Efficacy and Safety of Tofacitinib in Subjects With Active Ankylosing Spondylitis (AS)

• ClinicalTrials.gov Identifier: NCT03502616
• Recruitment Status: Completed
• First Posted: April 18, 2018
• Results First Posted: January 11, 2021
• Last Update Posted: September 17, 2021
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Ankylosing Spondylitis
• Intervention: Drug: Tofacitinib
• Enrollment: 270

Participant Flow

Recruitment Details
Pre-assignment Details	Safety data was planned to be collected and reported for both: Week 0 to Week 16 and from Week 0 to Week 48.

Arm/Group Title	Tofacitinib	Placebo Then Tofacitinib
Arm/Group Description	Participants received Tofacitinib tablets 5 milligram (mg), twice daily for 48 weeks.	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).
Period Title: Up to Week 16
Started	134	136
Treated	133	136
Completed	132	133
Not Completed	2	3
Reason Not Completed
Withdrawal by Subject	1	2
Lost to Follow-up	0	1
Randomized, but not treated	1	0
Period Title: Week 16 to Week 48
Started	132	133
Treated	132	133
Completed	125	127
Not Completed	7	6
Reason Not Completed
Withdrawal by Subject	6	6
Lost to Follow-up	1	0

Baseline Characteristics

Arm/Group Title		Tofacitinib	Placebo Then Tofacitinib	Total
Arm/Group Description		Participants received Tofacitinib tablets 5 milligram (mg), twice daily for 48 weeks.	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).	Total of all reporting groups
Overall Number of Baseline Participants		133	136	269
Baseline Analysis Population Description		Safety analysis set: included all participants who were randomized and received at least one dose of the investigational product (that is [i.e.], tofacitinib or placebo).
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	133 participants	136 participants	269 participants
		42.2 (11.85)	40.0 (11.06)	41.1 (11.49)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	133 participants	136 participants	269 participants
	Female	17 12.8%	28 20.6%	45 16.7%
	Male	116 87.2%	108 79.4%	224 83.3%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	133 participants	136 participants	269 participants
	White	107 80.5%	106 77.9%	213 79.2%
	Asian	25 18.8%	30 22.1%	55 20.4%
	Not reported	1 0.8%	0 0.0%	1 0.4%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Achieving Assessment of SpondyloArthritis International Society (ASAS)20 Response at Week 16
Description	ASAS20 assess 4 domains: Patient Global Assessment of Disease (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 (Bath Ankylosing Spondylitis Functional Index [BASFI]; participant's level of ability on scale of 0 [easy] to 10 [impossible], low score= better functional health) and Inflammation (morning stiffness, Mean of Question [Q]5 and Q6 of Bath Ankylosing Spondylitis Disease Activity Index [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: greater than or equal to (>=) 20 percent (%) improvement from baseline in disease activity and absolute change of >=1 unit in >=3 domains and no worsening of >=20% and an absolute change of >=1 unit in remaining domain.
Time Frame	Week 16

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): included all participants who were randomized to the study and received at least one dose of the randomized investigational product (i.e., tofacitinib or placebo). Here, on-drug data was used and missing response (MR) was considered to be Non-response (NR) (MR=NR).

Arm/Group Title	Tofacitinib	Placebo Then Tofacitinib
Arm/Group Description:	Participants received Tofacitinib tablets 5 milligram (mg), twice daily for 48 weeks.	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).
Overall Number of Participants Analyzed	133	136
Measure Type: Number; Unit of Measure: Percentage of participants
	56.39	29.41

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via Cochran-Mantel-Haenszel (CMH) approach.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in percentage
	Estimated Value	27.08
	Confidence Interval	(2-Sided) 95%; 15.89 to 38.28
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 5.71
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Percentage of Participants Achieving Ankylosing Spondylitis (ASAS)40 Response at Week 16
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 participant'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.
Time Frame	Week 16

Outcome Measure Data

Analysis Population Description

FAS: included all participants who were randomized to the study and received at least one dose of the randomized investigational product (i.e., tofacitinib or placebo). Here, on-drug data was used and missing response (MR) was considered to be Non-response (NR) (MR=NR).

Arm/Group Title	Tofacitinib	Placebo Then Tofacitinib
Arm/Group Description:	Participants received Tofacitinib tablets 5 milligram (mg), twice daily for 48 weeks.	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).
Overall Number of Participants Analyzed	133	136
Measure Type: Number; Unit of Measure: Percentage of participants
	40.60	12.50

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in percentage
	Estimated Value	28.17
	Confidence Interval	(2-Sided) 95%; 18.26 to 38.09
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 5.06
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	Number of Participants With Treatment Emergent Adverse Events (AEs)
Description	An AE: any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. As per National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03, severity was graded as Grade 1: asymptomatic/mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily living (ADL); Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. Treatment-emergent were events between first dose of study drug and up to 48 weeks that were absent before treatment or that worsened relative to pretreatment state.
Time Frame	Baseline up to Week 16 and Baseline up to Week 48

Outcome Measure Data

Analysis Population Description

Safety analysis set: included all participants who were randomized and received at least one dose of the investigational product (i.e., tofacitinib or placebo).

Arm/Group Title	Tofacitinib	Placebo Then Tofacitinib
Arm/Group Description:	Participants received Tofacitinib tablets 5 milligram (mg), twice daily for 48 weeks.	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).
Overall Number of Participants Analyzed	133	136
Measure Type: Count of Participants; Unit of Measure: Participants
Up to Week 16	73 54.9%	70 51.5%
Up to Week 48	103 77.4%	93 68.4%

4. Secondary Outcome

Title	Number of Participants With Treatment Emergent Adverse Events (AEs) by Severity
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 participant's usual function, moderate: Interfered to some extent with participant's usual function and severe: Interfered significantly with participant's usual function.
Time Frame	Baseline up to Week 16 and Baseline up to Week 48

Outcome Measure Data

Analysis Population Description

Safety analysis set: included all participants who were randomized and received at least one dose of the investigational product (i.e., tofacitinib or placebo).

Arm/Group Title	Tofacitinib	Placebo Then Tofacitinib
Arm/Group Description:	Participants received Tofacitinib tablets 5 milligram (mg), twice daily for 48 weeks.	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).
Overall Number of Participants Analyzed	133	136
Measure Type: Count of Participants; Unit of Measure: Participants
Up to Week 16: Mild	53 39.8%	52 38.2%
Up to Week 16: Moderate	18 13.5%	18 13.2%
Up to Week 16: Severe	2 1.5%	0 0.0%
Up to Week 48: Mild	57 42.9%	57 41.9%
Up to Week 48: Moderate	40 30.1%	36 26.5%
Up to Week 48: Severe	6 4.5%	0 0.0%

5. Secondary Outcome

Title	Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)
Description	Hematology (Hemoglobin, Hematocrit, Erythrocyte, Lymphocyte/Leukocyte, Neutrophil/Leukocyte <0.8*Lower limit of normal (LLN), Reticulocyte >1.5*Upper limit of normal (ULN), Erythrocyte Mean Corpuscular Volume, Erythrocyte Mean Corpuscular Hemoglobin, Erythrocyte Mean Corpuscular HGB Concentration <0.9*LLN, >1.1*ULN, Reticulocyte/Erythrocyte, 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, Erythrocyte, Leukocyte >=20, Granular Cast, Hyaline Cast>1.
Time Frame	Baseline up to Week 16 and Baseline up to Week 48

Outcome Measure Data

Analysis Population Description

Safety analysis set: included all participants who were randomized and received at least one dose of the investigational product (i.e., tofacitinib or placebo). Here "Overall number of participants analyzed" signifies participants evaluable for this outcome measure.

Arm/Group Title	Tofacitinib	Placebo Then Tofacitinib
Arm/Group Description:	Participants received Tofacitinib tablets 5 milligram (mg), twice daily for 48 weeks.	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).
Overall Number of Participants Analyzed	132	136
Measure Type: Count of Participants; Unit of Measure: Participants
Up to Week 16	106 80.3%	129 94.9%
Up to Week 48	126 95.5%	131 96.3%

6. Secondary Outcome

Title	Number of Participants With Vital Signs Abnormalities
Description	Criteria for abnormalities in vital signs: Pulse rate <40 beats per minute (bpm) to >120 bpm, Sitting Diastolic blood pressure < 50 millimeter of mercury (mmHg), increase and decrease in change from baseline of >= 20mmHg, sitting systolic blood pressure < 90 mmHg, increase and decrease in change from baseline of >= 30mmHg.
Time Frame	Baseline up to Week 16 and Baseline up to Week 48

Outcome Measure Data

Analysis Population Description

Safety analysis set: included all participants who were randomized and received at least one dose of the investigational product (i.e., tofacitinib or placebo). Here "Overall number of participants analyzed" signifies participants evaluable for this outcome measure.

Arm/Group Title	Tofacitinib	Placebo Then Tofacitinib
Arm/Group Description:	Participants received Tofacitinib tablets 5 milligram (mg), twice daily for 48 weeks.	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).
Overall Number of Participants Analyzed	132	136
Measure Type: Count of Participants; Unit of Measure: Participants
Up to Week 16, Pulse rate: <40 bpm	0 0.0%	0 0.0%
Up to Week 16, Pulse rate: >120 bpm	0 0.0%	0 0.0%
Up to Week 16, Sitting diastolic blood pressure: <50 mmHg	0 0.0%	0 0.0%
Up to Week 16, Sitting diastolic blood pressure: Change >= 20mmHg increase	2 1.5%	4 2.9%
Up to Week 16, Sitting diastolic blood pressure: Change >= 20mmHg decrease	6 4.5%	4 2.9%
Up to Week 16, Sitting systolic blood pressure: <90mmHg	1 0.8%	0 0.0%
Up to Week 16, Sitting systolic blood pressure: Change >= 30mmHg increase	2 1.5%	4 2.9%
Up to Week 16, Sitting systolic blood pressure: Change >= 30mmHg decrease	2 1.5%	5 3.7%
Up to Week 48, Pulse rate: <40 bpm	0 0.0%	0 0.0%
Up to Week 48, Pulse rate: >120 bpm	0 0.0%	1 0.7%
Up to Week 48, Sitting diastolic blood pressure: <50 mmHg	0 0.0%	0 0.0%
Up to Week 48, Sitting diastolic blood pressure: Change >= 20mmHg increase	5 3.8%	8 5.9%
Up to Week 48, Sitting diastolic blood pressure: Change >= 20mmHg decrease	11 8.3%	8 5.9%
Up to Week 48, Sitting systolic blood pressure: <90mmHg	1 0.8%	0 0.0%
Up to Week 48, Sitting systolic blood pressure: Change >= 30mmHg increase	5 3.8%	5 3.7%
Up to Week 48, Sitting systolic blood pressure: Change >= 30mmHg decrease	5 3.8%	7 5.1%

7. Secondary Outcome

Title	Number of Participants With Abnormalities in Physical Examination
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.
Time Frame	Screening, Week 16, and Week 48

Outcome Measure Data

Analysis Population Description

Safety analysis set: included all participants who were randomized and received at least one dose of the investigational product (i.e., tofacitinib or placebo). Here, "number analyzed" signifies participants evaluable for this outcome measure for specified rows.

Arm/Group Title		Tofacitinib	Placebo Then Tofacitinib
Arm/Group Description:		Participants received Tofacitinib tablets 5 milligram (mg), twice daily for 48 weeks.	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).
Overall Number of Participants Analyzed		133	136
Measure Type: Count of Participants; Unit of Measure: Participants
Abdomen: Screening	Number Analyzed	133 participants	135 participants
		2 1.5%	1 0.7%
Abdomen: Week 16	Number Analyzed	132 participants	132 participants
		1 0.8%	2 1.5%
Abdomen: Week 48	Number Analyzed	119 participants	119 participants
		1 0.8%	1 0.8%
Extremities: Screening	Number Analyzed	133 participants	136 participants
		17 12.8%	15 11.0%
Extremities: Week 16	Number Analyzed	132 participants	132 participants
		8 6.1%	14 10.6%
Extremities: Week 48	Number Analyzed	119 participants	119 participants
		4 3.4%	7 5.9%
General appearance: Screening	Number Analyzed	133 participants	135 participants
		10 7.5%	11 8.1%
General appearance: Week 16	Number Analyzed	132 participants	132 participants
		9 6.8%	9 6.8%
General appearance: Week 48	Number Analyzed	119 participants	119 participants
		7 5.9%	6 5.0%
Head, eyes, ears, nose, throat: Screening	Number Analyzed	133 participants	135 participants
		5 3.8%	7 5.2%
Head, eyes, ears, nose, throat: Week 16	Number Analyzed	132 participants	132 participants
		4 3.0%	7 5.3%
Head, eyes, ears, nose, throat: Week 48	Number Analyzed	119 participants	119 participants
		3 2.5%	7 5.9%
Heart: Screening	Number Analyzed	133 participants	136 participants
		2 1.5%	2 1.5%
Heart: Week 16	Number Analyzed	132 participants	132 participants
		0 0.0%	2 1.5%
Heart: Week 48	Number Analyzed	119 participants	119 participants
		0 0.0%	2 1.7%
Lungs: Screening	Number Analyzed	133 participants	136 participants
		1 0.8%	0 0.0%
Lungs: Week 16	Number Analyzed	132 participants	132 participants
		0 0.0%	0 0.0%
Lungs: Week 48	Number Analyzed	119 participants	119 participants
		0 0.0%	0 0.0%
Lymph nodes: Screening	Number Analyzed	133 participants	136 participants
		2 1.5%	3 2.2%
Lymph nodes: Week 16	Number Analyzed	132 participants	131 participants
		1 0.8%	2 1.5%
Lymph nodes: Week 48	Number Analyzed	119 participants	119 participants
		1 0.8%	2 1.7%
Neurological: Screening	Number Analyzed	133 participants	135 participants
		4 3.0%	0 0.0%
Neurological: Week 16	Number Analyzed	132 participants	131 participants
		1 0.8%	0 0.0%
Neurological: Week 48	Number Analyzed	119 participants	119 participants
		2 1.7%	0 0.0%
Skin: Screening	Number Analyzed	133 participants	135 participants
		18 13.5%	18 13.3%
Skin: Week 16	Number Analyzed	132 participants	132 participants
		14 10.6%	13 9.8%
Skin: Week 48	Number Analyzed	119 participants	119 participants
		12 10.1%	12 10.1%

8. Secondary Outcome

Title	Number of Participants With Electrocardiogram (ECG) Abnormalities
Description	Twelve-lead electrocardiograms (ECGs) were obtained for all participants. 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.
Time Frame	Baseline up to Week 16, Baseline up to Week 48

Outcome Measure Data

Analysis Population Description

Safety analysis set: included all participants who were randomized and received at least one dose of the investigational product (i.e., tofacitinib or placebo). Here "Overall number of participants analyzed" signifies participants evaluable for this outcome measure and "number analyzed" signifies participants evaluable for this outcome measure for specified rows.

Arm/Group Title		Tofacitinib	Placebo Then Tofacitinib
Arm/Group Description:		Participants received Tofacitinib tablets 5 milligram (mg), twice daily for 48 weeks.	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).
Overall Number of Participants Analyzed		131	133
Measure Type: Count of Participants; Unit of Measure: Participants
Up to Week 16, PR interval: >=300	Number Analyzed	131 participants	131 participants
		0 0.0%	0 0.0%
Up to Week 16, PR interval: %Change>=25/50%	Number Analyzed	131 participants	131 participants
		0 0.0%	1 0.8%
Up to Week 16, QRS duration: >=140	Number Analyzed	131 participants	131 participants
		1 0.8%	1 0.8%
Up to Week 16, QRS duration: %Change>=50%	Number Analyzed	131 participants	131 participants
		0 0.0%	0 0.0%
Up to Week 16, QT interval: >=500	Number Analyzed	131 participants	131 participants
		0 0.0%	0 0.0%
Up to Week 16, QTCB interval: >=450 and <480	Number Analyzed	131 participants	131 participants
		3 2.3%	7 5.3%
Up to Week 16, QTCB interval: >=480 and <500	Number Analyzed	131 participants	131 participants
		0 0.0%	1 0.8%
Up to Week 16, QTCB interval: >=500	Number Analyzed	131 participants	131 participants
		0 0.0%	0 0.0%
Up to Week 16, QTCB interval: change >=30 and <60	Number Analyzed	131 participants	131 participants
		9 6.9%	7 5.3%
Up to Week 16, QTCB interval: change >=60	Number Analyzed	131 participants	131 participants
		0 0.0%	0 0.0%
Up to Week 16, QTCF interval: >=450 and <480	Number Analyzed	131 participants	131 participants
		3 2.3%	4 3.1%
Up to Week 16, QTCF interval: >=480 and <500	Number Analyzed	131 participants	131 participants
		0 0.0%	0 0.0%
Up to Week 16, QTCF interval: >=500	Number Analyzed	131 participants	131 participants
		0 0.0%	0 0.0%
Up to Week 16, QTCF interval: change >=30 and <60	Number Analyzed	131 participants	131 participants
		5 3.8%	3 2.3%
Up to Week 16, QTCF interval: change >=60	Number Analyzed	131 participants	131 participants
		0 0.0%	0 0.0%
Up to Week 48, PR interval: >=300	Number Analyzed	131 participants	133 participants
		0 0.0%	0 0.0%
Up to Week 48, PR interval: %Change>=25/50%	Number Analyzed	131 participants	133 participants
		0 0.0%	1 0.8%
Up to Week 48, QRS duration: >=140	Number Analyzed	131 participants	133 participants
		3 2.3%	1 0.8%
Up to Week 48, QRS duration: %Change>=50%	Number Analyzed	131 participants	133 participants
		0 0.0%	0 0.0%
Up to Week 48, QT interval: >=500	Number Analyzed	131 participants	133 participants
		0 0.0%	1 0.8%
Up to Week 48, QTCB interval: >=450 and <480	Number Analyzed	131 participants	133 participants
		10 7.6%	10 7.5%
Up to Week 48, QTCB interval: >=480 and <500	Number Analyzed	131 participants	133 participants
		1 0.8%	1 0.8%
Up to Week 48, QTCB interval: >=500	Number Analyzed	131 participants	133 participants
		0 0.0%	0 0.0%
Up to Week 48, QTCB interval: change >=30 and <60	Number Analyzed	131 participants	133 participants
		14 10.7%	11 8.3%
Up to Week 48, QTCB interval: change >=60	Number Analyzed	131 participants	133 participants
		1 0.8%	0 0.0%
Up to Week 48, QTCF interval: >=450 and <480	Number Analyzed	131 participants	133 participants
		5 3.8%	5 3.8%
Up to Week 48, QTCF interval: >=480 and <500	Number Analyzed	131 participants	133 participants
		1 0.8%	0 0.0%
Up to Week 48, QTCF interval: >=500	Number Analyzed	131 participants	133 participants
		0 0.0%	0 0.0%
Up to Week 48, QTCF interval: change >=30 and <60	Number Analyzed	131 participants	133 participants
		9 6.9%	7 5.3%
Up to Week 48, QTCF interval: change >=60	Number Analyzed	131 participants	133 participants
		1 0.8%	0 0.0%

9. Secondary Outcome

Title	Percentage of Participants Achieving ASAS20 Response at Weeks 2, 4, 8, 12, 24, 32, 40 and 48
Description	ASAS20 assess 4 domains: PGA of Disease (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; participant's level of ability on scale of 0 [easy] to 10 [impossible], low score= better functional health) and 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 and absolute change of >=1 unit in >=3 domains and no worsening of >=20% and an absolute change of >=1 unit in remaining domain.
Time Frame	Weeks 2, 4, 8, 12, 24, 32, 40 and 48

Outcome Measure Data

Analysis Population Description

FAS: included all participants who were randomized to the study and received at least one dose of the randomized investigational product (i.e., tofacitinib or placebo). Here, on-drug data was used and missing response (MR) was considered to be Non-response (NR) (MR=NR).

Arm/Group Title	Tofacitinib	Placebo Then Tofacitinib
Arm/Group Description:	Participants received Tofacitinib tablets 5 milligram (mg), twice daily for 48 weeks.	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).
Overall Number of Participants Analyzed	133	136
Measure Type: Number; Unit of Measure: Percentage of participants
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

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	Week 2: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0001
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in percentage
	Estimated Value	18.28
	Confidence Interval	(2-Sided) 95%; 9.06 to 27.50
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.70
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	Week 4: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in percentage
	Estimated Value	31.35
	Confidence Interval	(2-Sided) 95%; 20.64 to 42.06
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 5.47
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	Week 8: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in percentage
	Estimated Value	32.24
	Confidence Interval	(2-Sided) 95%; 21.32 to 43.17
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 5.57
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	Week 12: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in percentage
	Estimated Value	34.61
	Confidence Interval	(2-Sided) 95%; 23.63 to 45.58
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 5.60
	Estimation Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	Week 24: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.5360
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in percentage
	Estimated Value	3.65
	Confidence Interval	(2-Sided) 95%; -7.92 to 15.22
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 5.90
	Estimation Comments	[Not Specified]

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	Week 32: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.4971
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in percentage
	Estimated Value	3.83
	Confidence Interval	(2-Sided) 95%; -7.22 to 14.87
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 5.63
	Estimation Comments	[Not Specified]

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	Week 40: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.7792
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in percentage
	Estimated Value	1.58
	Confidence Interval	(2-Sided) 95%; -9.49 to 12.66
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 5.65
	Estimation Comments	[Not Specified]

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	Week 48: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.3685
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in percentage
	Estimated Value	5.22
	Confidence Interval	(2-Sided) 95%; -6.15 to 16.58
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 5.80
	Estimation Comments	[Not Specified]

10. Secondary Outcome

Title	Percentage of Participants Achieving ASAS40 Response at Weeks 2, 4, 8, 12, 24, 32, 40 and 48
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 participant'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.
Time Frame	Weeks 2, 4, 8, 12, 24, 32, 40 and 48

Outcome Measure Data

Analysis Population Description

FAS: included all participants who were randomized to the study and received at least one dose of the randomized investigational product (i.e., tofacitinib or placebo). Here, on-drug data was used and missing response (MR) was considered to be Non-response (NR) (MR=NR).

Arm/Group Title	Tofacitinib	Placebo Then Tofacitinib
Arm/Group Description:	Participants received Tofacitinib tablets 5 milligram (mg), twice daily for 48 weeks.	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).
Overall Number of Participants Analyzed	133	136
Measure Type: Number; Unit of Measure: Percentage of participants
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

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	Week 2: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0548
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in percentage
	Estimated Value	6.12
	Confidence Interval	(2-Sided) 95%; -0.13 to 12.37
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.19
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	Week 4: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in percentage
	Estimated Value	23.43
	Confidence Interval	(2-Sided) 95%; 15.30 to 31.56
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.15
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	Week 8: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in percentage
	Estimated Value	28.56
	Confidence Interval	(2-Sided) 95%; 19.66 to 37.47
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.54
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	Week 12: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in percentage
	Estimated Value	31.18
	Confidence Interval	(2-Sided) 95%; 21.34 to 41.02
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 5.02
	Estimation Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	Week 24: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.2926
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in percentage
	Estimated Value	6.29
	Confidence Interval	(2-Sided) 95%; -5.43 to 18.01
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 5.98
	Estimation Comments	[Not Specified]

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	Week 32: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.2856
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in percentage
	Estimated Value	6.37
	Confidence Interval	(2-Sided) 95%; -5.32 to 18.06
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 5.97
	Estimation Comments	[Not Specified]

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	Week 40: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.1894
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in percentage
	Estimated Value	7.83
	Confidence Interval	(2-Sided) 95%; -3.87 to 19.54
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 5.97
	Estimation Comments	[Not Specified]

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	Week 48: Analysis performed using Normal approximation adjusting for the stratification factor derived from clinical database via CMH approach
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.3544
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in percentage
	Estimated Value	5.59
	Confidence Interval	(2-Sided) 95%; -6.24 to 17.43
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 6.04
	Estimation Comments	[Not Specified]

11. Secondary Outcome

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
Description	ASDAS(CRP) was derived using BASDAI (6-item questionnaire measures disease activity on a scale of 0 [none] to 10 [severe], higher score=more disease activity) and PGA (measure disease activity on a scale of 0 [not active] to 10 [very active], high score=more disease activity) and calculated by using the following formula, 0.121 x Back Pain (Q2 of BASDAI) + 0.058 x Duration of Morning Stiffness (Q6 of BASDAI) + 0.110 x PGA + 0.073 x Peripheral Pain/Swelling (Q3 of BASDAI) + 0.579 x Ln(high sensitivity [hs] CRP mg/Liter [L] + 1). If hsCRP values were smaller than 2 mg/L, they were set to 2 mg/L in the formula. The range of score was >= 0.636 to no defined upper limit. A negative change from baseline value indicates decrease in disease activity; a positive change from baseline value indicates increase in disease activity.
Time Frame	Baseline, Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): included all participants who were randomized to the study and received at least one dose of the randomized investigational product (i.e., tofacitinib or placebo). Here, on-drug data was used and missing response was not imputed. Here "Overall number of participants analyzed" signifies participants evaluable for this outcome measure.

Arm/Group Title	Tofacitinib	Placebo Then Tofacitinib
Arm/Group Description:	Participants received Tofacitinib tablets 5 milligram (mg), twice daily for 48 weeks.	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).
Overall Number of Participants Analyzed	132	136
Least Squares Mean (Standard Error); Unit of Measure: Units on a scale
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)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-0.71
	Confidence Interval	(2-Sided) 95%; -0.85 to -0.57
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.072
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-0.90
	Confidence Interval	(2-Sided) 95%; -1.07 to -0.74
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.083
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-1.06
	Confidence Interval	(2-Sided) 95%; -1.25 to -0.87
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.095
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-1.09
	Confidence Interval	(2-Sided) 95%; -1.28 to -0.90
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.096
	Estimation Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-0.98
	Confidence Interval	(2-Sided) 95%; -1.16 to -0.79
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.093
	Estimation Comments	[Not Specified]

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0623
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-0.19
	Confidence Interval	(2-Sided) 95%; -0.40 to 0.01
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.103
	Estimation Comments	[Not Specified]

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0836
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-0.18
	Confidence Interval	(2-Sided) 95%; -0.39 to 0.02
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.106
	Estimation Comments	[Not Specified]

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0205
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-0.25
	Confidence Interval	(2-Sided) 95%; -0.47 to -0.04
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.108
	Estimation Comments	[Not Specified]

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0614
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-0.20
	Confidence Interval	(2-Sided) 95%; -0.42 to 0.01
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.108
	Estimation Comments	[Not Specified]

12. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

FAS: included all participants who were randomized to the study and received at least one dose of the randomized investigational product (i.e., tofacitinib or placebo). Here, on-drug data was used and missing response was not imputed. Here "Overall number of participants analyzed" signifies participants evaluable for this outcome measure.

Arm/Group Title	Tofacitinib	Placebo Then Tofacitinib
Arm/Group Description:	Participants received Tofacitinib tablets 5 milligram (mg), twice daily for 48 weeks.	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).
Overall Number of Participants Analyzed	132	136
Least Squares Mean (Standard Error); Unit of Measure: Milligrams per deciliter (mg/dL)
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)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-0.93
	Confidence Interval	(2-Sided) 95%; -1.15 to -0.70
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.113
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-0.92
	Confidence Interval	(2-Sided) 95%; -1.16 to -0.68
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.121
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-1.02
	Confidence Interval	(2-Sided) 95%; -1.40 to -0.63
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.196
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-0.96
	Confidence Interval	(2-Sided) 95%; -1.19 to -0.74
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.115
	Estimation Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-0.96
	Confidence Interval	(2-Sided) 95%; -1.20 to -0.72
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.122
	Estimation Comments	[Not Specified]

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.4731
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-0.05
	Confidence Interval	(2-Sided) 95%; -0.20 to 0.09
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.073
	Estimation Comments	[Not Specified]

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.4055
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-0.08
	Confidence Interval	(2-Sided) 95%; -0.26 to 0.11
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.094
	Estimation Comments	[Not Specified]

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.2648
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-0.12
	Confidence Interval	(2-Sided) 95%; -0.34 to 0.09
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.111
	Estimation Comments	[Not Specified]

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.5558
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-0.06
	Confidence Interval	(2-Sided) 95%; -0.25 to 0.14
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.099
	Estimation Comments	[Not Specified]

13. Secondary Outcome

Title	Change From Baseline in Ankylosing Spondylitis Quality of Life (ASQoL) Score at Weeks 16 and 48
Description	The ASQoL was an 18-item questionnaire assessed the amount of restriction participant experienced in daily activities, level of pain and fatigue, and the impact on the participant'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.
Time Frame	Baseline, Weeks 16 and 48

Outcome Measure Data

Analysis Population Description

FAS: included all participants who were randomized to the study and received at least one dose of the randomized investigational product (i.e., tofacitinib or placebo). Here, on-drug data was used and missing response was not imputed. Here "Overall number of participants analyzed" signifies participants evaluable for this outcome measure. Here, "number analyzed" signifies participants evaluable for this outcome measure for specified time point.

Arm/Group Title		Tofacitinib	Placebo Then Tofacitinib
Arm/Group Description:		Participants received Tofacitinib tablets 5 milligram (mg), twice daily for 48 weeks.	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).
Overall Number of Participants Analyzed		129	131
Least Squares Mean (Standard Error); Unit of Measure: Units on scale
Week 16	Number Analyzed	129 participants	130 participants
		-4.03 (0.404)	-2.01 (0.405)
Week 48	Number Analyzed	129 participants	131 participants
		-5.97 (0.454)	-4.70 (0.451)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0001
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-2.02
	Confidence Interval	(2-Sided) 95%; -3.03 to -1.01
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.513
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0270
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-1.26
	Confidence Interval	(2-Sided) 95%; -2.38 to -0.14
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.567
	Estimation Comments	[Not Specified]

14. Secondary Outcome

Title	Change From Baseline in Short-Form-36 Health Survey-Version 2 Acute (SF-36v2) Score at Weeks 16 and 48
Description	SF-36 v.2 (Acute): 36-item generic health status measure. It measured 8 general health domains: physical functioning, role limitations due to physical health, bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional problems, mental health. These domains were aggregated into 2 summary scores - physical component summary (PCS), mental component summary (MCS). Four domains comprised PCS score (physical functioning, role-physical, bodily pain, general health) and remaining 4 domains comprised MCS score (vitality, social functioning, role-emotional, mental health). Normalized domain scores, PCS, MCS scores are used in analyses. Component and domain scores were scored by using United States 1998 general population norm. Resulting norm-based T-scores for both the SF36 version 2 and SF36 health domain scale and component summary measures had means of 50 and standard deviations of 10. Higher PCS/MCS/domain score represent better health status.
Time Frame	Baseline, Weeks 16 and 48

Outcome Measure Data

Analysis Population Description

FAS: included all participants who were randomized to the study and received at least one dose of the randomized investigational product (i.e., tofacitinib or placebo). Here, on-drug data was used and missing response was not imputed. Here "Overall number of participants analyzed" signifies participants evaluable for this outcome measure.

Arm/Group Title	Tofacitinib	Placebo Then Tofacitinib
Arm/Group Description:	Participants received Tofacitinib tablets 5 milligram (mg), twice daily for 48 weeks.	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).
Overall Number of Participants Analyzed	129	130
Least Squares Mean (Standard Error); Unit of Measure: Units on a scale
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)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0088
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	2.22
	Confidence Interval	(2-Sided) 95%; 0.56 to 3.88
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.841
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0016
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	3.00
	Confidence Interval	(2-Sided) 95%; 1.15 to 4.85
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.939
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	4.46
	Confidence Interval	(2-Sided) 95%; 2.69 to 6.23
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.900
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	3.24
	Confidence Interval	(2-Sided) 95%; 1.70 to 4.78
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.781
	Estimation Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	Week 16, Vitality: Analysis performed using ANCOVA model which included fixed effects of treatment group, stratification factor derived from clinical database, and baseline value.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.1065
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	1.78
	Confidence Interval	(2-Sided) 95%; -0.38 to 3.94
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.098
	Estimation Comments	[Not Specified]

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0055
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	2.96
	Confidence Interval	(2-Sided) 95%; 0.88 to 5.05
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.059
	Estimation Comments	[Not Specified]

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.1084
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	2.08
	Confidence Interval	(2-Sided) 95%; -0.46 to 4.61
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.289
	Estimation Comments	[Not Specified]

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.3379
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	1.08
	Confidence Interval	(2-Sided) 95%; -1.13 to 3.29
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.124
	Estimation Comments	[Not Specified]

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	3.55
	Confidence Interval	(2-Sided) 95%; 2.09 to 5.02
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.744
	Estimation Comments	[Not Specified]

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.2529
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	1.33
	Confidence Interval	(2-Sided) 95%; -0.95 to 3.61
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.158
	Estimation Comments	[Not Specified]

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.3744
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	0.86
	Confidence Interval	(2-Sided) 95%; -1.04 to 2.76
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.964
	Estimation Comments	[Not Specified]

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.2091
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	1.36
	Confidence Interval	(2-Sided) 95%; -0.77 to 3.50
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.083
	Estimation Comments	[Not Specified]

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0654
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	2.12
	Confidence Interval	(2-Sided) 95%; -0.14 to 4.38
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.146
	Estimation Comments	[Not Specified]

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.2100
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	1.22
	Confidence Interval	(2-Sided) 95%; -0.69 to 3.12
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.968
	Estimation Comments	[Not Specified]

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.6568
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	0.56
	Confidence Interval	(2-Sided) 95%; -1.90 to 3.01
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.248
	Estimation Comments	[Not Specified]

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.2288
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	1.39
	Confidence Interval	(2-Sided) 95%; -0.88 to 3.66
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.152
	Estimation Comments	[Not Specified]

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.4955
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	0.85
	Confidence Interval	(2-Sided) 95%; -1.61 to 3.32
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.250
	Estimation Comments	[Not Specified]

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.5888
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	0.65
	Confidence Interval	(2-Sided) 95%; -1.71 to 3.01
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.200
	Estimation Comments	[Not Specified]

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.1150
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	1.42
	Confidence Interval	(2-Sided) 95%; -0.35 to 3.18
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.896
	Estimation Comments	[Not Specified]

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.5347
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	0.72
	Confidence Interval	(2-Sided) 95%; -1.56 to 3.00
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.158
	Estimation Comments	[Not Specified]

15. Secondary Outcome

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
Description	BASMI assess axial status and spinal mobility. It composed of 5 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 score mapped between 0 and 10, high score=more impairment of axial status, spinal mobility. For cervical rotation angle, participant sit straight on chair with chin level and hands on knees. Blinded assessor place goniometer at top of head in line with nose and ask participant to rotate neck maximally to left, follows with goniometer and record angle between sagittal plane and new plane after rotation. A second reading obtained and both readings recorded. Procedure repeated for right side. Better of two for each side was selected for scoring. Scoring done by calculating mean of left and right measurement and recorded in degrees (range: 0 to 90), higher cervical rotation value=better health status.
Time Frame	Baseline, Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Outcome Measure Data

Analysis Population Description

FAS: included all participants who were randomized to the study and received at least one dose of the randomized investigational product (i.e., tofacitinib or placebo). Here, on-drug data was used and missing response was not imputed. Here "Overall number of participants analyzed" signifies participants evaluable for this outcome measure.

Arm/Group Title	Tofacitinib	Placebo Then Tofacitinib
Arm/Group Description:	Participants received Tofacitinib tablets 5 milligram (mg), twice daily for 48 weeks.	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).
Overall Number of Participants Analyzed	132	136
Least Squares Mean (Standard Error); Unit of Measure: Degrees
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)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.1513
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	1.29
	Confidence Interval	(2-Sided) 95%; -0.48 to 3.06
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.898
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.1279
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	1.56
	Confidence Interval	(2-Sided) 95%; -0.45 to 3.56
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.020
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0003
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	3.83
	Confidence Interval	(2-Sided) 95%; 1.75 to 5.90
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.056
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0102
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	3.32
	Confidence Interval	(2-Sided) 95%; 0.79 to 5.84
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.282
	Estimation Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0003
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	4.73
	Confidence Interval	(2-Sided) 95%; 2.20 to 7.26
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.285
	Estimation Comments	[Not Specified]

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.8950
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	0.19
	Confidence Interval	(2-Sided) 95%; -2.64 to 3.02
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.439
	Estimation Comments	[Not Specified]

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.4732
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-0.98
	Confidence Interval	(2-Sided) 95%; -3.67 to 1.71
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.365
	Estimation Comments	[Not Specified]

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.6359
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-0.72
	Confidence Interval	(2-Sided) 95%; -3.72 to 2.28
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.523
	Estimation Comments	[Not Specified]

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.6894
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-0.60
	Confidence Interval	(2-Sided) 95%; -3.54 to 2.35
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.495
	Estimation Comments	[Not Specified]

16. Secondary Outcome

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
Description	BASMI assessed axial status and spinal mobility, using linear function. It composed of 5 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, with higher scores indicating more impairment of axial status and spinal mobility. For the assessment of intermalleolar distances, participant should lie supine with the knees straight and feet/toes pointing straight up and asked to separate the legs as far as possible and the distance between the medial malleoli was measured (in Centimeters [cm] to the nearest 0.1 cm). Distance (in cm) was greater than or equal to 0, with no maximum defined range: higher intermalleolar distance value indicates better health status.
Time Frame	Baseline, Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Outcome Measure Data

Analysis Population Description

FAS: included all participants who were randomized to the study and received at least one dose of the randomized investigational product (i.e., tofacitinib or placebo). Here, on-drug data was used and missing response was not imputed. Here "Overall number of participants analyzed" signifies participants evaluable for this outcome measure.

Arm/Group Title	Tofacitinib	Placebo Then Tofacitinib
Arm/Group Description:	Participants received Tofacitinib tablets 5 milligram (mg), twice daily for 48 weeks.	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).
Overall Number of Participants Analyzed	132	136
Least Squares Mean (Standard Error); Unit of Measure: Centimeters
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)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.1410
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	1.39
	Confidence Interval	(2-Sided) 95%; -0.46 to 3.24
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.940
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0122
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	2.78
	Confidence Interval	(2-Sided) 95%; 0.61 to 4.95
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.102
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0085
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	3.32
	Confidence Interval	(2-Sided) 95%; 0.86 to 5.79
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.252
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0184
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	3.36
	Confidence Interval	(2-Sided) 95%; 0.57 to 6.15
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.416
	Estimation Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0026
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	4.19
	Confidence Interval	(2-Sided) 95%; 1.47 to 6.91
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.380
	Estimation Comments	[Not Specified]

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0236
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	3.40
	Confidence Interval	(2-Sided) 95%; 0.46 to 6.35
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.495
	Estimation Comments	[Not Specified]

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0182
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	3.66
	Confidence Interval	(2-Sided) 95%; 0.63 to 6.70
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.541
	Estimation Comments	[Not Specified]

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0133
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	3.85
	Confidence Interval	(2-Sided) 95%; 0.81 to 6.90
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.545
	Estimation Comments	[Not Specified]

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0245
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	3.49
	Confidence Interval	(2-Sided) 95%; 0.45 to 6.52
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.541
	Estimation Comments	[Not Specified]

17. Secondary Outcome

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
Description	BASMI assess axial status, spinal mobility, using linear function. It composed of 5 clinical measures. BASMI - Linear Method score-average of 5 component scores mapped between 0 and 10, with high scores =more impairment of axial status, spinal mobility. For assessment of lateral spinal flexion: participant stand upright with head and back rest against wall as close as possible with shoulders level and feet 30 cm apart and feet parallel. At tip of middle finger, place a mark on thigh. This neutral position recorded. Participant bend sideways without bending knees or lifting heels while attempting to keep shoulders in same position (flexion position). Second mark placed, lateral flexion recorded (left or right as appropriate) using cm tape measure. Two tries for left, two tries for right measured. Result of two tries recorded for left and right separately in cm to nearest 0.1 cm. Distance (in cm) should be >=0, with no maximum defined range: high value indicates better health status.
Time Frame	Baseline, Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Outcome Measure Data

Analysis Population Description

FAS: included all participants who were randomized to the study and received at least one dose of the randomized investigational product (i.e., tofacitinib or placebo). Here, on-drug data was used and missing response was not imputed. Here "Overall number of participants analyzed" signifies participants evaluable for this outcome measure.

Arm/Group Title	Tofacitinib	Placebo Then Tofacitinib
Arm/Group Description:	Participants received Tofacitinib tablets 5 milligram (mg), twice daily for 48 weeks.	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).
Overall Number of Participants Analyzed	132	136
Least Squares Mean (Standard Error); Unit of Measure: Centimeters
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)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0018
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	0.81
	Confidence Interval	(2-Sided) 95%; 0.30 to 1.32
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.257
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0005
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	1.06
	Confidence Interval	(2-Sided) 95%; 0.47 to 1.65
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.301
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0001
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	1.19
	Confidence Interval	(2-Sided) 95%; 0.59 to 1.79
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.305
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	1.63
	Confidence Interval	(2-Sided) 95%; 1.09 to 2.17
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.274
	Estimation Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	1.87
	Confidence Interval	(2-Sided) 95%; 1.20 to 2.55
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.344
	Estimation Comments	[Not Specified]

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0075
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	0.95
	Confidence Interval	(2-Sided) 95%; 0.26 to 1.65
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.353
	Estimation Comments	[Not Specified]

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.1489
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	0.58
	Confidence Interval	(2-Sided) 95%; -0.21 to 1.38
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.403
	Estimation Comments	[Not Specified]

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0609
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	0.78
	Confidence Interval	(2-Sided) 95%; -0.04 to 1.61
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.417
	Estimation Comments	[Not Specified]

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.4822
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	0.30
	Confidence Interval	(2-Sided) 95%; -0.54 to 1.15
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.429
	Estimation Comments	[Not Specified]

18. Secondary Outcome

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
Description	BASMI assessed axial status and spinal mobility. BASMI - Linear Method score was average of 5 individual component scores mapped between 0 and 10, with higher scores indicating more impairment of axial status and spinal mobility. For the assessment of lumbar flexion, With the participant standing erect and outer edges of feet 30 cm apart, a mark was placed in the midpoint of a line that joins the posterior superior iliac spines (baseline mark). A second mark (A) was placed 10 cm above the baseline mark and a third mark (B) 5 cm below the baseline mark. Then have the participant maximally bend forward, keeping the knees fully extended. With the participant's spine in full flexion, the distance between marks A and B (in cm to the nearest 0.1 cm) was re-measured. Distance (in cm) was greater than or equal to 0, with no maximum defined range. Higher value indicates better health status.
Time Frame	Baseline, Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48

Outcome Measure Data

Analysis Population Description

FAS: included all participants who were randomized to the study and received at least one dose of the randomized investigational product (i.e., tofacitinib or placebo). Here, on-drug data was used and missing response was not imputed. Here "Overall number of participants analyzed" signifies participants evaluable for this outcome measure.

Arm/Group Title	Tofacitinib	Placebo Then Tofacitinib
Arm/Group Description:	Participants received Tofacitinib tablets 5 milligram (mg), twice daily for 48 weeks.	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).
Overall Number of Participants Analyzed	132	136
Least Squares Mean (Standard Error); Unit of Measure: Centimeters
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)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0047
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	0.37
	Confidence Interval	(2-Sided) 95%; 0.12 to 0.63
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.131
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0001
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	0.52
	Confidence Interval	(2-Sided) 95%; 0.26 to 0.77
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.131
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib, Placebo Then Tofacitinib
	Comments	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.