimate

Standard error of the mean

Dispersion value

0.607

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2485

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

0.51

Confidence interval

level

95%

sides

2-sided

lower limit

-0.36

upper limit

1.38

Variability estimate

Standard error of the mean

Dispersion value

0.436

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0866

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

0.76

Confidence interval

level

95%

sides

2-sided

lower limit

-0.11

upper limit

1.63

Variability estimate

Standard error of the mean

Dispersion value

0.435

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4101

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-0.42

upper limit

1.01

Variability estimate

Standard error of the mean

Dispersion value

0.356

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0237

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

0.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.07

upper limit

0.94

Variability estimate

Standard error of the mean

Dispersion value

0.217

Secondary: Change from baseline in Spinal Mobility (Chest Expansion) at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Top of page

End point title

Change from baseline in Spinal Mobility (Chest Expansion) at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

End point description

Chest expansion (measured in centimetres (cm), is defined as difference in thoracic circumference during full expiration versus full inspiration. This was measured at 4th intercostal space. Difference between maximal inspiration and expiration of two attempts was recorded. Better of two attempts was used to calculate chest expansion which was defined to be greater than or equal to 0 cm with no defined maximum/upper limit. Greater chest circumference corresponds to higher score indicated more spinal mobility/better health status (measured as Chest Expansion in cm). FAS: included all subjects who were randomised to the study and received at least one dose of the randomised investigational product (i.e., tofacitinib or placebo). Here, on-drug data was used and missing response was not imputed. Here "number of subjects analysed" signifies subjects analysed for this end point.

End point type

Secondary

End point timeframe

Baseline, Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

End point values	Tofacitinib	Placebo Then Tofacitinib
Number of subjects analysed	132	136
Units: Centimetre
least squares mean (standard error)
Week 2	0.22 ( 0.084 )	-0.09 ( 0.083 )
Week 4	0.25 ( 0.094 )	-0.07 ( 0.094 )
Week 8	0.46 ( 0.114 )	0.22 ( 0.114 )
Week 12	0.57 ( 0.102 )	0.25 ( 0.102 )
Week 16	0.59 ( 0.128 )	0.38 ( 0.127 )
Week 24	0.62 ( 0.133 )	0.63 ( 0.132 )
Week 32	0.61 ( 0.149 )	0.71 ( 0.148 )
Week 40	0.75 ( 0.132 )	0.68 ( 0.131 )
Week 48	0.50 ( 0.127 )	0.47 ( 0.125 )

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0043

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

0.31

Confidence interval

level

95%

sides

2-sided

lower limit

0.1

upper limit

0.52

Variability estimate

Standard error of the mean

Dispersion value

0.107

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0072

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

0.33

Confidence interval

level

95%

sides

2-sided

lower limit

0.09

upper limit

0.56

Variability estimate

Standard error of the mean

Dispersion value

0.121

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1101

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

0.23

Confidence interval

level

95%

sides

2-sided

lower limit

-0.05

upper limit

0.52

Variability estimate

Standard error of the mean

Dispersion value

0.146

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2032

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

0.21

Confidence interval

level

95%

sides

2-sided

lower limit

-0.11

upper limit

0.53

Variability estimate

Standard error of the mean

Dispersion value

0.162

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0147

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

0.32

Confidence interval

level

95%

sides

2-sided

lower limit

0.06

upper limit

0.58

Variability estimate

Standard error of the mean

Dispersion value

0.13

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9345

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.01

Confidence interval

level

95%

sides

2-sided

lower limit

-0.34

upper limit

0.32

Variability estimate

Standard error of the mean

Dispersion value

0.168

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5968

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.47

upper limit

0.27

Variability estimate

Standard error of the mean

Dispersion value

0.187

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7047

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

0.06

Confidence interval

level

95%

sides

2-sided

lower limit

-0.26

upper limit

0.39

Variability estimate

Standard error of the mean

Dispersion value

0.166

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.807

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

0.04

Confidence interval

level

95%

sides

2-sided

lower limit

-0.27

upper limit

0.35

Variability estimate

Standard error of the mean

Dispersion value

0.157

Secondary: Change From Baseline in EuroQol 5 Dimensions 3 Levels (EQ-5D-3L) Score at Weeks 16 and 48

Top of page

End point title

Change From Baseline in EuroQol 5 Dimensions 3 Levels (EQ-5D-3L) Score at Weeks 16 and 48

End point description

EQ-5D-3L, a health profile questionnaire was used to assess quality of life along 5 dimensions. Subjects rated 5 aspects of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) by choosing from 3 answering options (1=no problems; 2=some problems; 3=extreme problems). The mean of the summed score ranged from 1 to 3 with "1" corresponding to no problems and "3" corresponding to severe problems in the 5 dimensions, where higher score indicates more severe problems. FAS: included all subjects who were randomised to the study and received at least one dose of the randomised investigational product (i.e., tofacitinib or placebo). Here, on-drug data was used and missing response was not imputed. Here "number of subjects analysed" signifies subjects analysed for this end point.

End point type

Secondary

End point timeframe

Baseline, Weeks 16 and 48

End point values	Tofacitinib	Placebo Then Tofacitinib
Number of subjects analysed	129	131
Units: Units on a scale
least squares mean (standard error)
Week 16: Mobility	-0.23 ( 0.044 )	-0.06 ( 0.044 )
Week 16: Self-Care	-0.21 ( 0.043 )	-0.20 ( 0.043 )
Week 16: Usual Activities	-0.18 ( 0.046 )	-0.09 ( 0.046 )
Week 16: Pain/Discomfort	-0.30 ( 0.036 )	-0.12 ( 0.036 )
Week 16: Anxiety/Depression	-0.11 ( 0.048 )	-0.10 ( 0.048 )
Week 48: Mobility	-0.32 ( 0.051 )	-0.26 ( 0.050 )
Week 48: Self-Care	-0.33 ( 0.048 )	-0.33 ( 0.047 )
Week 48: Usual Activities	-0.32 ( 0.053 )	-0.34 ( 0.053 )
Week 48: Pain/Discomfort	-0.37 ( 0.047 )	-0.36 ( 0.047 )
Week 48: Anxiety/Depression	-0.17 ( 0.054 )	-0.21 ( 0.053 )

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 16, Mobility: Analysis performed using ANCOVA model which included fixed effects of treatment group, stratification factor derived from clinical database, and baseline value.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

260

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.003

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

-0.17

Confidence interval

level

95%

sides

2-sided

lower limit

-0.28

upper limit

-0.06

Variability estimate

Standard error of the mean

Dispersion value

0.055

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 16, Self-Care: Analysis performed using ANCOVA model which included fixed effects of treatment group, stratification factor derived from clinical database, and baseline value.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

260

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.897

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

-0.01

Confidence interval

level

95%

sides

2-sided

lower limit

-0.11

upper limit

0.1

Variability estimate

Standard error of the mean

Dispersion value

0.055

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 16, Usual Activities: Analysis performed using ANCOVA model which included fixed effects of treatment group, stratification factor derived from clinical database, and baseline value.

Comparison groups

Placebo Then Tofacitinib v Tofacitinib

Number of subjects included in analysis

260

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1437

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

-0.09

Confidence interval

level

95%

sides

2-sided

lower limit

-0.2

upper limit

0.03

Variability estimate

Standard error of the mean

Dispersion value

0.058

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 16, Pain/Discomfort: Analysis performed using ANCOVA model which included fixed effects of treatment group, stratification factor derived from clinical database, and baseline value.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

260

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

-0.18

Confidence interval

level

95%

sides

2-sided

lower limit

-0.27

upper limit

-0.09

Variability estimate

Standard error of the mean

Dispersion value

0.046

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 16, Anxiety/Depression: Analysis performed using ANCOVA model which included fixed effects of treatment group, stratification factor derived from clinical database, and baseline value.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

260

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8445

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

-0.01

Confidence interval

level

95%

sides

2-sided

lower limit

-0.13

upper limit

0.11

Variability estimate

Standard error of the mean

Dispersion value

0.061

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 48, Mobility: Analysis performed using MMRM which included fixed effect of treatment group, visit, and treatment-group by visit interaction, stratification factor derived from clinical database, stratification-factor by visit interaction, baseline value, and baseline-value by visit interaction.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

260

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3473

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.06

Confidence interval

level

95%

sides

2-sided

lower limit

-0.19

upper limit

0.07

Variability estimate

Standard error of the mean

Dispersion value

0.064

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 48, Self-Care: Analysis performed using MMRM which included fixed effect of treatment group, visit, and treatment-group by visit interaction, stratification factor derived from clinical database, stratification-factor by visit interaction, baseline value, and baseline-value by visit interaction.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

260

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9834

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.12

upper limit

0.12

Variability estimate

Standard error of the mean

Dispersion value

0.059

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 48, Usual Activities: Analysis performed using MMRM which included fixed effect of treatment group, visit, and treatment-group by visit interaction, stratification factor derived from clinical database, stratification-factor by visit interaction, baseline value, and baseline-value by visit interaction.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

260

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7364

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

0.02

Confidence interval

level

95%

sides

2-sided

lower limit

-0.11

upper limit

0.15

Variability estimate

Standard error of the mean

Dispersion value

0.066

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 48, Pain/Discomfort: Analysis performed using MMRM which included fixed effect of treatment group, visit, and treatment-group by visit interaction, stratification factor derived from clinical database, stratification-factor by visit interaction, baseline value, and baseline-value by visit interaction.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

260

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8075

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-0.01

Confidence interval

level

95%

sides

2-sided

lower limit

-0.13

upper limit

0.1

Variability estimate

Standard error of the mean

Dispersion value

0.059

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 48, Anxiety/Depression: Analysis performed using MMRM which included fixed effect of treatment group, visit, and treatment-group by visit interaction, stratification factor derived from clinical database, stratification-factor by visit interaction, baseline value, and baseline-value by visit interaction.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

260

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5461

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

0.04

Confidence interval

level

95%

sides

2-sided

lower limit

-0.09

upper limit

0.17

Variability estimate

Standard error of the mean

Dispersion value

0.067

Secondary: Change From Baseline in EuroQol Visual Analogue Scale (EQ-VAS) Score (mm) at Weeks 16 and 48

Top of page

End point title

Change From Baseline in EuroQol Visual Analogue Scale (EQ-VAS) Score (mm) at Weeks 16 and 48

End point description

EQ-5D-3L, a health profile questionnaire was used to assess quality of life along 5 dimensions. Its second part included EQ-VAS. EQ-VAS recorded the subject’s self-rated health on a VAS ranging from 0 mm (worst imaginable health state) to 100 mm (best imaginable health state), with higher scores indicating better health state. FAS: included all subjects who were randomised to the study and received at least one dose of the randomised investigational product (i.e., tofacitinib or placebo). Here, on-drug data was used and missing response was not imputed. Here "number of subjects analysed" signifies subjects analysed for this end point and 'n'= subject analysed for this end point for specified time point.

End point type

Secondary

End point timeframe

Baseline, Weeks 16 and 48

End point values	Tofacitinib	Placebo Then Tofacitinib
Number of subjects analysed	129	130
Units: Millimetre (mm)
least squares mean (standard error)
Week 16 (n=128, 130)	13.00 ( 1.840 )	2.89 ( 1.840 )
Week 48 (n=129, 130)	20.64 ( 1.879 )	18.00 ( 1.862 )

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2608

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

2.63

Confidence interval

level

95%

sides

2-sided

lower limit

-1.97

upper limit

7.24

Variability estimate

Standard error of the mean

Dispersion value

2.337

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 16: Analysis performed using ANCOVA model which included fixed effects of treatment group, stratification factor derived from clinical database, and baseline value.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

10.11

Confidence interval

level

95%

sides

2-sided

lower limit

5.52

upper limit

14.7

Variability estimate

Standard error of the mean

Dispersion value

2.331

Secondary: Change From Baseline in Work Productivity and Activity Impairment (WPAI): Percent Work Time Missed Due to Health Problem at Weeks 16 and 48

Top of page

End point title

Change From Baseline in Work Productivity and Activity Impairment (WPAI): Percent Work Time Missed Due to Health Problem at Weeks 16 and 48

End point description

WPAI: 6-item questionnaire assessed degree to which AS affect work productivity,regular activities over past 7 day.Questions:Q1=currently employed;Q2=hours missed due to health problems;Q3=hours missed due to other reasons;Q4=hours actually worked;Q5=degree health affected productivity while working(0-10 scale,high number=less productivity);Q6=degree health affected regular activities(0-10 scale,high number=greater impairment of regular activities).Percent work time missed due to health problem was subscale,calculated: Q2/(Q2+Q4) for those who were currently employed.Subscale score expressed as impairment percentage(range:0-100%),high number=greater impairment,less productivity.FAS:included all subject randomised to study,received at least 1 dose of tofacitinib or placebo.On-drug data used,MR not imputed. Here, number of subjects analysed signifies subject analysed for this endpoint and 'n'= subject analysed for this end point for specified time point.

End point type

Secondary

End point timeframe

Baseline, Weeks 16 and 48

End point values	Tofacitinib	Placebo Then Tofacitinib
Number of subjects analysed	77	85
Units: Units on a scale
least squares mean (standard error)
Week 16 (n=74, 81)	-3.65 ( 2.659 )	0.88 ( 2.622 )
Week 48 (n=77, 85)	-8.10 ( 2.136 )	-5.79 ( 2.047 )

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

162

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3651

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-2.31

Confidence interval

level

95%

sides

2-sided

lower limit

-7.34

upper limit

2.72

Variability estimate

Standard error of the mean

Dispersion value

2.54

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 16: Analysis performed using ANCOVA model which included fixed effects of treatment group, stratification factor derived from clinical database, and baseline value.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

162

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1784

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

-4.53

Confidence interval

level

95%

sides

2-sided

lower limit

-11.15

upper limit

2.09

Variability estimate

Standard error of the mean

Dispersion value

3.35

Secondary: Change From Baseline in Work Productivity and Activity Impairment (WPAI): Percent Impairment While Working due to Health Problem at Weeks 16 and 48

Top of page

End point title

Change From Baseline in Work Productivity and Activity Impairment (WPAI): Percent Impairment While Working due to Health Problem at Weeks 16 and 48

End point description

WPAI:6-item questionnaire to assess degree to which AS affect work productivity,regular activities in past 7 day.Questions:Q1=currently employed;Q2=hours missed due to health problems;Q3=hours missed due to other reasons;Q4=hours actually worked;Q5=degree health affected productivity while working(0-10 scale,high number=less productivity);Q6=degree health affected regular activities(0-10 scale,high number=greater impairment of regular activities).% Impairment while working due to Health Problem was subscale,calculated:Q5/10 for those who were currently employed,actually worked in past 7 days.Subscale score expressed as impairment %(range: 0-100%)where high number=greater impairment,less productivity. FAS:include all subject randomise to study,receive at least 1 dose of tofacitinib/placebo.On-drug data used,MR not imputed. Here, number of subjects analysed signifies subjects analysed for this end point and 'n'= subject analysed for this end point for specified time point.

End point type

Secondary

End point timeframe

Baseline, Weeks 16 and 48

End point values	Tofacitinib	Placebo Then Tofacitinib
Number of subjects analysed	75	82
Units: Units on a scale
least squares mean (standard error)
Week 16 (n=71, 77)	-19.83 ( 2.274 )	-6.94 ( 2.303 )
Week 48 (n=75, 82)	-25.35 ( 2.769 )	-23.00 ( 2.656 )

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 16: Analysis performed using ANCOVA model which included fixed effects of treatment group, stratification factor derived from clinical database, and baseline value.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

157

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

-12.89

Confidence interval

level

95%

sides

2-sided

lower limit

-18.59

upper limit

-7.19

Variability estimate

Standard error of the mean

Dispersion value

2.884

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

157

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4788

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-2.36

Confidence interval

level

95%

sides

2-sided

lower limit

-8.92

upper limit

4.21

Variability estimate

Standard error of the mean

Dispersion value

3.318

Secondary: Change From Baseline in Work Productivity and Activity Impairment (WPAI): Percent Overall Work Impairment due to Health Problem at Weeks 16 and 48

Top of page

End point title

Change From Baseline in Work Productivity and Activity Impairment (WPAI): Percent Overall Work Impairment due to Health Problem at Weeks 16 and 48

End point description

WPAI:6-item questionnaire to assess degree to which AS affect work productivity,regular activities in past 7 day.Questions:Q1=currently employed;Q2=hours missed due to health problems;Q3=hours missed due to other reasons;Q4=hours actually worked;Q5=degree health affected productivity while working(0-10 scale,high number=less productivity);Q6=degree health affected regular activities(0-10 scale,high number=greater impairment of regular activities).% overall work impairment due to health problem was subscale, calculated:Q2/(Q2+Q4)+[(1-Q2/(Q2+Q4))×(Q5/10)] for those who were currently employed.Subscale score expressed as impairment %(range:0-100%) where higher number=greater impairment. FAS:include all subject randomise to study,receive at least 1 dose of tofacitinib/placebo.On-drug data used,MR not imputed. Here, number of subjects analysed signifies subjects analysed for this end point and 'n'= subject analysed for this end point for specified time point.

End point type

Secondary

End point timeframe

Baseline, Weeks 16 and 48

End point values	Tofacitinib	Placebo Then Tofacitinib
Number of subjects analysed	75	82
Units: Units on a scale
least squares mean (standard error)
Week 16 (n=71, 76)	-21.49 ( 2.508 )	-7.64 ( 2.559 )
Week 48 (n=75, 82)	-27.63 ( 3.005 )	-23.22 ( 2.890 )

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 16: Analysis performed using ANCOVA model which included fixed effects of treatment group, stratification factor derived from clinical database, and baseline value.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

157

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

-13.85

Confidence interval

level

95%

sides

2-sided

lower limit

-20.18

upper limit

-7.52

Variability estimate

Standard error of the mean

Dispersion value

3.202

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

157

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2244

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-4.41

Confidence interval

level

95%

sides

2-sided

lower limit

-11.56

upper limit

2.74

Variability estimate

Standard error of the mean

Dispersion value

3.613

Secondary: Change From Baseline in Work Productivity and Activity Impairment (WPAI): Percent Activity Impairment due to Health Problem at Weeks 16 and 48

Top of page

End point title

Change From Baseline in Work Productivity and Activity Impairment (WPAI): Percent Activity Impairment due to Health Problem at Weeks 16 and 48

End point description

WPAI:6-item questionnaire to assess degree to which AS affect work productivity,regular activities in past 7 day.Questions:Q1=currently employed;Q2=hours missed due to health problems;Q3=hours missed due to other reasons;Q4=hours actually worked;Q5=degree health affected productivity while working(0-10 scale,high number=less productivity);Q6=degree health affected regular activities(0-10 scale,high number=greater impairment of regular activities)% activity impairment due to health problem was subscale,calculated:Q6/10 for all respondents.Subscale score expressed as impairment %(range: 0-100%) where higher numbers=greater impairment. FAS:include all subject randomise to study,receive at least 1 dose of tofacitinib/placebo.On-drug data used,MR not imputed. Here, "number of subject analysed" signify subjects analysed for this end point.

End point type

Secondary

End point timeframe

Baseline, Weeks 16 and 48

End point values	Tofacitinib	Placebo Then Tofacitinib
Number of subjects analysed	129	131
Units: Units on a scale
least squares mean (standard error)
Week 16	-19.03 ( 1.969 )	-5.63 ( 1.968 )
Week 48	-27.37 ( 2.339 )	-19.77 ( 2.310 )

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Week 16: Analysis performed using ANCOVA model which included fixed effects of treatment group, stratification factor derived from clinical database, and baseline value.

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

260

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

-13.4

Confidence interval

level

95%

sides

2-sided

lower limit

-18.3

upper limit

-8.5

Variability estimate

Standard error of the mean

Dispersion value

2.488

Tofacitinib vs Placebo Then Tofacitinib

Statistical analysis description

Comparison groups

Tofacitinib v Placebo Then Tofacitinib

Number of subjects included in analysis

260

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0095

Method

Mixed models analysis

Parameter type

LS mean difference

Point estimate

-7.6

Confidence interval

level

95%

sides

2-sided

lower limit

-13.32

upper limit

-1.88

Variability estimate

Standard error of the mean

Dispersion value

2.905

Adverse events

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Timeframe for reporting adverse events

For the first 2 arms: (tofacitinib and Placebo [up to Week 16]): Baseline to Week 16 and for the next 2 arms (tofacitinib and placebo then tofacitinib [Day 1 to Week 48]): Baseline to Week 48

Adverse event reporting additional description

Same event may appear as AE, serious AE, what is presented are distinct events. Event may be categorized as serious in 1, and non-serious in another or 1 subject may have experienced both. Safety analysis set. Non-serious AEs are reported as >5% as cut off.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

.23.0

Reporting group title

Tofacitinib: Up to Week 16

Reporting group description

Subjects received tofacitinib 5 mg tablets twice daily for 16 weeks.

Reporting group title

Placebo: Up to Week 16

Reporting group description

Subjects received tofacitinib matching placebo tablets, twice daily for 16 weeks.

Reporting group title

Tofacitinib: Day 1 to Week 48

Reporting group description

Subjects received tofacitinib 5 mg tablets twice daily for 48 weeks.

Reporting group title

Placebo Then Tofacitinib: Day 1 to Week 48

Reporting group description

Subjects received tofacitinib matching placebo tablets, twice daily for 16 weeks followed by tofacitinib tablets 5 mg, twice daily for next 32 weeks (i.e. up to Week 48).

Serious adverse events	Tofacitinib: Up to Week 16	Placebo: Up to Week 16	Tofacitinib: Day 1 to Week 48	Placebo Then Tofacitinib: Day 1 to Week 48
Total subjects affected by serious adverse events
subjects affected / exposed	2 / 133 (1.50%)	1 / 136 (0.74%)	7 / 133 (5.26%)	2 / 136 (1.47%)
number of deaths (all causes)	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0
Injury, poisoning and procedural complications
Rib fracture
subjects affected / exposed	0 / 133 (0.00%)	0 / 136 (0.00%)	1 / 133 (0.75%)	0 / 136 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Thoracic vertebral fracture
subjects affected / exposed	0 / 133 (0.00%)	1 / 136 (0.74%)	0 / 133 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Migraine
subjects affected / exposed	0 / 133 (0.00%)	0 / 136 (0.00%)	1 / 133 (0.75%)	0 / 136 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Condition aggravated
subjects affected / exposed	0 / 133 (0.00%)	1 / 136 (0.74%)	0 / 133 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ear and labyrinth disorders
Hypoacusis
subjects affected / exposed	1 / 133 (0.75%)	0 / 136 (0.00%)	1 / 133 (0.75%)	0 / 136 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal adhesions
subjects affected / exposed	0 / 133 (0.00%)	0 / 136 (0.00%)	1 / 133 (0.75%)	0 / 136 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Pneumothorax
subjects affected / exposed	0 / 133 (0.00%)	0 / 136 (0.00%)	1 / 133 (0.75%)	0 / 136 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Hyperplastic cholecystopathy
subjects affected / exposed	0 / 133 (0.00%)	0 / 136 (0.00%)	1 / 133 (0.75%)	0 / 136 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Subcutaneous emphysema
subjects affected / exposed	0 / 133 (0.00%)	0 / 136 (0.00%)	1 / 133 (0.75%)	0 / 136 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Ureterolithiasis
subjects affected / exposed	0 / 133 (0.00%)	0 / 136 (0.00%)	1 / 133 (0.75%)	0 / 136 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Spinal osteoarthritis
subjects affected / exposed	0 / 133 (0.00%)	0 / 136 (0.00%)	0 / 133 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Meningitis aseptic
subjects affected / exposed	1 / 133 (0.75%)	0 / 136 (0.00%)	1 / 133 (0.75%)	0 / 136 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Tofacitinib: Up to Week 16	Placebo: Up to Week 16	Tofacitinib: Day 1 to Week 48	Placebo Then Tofacitinib: Day 1 to Week 48
Total subjects affected by non serious adverse events
subjects affected / exposed	23 / 133 (17.29%)	26 / 136 (19.12%)	51 / 133 (38.35%)	52 / 136 (38.24%)
Investigations
Alanine aminotransferase increased
subjects affected / exposed	0 / 133 (0.00%)	0 / 136 (0.00%)	8 / 133 (6.02%)	2 / 136 (1.47%)
occurrences all number	0	0	15	2
Protein urine present
subjects affected / exposed	0 / 133 (0.00%)	0 / 136 (0.00%)	8 / 133 (6.02%)	4 / 136 (2.94%)
occurrences all number	0	0	9	5
Nervous system disorders
Headache
subjects affected / exposed	0 / 133 (0.00%)	0 / 136 (0.00%)	5 / 133 (3.76%)	7 / 136 (5.15%)
occurrences all number	0	0	5	7
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	0 / 133 (0.00%)	0 / 136 (0.00%)	10 / 133 (7.52%)	8 / 136 (5.88%)
occurrences all number	0	0	10	8
Abdominal pain upper
subjects affected / exposed	0 / 133 (0.00%)	0 / 136 (0.00%)	2 / 133 (1.50%)	7 / 136 (5.15%)
occurrences all number	0	0	2	8
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	1 / 133 (0.75%)	8 / 136 (5.88%)	2 / 133 (1.50%)	9 / 136 (6.62%)
occurrences all number	1	9	2	12
Infections and infestations
Upper respiratory tract infection
subjects affected / exposed	14 / 133 (10.53%)	10 / 136 (7.35%)	21 / 133 (15.79%)	18 / 136 (13.24%)
occurrences all number	17	10	28	23
Nasopharyngitis
subjects affected / exposed	9 / 133 (6.77%)	10 / 136 (7.35%)	11 / 133 (8.27%)	17 / 136 (12.50%)
occurrences all number	11	12	14	23

More information

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Were there any global substantial amendments to the protocol? Yes

03 Apr 2020

This global amendment incorporates venous thromboembolism (VTE) risk factor checks. Pfizer has determined that VTE is identified as an important identified risk/dose dependent adverse drug reaction for tofacitinib.

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.

None reported

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Clinical trials

Clinical Trial Results: A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Study of the Efficacy and Safety of Tofacitinib in Subjects With Active Ankylosing Spondylitis (AS)

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of Subjects Achieving Assessment of SpondyloArthritis International Society (ASAS)20 Response at Week 16

Primary: Percentage of Subjects Achieving Assessment of SpondyloArthritis International Society (ASAS)20 Response at Week 16

Secondary: Percentage of Subjects Achieving Ankylosing Spondylitis (ASAS)40 Response at Week 16

Secondary: Percentage of Subjects Achieving Ankylosing Spondylitis (ASAS)40 Response at Week 16

Secondary: Number of Subjects With Treatment Emergent Adverse Events (AEs)

Secondary: Number of Subjects With Treatment Emergent Adverse Events (AEs)

Secondary: Number of Subjects With Treatment Emergent Adverse Events (AEs) by Severity

Secondary: Number of Subjects With Treatment Emergent Adverse Events (AEs) by Severity

Secondary: Number of Subjects With Laboratory Abnormalities (Without Regard to Baseline Abnormality)

Secondary: Number of Subjects With Laboratory Abnormalities (Without Regard to Baseline Abnormality)

Secondary: Number of Subjects With Vital Signs Abnormalities

Secondary: Number of Subjects With Vital Signs Abnormalities

Secondary: Number of Subjects with Abnormalities in Physical Examination

Secondary: Number of Subjects with Abnormalities in Physical Examination

Secondary: Number of Subjects With Electrocardiogram (ECG) Abnormalities

Secondary: Number of Subjects With Electrocardiogram (ECG) Abnormalities

Secondary: Percentage of Subjects Achieving ASAS20 Response at Weeks 2, 4, 8, 12, 24, 32, 40 and 48

Secondary: Percentage of Subjects Achieving ASAS20 Response at Weeks 2, 4, 8, 12, 24, 32, 40 and 48

Secondary: Percentage of Subjects Achieving ASAS40 Response at Weeks 2, 4, 8, 12, 24, 32, 40 and 48

Secondary: Percentage of Subjects Achieving ASAS40 Response at Weeks 2, 4, 8, 12, 24, 32, 40 and 48

Secondary: Change From Baseline in Ankylosing Spondylitis Disease Activity Score using C-Reactive Protein (ASDAS[CRP]) at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Secondary: Change From Baseline in Ankylosing Spondylitis Disease Activity Score using C-Reactive Protein (ASDAS[CRP]) at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Secondary: Change From Baseline in High Sensitivity C-Reactive Protein (hsCRP) at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Secondary: Change From Baseline in High Sensitivity C-Reactive Protein (hsCRP) at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Secondary: Change From Baseline in Ankylosing Spondylitis Quality of Life (ASQoL) Score at Weeks 16 and 48

Secondary: Change From Baseline in Ankylosing Spondylitis Quality of Life (ASQoL) Score at Weeks 16 and 48

Secondary: Change From Baseline in Short-Form-36 Health Survey-Version 2 Acute (SF-36v2) Score at Weeks 16 and 48

Secondary: Change From Baseline in Short-Form-36 Health Survey-Version 2 Acute (SF-36v2) Score at Weeks 16 and 48

Secondary: Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) Scores: Cervical Rotation Angle at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Secondary: Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) Scores: Cervical Rotation Angle at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Secondary: Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) Scores: Intermalleolar Distance at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Secondary: Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) Scores: Intermalleolar Distance at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Secondary: Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) Scores: Lateral Spinal Flexion at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Secondary: Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) Scores: Lateral Spinal Flexion at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Secondary: Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) Scores: Lumbar Flexion (Modified Schober) at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Secondary: Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) Scores: Lumbar Flexion (Modified Schober) at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Secondary: Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) Scores: Tragus-to-wall Distance at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Secondary: Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) Scores: Tragus-to-wall Distance at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Secondary: Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) Linear Method Total Score at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Secondary: Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) Linear Method Total Score at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Secondary: Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Total Scores at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Secondary: Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Total Scores at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Secondary: Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Experience Domain Scores at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Secondary: Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Experience Domain Scores at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Secondary: Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Impact Domain Scores at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Secondary: Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Impact Domain Scores at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Secondary: Change From Baseline in Patient's Global Assessment of Disease (PGA) at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Secondary: Change From Baseline in Patient's Global Assessment of Disease (PGA) at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Secondary: Change From Baseline in Patient’s Assessment of Spinal Pain: Total back Pain at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Secondary: Change From Baseline in Patient’s Assessment of Spinal Pain: Total back Pain at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Secondary: Change From Baseline in Patient’s Assessment of Spinal Pain: Nocturnal Spinal Pain at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Secondary: Change From Baseline in Patient’s Assessment of Spinal Pain: Nocturnal Spinal Pain at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Secondary: Change From Baseline in in Bath Ankylosing Spondylitis Functional Index (BASFI) at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Secondary: Change From Baseline in in Bath Ankylosing Spondylitis Functional Index (BASFI) at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Secondary: Change From Baseline in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Inflammation (Morning Stiffness) Score at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Secondary: Change From Baseline in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Inflammation (Morning Stiffness) Score at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Secondary: Percentage of Subjects Achieving ASAS 5/6 Response at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Secondary: Percentage of Subjects Achieving ASAS 5/6 Response at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Secondary: Percentage of Subjects Achieving ASAS Partial Remission at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Secondary: Percentage of Subjects Achieving ASAS Partial Remission at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Secondary: Change From Baseline in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Total Score at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Secondary: Change From Baseline in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Total Score at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Secondary: Percentage of Subjects Achieving Bath Ankylosing Spondylitis Disease Activity Index 50 (BASDAI50) Response at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Secondary: Percentage of Subjects Achieving Bath Ankylosing Spondylitis Disease Activity Index 50 (BASDAI50) Response at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Secondary: Percentage of Subjects With Ankylosing Spondylitis Disease Activity Score Using C-Reactive Protein (ASDAS[CRP]) Clinically Important Improvement Response at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Secondary: Percentage of Subjects With Ankylosing Spondylitis Disease Activity Score Using C-Reactive Protein (ASDAS[CRP]) Clinically Important Improvement Response at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Secondary: Percentage of Subjects Ankylosing Spondylitis Disease Activity Score Using C-Reactive Protein (ASDAS[CRP]) Major Improvement Response at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Secondary: Percentage of Subjects Ankylosing Spondylitis Disease Activity Score Using C-Reactive Protein (ASDAS[CRP]) Major Improvement Response at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Secondary: Percentage of Subjects Ankylosing Spondylitis Disease Activity Score Using C-Reactive Protein (ASDAS[CRP]) Inactive Disease Response at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Secondary: Percentage of Subjects Ankylosing Spondylitis Disease Activity Score Using C-Reactive Protein (ASDAS[CRP]) Inactive Disease Response at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Clinical Trial Results:
A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Study of the Efficacy and Safety of Tofacitinib in Subjects With Active Ankylosing Spondylitis (AS)