Safety and Efficacy of Pf-06650833 In Subjects With Rheumatoid Arthritis, With An Inadequate Response To Methotrexate

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02996500
• Collaborator: (none)
• Enrollment: 269
• Locations: 103
• Arms: 6
• Actual Duration (Months): 21.1
• Patients Per Site: 2.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is a Phase 2, multicenter, randomized, double blind, double dummy, placebo and active-controlled, parallel group study to assess the efficacy and safety of PF 06650833 at Week 12 in subjects with moderate-severe, active, RA who have had an inadequate response to MTX. PF-06650833 or matching placebo tablets will be administered orally QD under fasting conditions, and tofacitinib or matching tofacitinib placebo tablets will be administered orally BID for 12 weeks in a blinded fashion.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Drug: PF-06650833; Drug: Placebo; Drug: Tofacitinib	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 269 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A 12 WEEK RANDOMIZED, DOUBLE-BLIND, DOUBLE DUMMY, PARALLEL GROUP, ACTIVE AND PLACEBO-CONTROLLED, MULTICENTER STUDY TO ASSESS THE EFFICACY AND SAFETY PROFILE OF PF-06650833 IN SUBJECTS WITH ACTIVE RHEUMATOID ARTHRITIS WITH AN INADEQUATE RESPONSE TO METHOTREXATE
• Actual Study Start Date: Nov 10, 2016
• Actual Primary Completion Date: Aug 15, 2018
• Actual Study Completion Date: Aug 15, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm 1: 20 mg QD PF-06650833 , 20 mg QD	Drug: PF-06650833; Investigational
Experimental: Arm 2: 60 mg QD PF-06650833, 60 mg QD	Drug: PF-06650833; Investigational
Experimental: Arm 3: 200 mg QD Pf-06650833, 200 mg QD	Drug: PF-06650833; Investigational
Experimental: Arm 4: 400 mg QD PF-06650833, 400 mg QD	Drug: PF-06650833; Investigational
Placebo Comparator: Placebo Placebo, 0 mg BID	Drug: Placebo; Placebo
Active Comparator: Arm 5: Tofacitinib Tofacitinib 5 mg BID	Drug: Tofacitinib; Investigational; Other Names: Xeljanz

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in the Simplified Disease Activity Index (SDAI) at Week 12 [Baseline and Week 12]

   The SDAI is a continuous composite measure derived from components of the American College of Rheumatology (ACR) Core Dataset.The SDAI was calculated using the following formula: SDAI = Tender / Painful Joint Count(TJC) (using 28 joints) + Swollen Joint Count (SJC) (using 28 joints) + Patient Global Assessment of Arthritis (PtGA) (0-10 cm scale) + Physician's Global Assessment of Arthritis (PhGA) (0-10 cm scale) + high sensitivity C-reactive protein (hsCRP) (mg/dL). SDAI total score= 0-86. SDAI <=3.3 indicates disease remission, >3.4 to 11 = low disease activity, >11 to 26 = moderate disease activity, and >26 = high disease activity. The primary analysis utilized a Bayesian ANCOVA model with an informative placebo prior distribution with borrowing from tofacitinib historical placebo data. The confidence interval was credible interval in this statistical analysis. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.

Secondary Outcome Measures

1. Change From Baseline in SDAI at Weeks 4 and 8 [Baseline, Weeks 4 and 8]

   The SDAI is a continuous composite measure derived from components of the American College of Rheumatology (ACR) Core Dataset.The SDAI was calculated using the following formula: SDAI = TJC (using 28 joints) + SJC (using 28 joints) + PtGA (0-10 cm scale) + PhGA (0-10 cm scale) + hsCRP (mg/dL). SDAI total score= 0-86. SDAI <=3.3 indicates disease remission, >3.4 to 11 = low disease activity, >11 to 26 = moderate disease activity, and >26 = high disease activity. The descriptive summary of change from baseline in SDAI was based on a mixed effect model repeat measurement MMRM model with observed data. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.

2. Percentage of Participants With SDAI Low Disease Activity Score (LDAS) (SDAI <=11) at 4, 8, and 12 Weeks [Weeks 4, 8 and 12]

   The SDAI is a continuous composite measure derived from components of the American College of Rheumatology (ACR) Core Dataset.The SDAI was calculated using the following formula: SDAI = TJC (using 28 joints) + SJC (using 28 joints) + PtGA (0-10 cm scale) + PhGA (0-10 cm scale) + hsCRP (mg/dL). The criterion of SDAI LDAS was SDAI<=11. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.

3. Percentage of Participants With SDAI Remission (SDAI <=3.3) at 4, 8, and 12 Weeks [Weeks 4, 8 and 12]

   The SDAI is a continuous composite measure derived from components of the American College of Rheumatology (ACR) Core Dataset.The SDAI was calculated using the following formula: SDAI = TJC (using 28 joints) + SJC (using 28 joints) + PtGA (0-10 cm scale) + PhGA (0-10 cm scale) + hsCRP (mg/dL). The criterion of SDAI remission was SDAI<=3.3. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.

4. Percentage of Participants With Disease Activity Score-28 (4 Components Based on Erythrocyte Sedimentation Rate) (DAS28-4 [ESR]) LDAS (DAS28 <3.2) at 4, 8, and 12 Weeks [Weeks 4, 8 and 12]

   The DAS assessment is a continuous composite measure derived using differential weighting given to each component. The components of the DAS28-4 (ESR) assessment included: tender joint count with 28 joints assessed, swollen joint count with 28 joints assessed, ESR and PGA. DAS28-4 (ESR) was calculated as 0.56 sqrt (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.70 ln(ESR [mm/first hour] + 0.014 (PtGA [mm]). Total score range: 0-9.4. Higher score indicated more disease activity. The criterion of DAS28-4 (ESR) LDAS was DAS28<3.2. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.

5. Percentage of Participants With DAS28-3 (ESR) LDAS (DAS28 <3.2) at 4, 8, and 12 Weeks [Weeks 4, 8 and 12]

   The DAS assessment is a continuous composite measure derived using differential weighting given to each component. The components of the DAS28-3 (ESR) assessment included: tender joint count with 28 joints assessed, swollen joint count with 28 joints assessed and ESR. DAS28-3 (ESR) was calculated as 0.56 sqrt (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.70 ln(ESR [mm/first hour]*1.08+0.16. Total score range: 0-9.4. Higher score indicated more disease activity. The criterion of DAS28-3 LDAS was DAS28<3.2. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.

6. Percentage of Participants With Disease Activity Score-28 (4 Components Based on High-Sensitivity C-Reactive Protein) (DAS28-4 [CRP]) LDAS (DAS28 <3.2) at 4, 8, and 12 Weeks [Weeks 4, 8 and 12]

   The DAS assessment is a continuous composite measure derived using differential weighting given to each component. The components of the DAS28-4 (CRP) assessment included: tender joint count with 28 joints assessed, swollen joint count with 28 joints assessed, hs-CRP and PtGA. DAS28-4 (CRP) was calculated as 0.56 sqrt (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.36 ln(CRP [mg/L] +1) + 0.014 (PtGA [mm]) + 0.96. Total score range: 0-9.4. Higher score indicated more disease activity. The criterion of DAS28-4 LDAS was DAS28<3.2. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.

7. Percentage of Participants With DAS28-3 (CRP) LDAS (DAS28 <3.2) at 4, 8, and 12 Weeks [Weeks 4, 8 and 12]

   The DAS assessment is a continuous composite measure derived using differential weighting given to each component. The components of the DAS28-3 (CRP) assessment included: tender joint count with 28 joints assessed, swollen joint count with 28 joints assessed and hs-CRP. DAS28-3 (CRP) was calculated as 0.56 sqrt (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.36 ln(CRP [mg/L] +1)*1.10+ 1.15. Total score range: 0-9.4. Higher score indicated more disease activity. The criterion of DAS28-3 LDAS was DAS28<3.2. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.

8. Percentage of Participants With DAS28-4 (ESR) Remission (DAS28 <2.6) at 4, 8 and 12 Weeks [Weeks 4, 8 and 12]

   The DAS assessment is a continuous composite measure derived using differential weighting given to each component. The components of the DAS28-4 (ESR) assessment included: tender joint count with 28 joints assessed, swollen joint count with 28 joints assessed, ESR and PtGA. DAS28-4 (ESR) was calculated as 0.56 sqrt (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.70 ln(ESR [mm/first hour] + 0.014 (PtGA [mm]). Total score range: 0-9.4. Higher score indicated more disease activity. The criterion of DAS28-4 remission was DAS28<2.6. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.

9. Percentage of Participants With DAS28-3 (ESR) Remission (DAS28 <2.6) at 4, 8 and 12 Weeks [Weeks 4, 8 and 12]

   The DAS assessment is a continuous composite measure derived using differential weighting given to each component. The components of the DAS28-3 (ESR) assessment included: tender joint count with 28 joints assessed, swollen joint count with 28 joints assessed and ESR. DAS28-3 (ESR) was calculated as 0.56 sqrt (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.70 ln(ESR [mm/first hour]*1.08+0.16. Total score range: 0-9.4. Higher score indicated more disease activity. The criterion of DAS28-3 remission was DAS28<2.6. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.

10. Percentage of Participants With DAS28-4 (CRP) Remission (DAS28 <2.6) at 4, 8 and 12 Weeks [Weeks 4, 8 and 12]

    The DAS assessment is a continuous composite measure derived using differential weighting given to each component. The components of the DAS28-4 (CRP) assessment included: tender joint count with 28 joints assessed, swollen joint count with 28 joints assessed, hs-CRP and PtGA. DAS28-4 (CRP) was calculated as 0.56 sqrt (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.36 ln(CRP [mg/L] +1) + 0.014 (PtGA [mm]) + 0.96. Total score range: 0-9.4. Higher score indicated more disease activity. The criterion of DAS28-4 remission was DAS28<2.6. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.

11. Percentage of Participants With DAS28-3 (CRP) Remission (DAS28 <2.6) at 4, 8 and 12 Weeks [Weeks 4, 8 and 12]

    The DAS assessment is a continuous composite measure derived using differential weighting given to each component. The components of the DAS28-3 (CRP) assessment included: tender joint count with 28 joints assessed, swollen joint count with 28 joints assessed and hs-CRP. DAS28-3 (CRP) was calculated as 0.56 sqrt (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.36 ln(CRP [mg/L] +1)*1.10+1.15. Total score range: 0-9.4. Higher score indicated more disease activity. The criterion of DAS28-3 remission was DAS28<2.6. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.

12. Change From Baseline in DAS28-4 (ESR) at 4, 8 and 12 Weeks [Baseline, Weeks 4, 8 and 12]

    The DAS assessment is a continuous composite measure derived using differential weighting given to each component. The components of the DAS28-4 (ESR) assessment included: tender joint count with 28 joints assessed, swollen joint count with 28 joints assessed, ESR and PtGA. DAS28-4 (ESR) was calculated as 0.56 sqrt (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.70 ln(ESR [mm/first hour] + 0.014 (PtGA [mm]). Higher score indicated more disease activity. Total score range: 0-9.4. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.

13. Change From Baseline in DAS28-3 (ESR) at 4, 8 and 12 Weeks [Baseline, Weeks 4, 8 and 12]

    The DAS assessment is a continuous composite measure derived using differential weighting given to each component. The components of the DAS28-3 (ESR) assessment included: tender joint count with 28 joints assessed, swollen joint count with 28 joints assessed and ESR. DAS28-3 (ESR) was calculated as 0.56 sqrt (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.70 ln(ESR) [mm/first hour]*1.08+0.16. Total score range: 0-9.4. Higher score indicated more disease activity. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.

14. Change From Baseline in DAS28-4 (CRP) at 4, 8 and 12 Weeks [Baseline, Weeks 4, 8 and 12]

    The DAS assessment is a continuous composite measure derived using differential weighting given to each component. The components of the DAS28-4 (CRP) assessment included: tender joint count with 28 joints assessed, swollen joint count with 28 joints assessed, hs-CRP and PtGA. DAS28-4 (CRP) was calculated as 0.56 sqrt (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.36 ln(CRP [mg/L] +1) + 0.014 (PtGA [mm]) + 0.96. Total score range: 0-9.4. Higher score indicated more disease activity. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.

15. Change From Baseline in DAS28-3 (CRP) at 4, 8 and 12 Weeks [Baseline, Weeks 4, 8 and 12]

    The DAS assessment is a continuous composite measure derived using differential weighting given to each component. The components of the DAS28-3 (CRP) assessment included: tender joint count with 28 joints assessed, swollen joint count with 28 joints assessed and hs-CRP. DAS28-3 (CRP) was calculated as 0.56 sqrt (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.36 ln(CRP [mg/L] +1)*1.10+ 1.15. Total score range: 0-9.4. Higher score indicated more disease activity. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.

16. Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at 4, 8 and 12 Weeks [Weeks 4, 8 and 12]

    ACR20 was calculated as a 20% improvement in TJC and SJC and 20% improvement in 3 of the 5 remaining ACR core set measures: PtGA and PhGA, pain, disability, and an acute phase reactant which for this study was CRP or ESR. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.

17. Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response at 4, 8 and 12 Weeks [Weeks 4, 8 and 12]

    ACR50 was calculated as a 50% improvement in TJC and SJC and 50% improvement in 3 of the 5 remaining ACR core set measures: PtGA and PhGA, pain, disability, and an acute phase reactant which for this study was CRP or ESR. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.

18. Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response at 4, 8 and 12 Weeks [Weeks 4, 8 and 12]

    ACR70 was calculated as a 70% improvement in TJC and SJC and 70% improvement in 3 of the 5 remaining ACR core set measures: PtGA and PhGA, pain, disability, and an acute phase reactant which for this study was CRP or ESR. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.

19. Change From Baseline in the Tender/Painful and Swollen Joint Counts at 4, 8 and 12 Weeks [Baseline, Weeks 4, 8 and 12]

    The TJC (28) included the following joints: shoulders, elbows, wrists, metatarsophalangeal (MCP) joints, PIP joints, and knees. This count was calculated from the TJC (68) assessed. The SJC (28) included the same joints as TJC (28), and was calculated from the SJC 66 assessed for swelling.Sixty eight (68) joints were assessed by a blinded joint assessor to determine the number of joints that were considered tender or painful. The 68 joints assessed were: temporomandibular, sternoclavicular, acromioclavicular; shoulder, elbow, wrist, MCPs, thumb interphalangeal, proximal interphalangeals, and distal interphalangeals; hip, knee, ankle, tarsus, metatarsophalangeals, great toe interphalangeal, proximal and distal interphalangeals combined. Sixty-six (66) joints were assessed for swelling, the same as those listed for TJC, excluding the right and left hip joints. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.

20. Change From Baseline in High-Sensitivity C-Reactive Protein (Hs-CRP) at 4, 8 and 12 Weeks [Baseline, Weeks 4, 8 and 12]

    Serum samples were analyzed to determine the level of hs-CRP, which was an acute-phase reactant. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.

21. Change From Baseline in the Physician's Global Assessment of Arthritis (PhGA) at 4, 8, and 12 Weeks [Baseline, Weeks 4, 8 and 12]

    The investigator assessed how the participant's overall arthritis appeared at the time of the visit. This was an evaluation based on the participant's disease symptoms, functional capacity and physical examination, and was independent of the participant's reported assessments of PtGA (patient's global assessment of arthritis). The investigator's response was recorded using a 100 mm visual analog scale (VAS), with the 0 mm end labeled "None" and the 100 mm end labeled "Extreme". Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.

22. Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Treatment-Related TEAEs [Baseline up to 28 calendar days after the last administration of the investigational product (about 21 months)]

    AE was defined as any untoward medical occurrence in a clinical investigation participant administered a product or medical device, regardless of the causal relationship to study treatment. Treatment-emergent AEs (TEAEs) were defined as AEs which occurred for the first time during the effective duration of treatment or AEs that increased in severity during treatment. Serious AEs (SAEs) were defined as any untoward medical occurrence at any dose that resulted in death; was life-threatening (immediate risk of death); required inpatient hospitalization or caused prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduction normal life functions). AEs included SAEs and non-serious AEs. Causality to study treatment was determined by the investigator.

23. Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) [Baseline up to 28 calendar days after the last administration of the investigational product (about 21 months)]

    Laboratory evaluation included hematology, clinical chemistry, and urinalysis. Laboratory parameters included: hematology (hemoglobin, hematocrit, red blood cell, platelet and white blood cell count, neutrophils, eosinophils, monocytes, basophils and lymphocytes), chemistry (blood urea nitrogen, creatinine, sodium, potassium, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, albumin, total protein and serum pregnancy test [for all female participants]) and urine (urine pregnancy test [for all female participants]). Each parameter was evaluated against commonly used and widely accepted criteria. Clinical significance of laboratory parameters was determined at the investigator's discretion. The investigator judged the abnormality.

24. Number of Participants With Vital Signs Data Meeting Pre-sepcified Criteria [Baseline up to 28 calendar days after the last administration of the investigational product (about 21 months)]

    Vital Signs tests included sitting systolic blood pressure (SBP) and diastolic blood pressure (DBP) and pulse rate. Vital signs categorical summarization criteria were 1), systolic BP (SBP) <90 millimeters of mercury (mm Hg) or change from baseline (Chg) >=30mm Hg; diastolic BP (DBP) <50mm Hg or change from baseline >=20mm Hg; 2), pulse rate <40bpm or > 120bpm.

25. Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-sepcified Criteria [Baseline up to 28 calendar days after the last administration of the investigational product (about 21 months)]

    ECG evaluation included: PR interval, time from ECG Q wave to the end of the S wave corresponding to ventricle depolarization (QRS interval), time between the start of the Q wave and the end of the T wave in the heart's electrical cycle (QT interval), QT interval corrected for heart rate using Fridericia's formula (QTcF interval), and QTc calculated using Bazett's correction factor (QTcB interval).

26. Number of Participants With Urinalysis Data Meeting Pre-specified Criteria [Baseline up to 28 calendar days after the last administration of the investigational product (about 21 months)]

    The urine sample was collected for central laboratory urinalysis and urine microscopy. The urinalysis included pH, protein, glucose, erythrocytes, leukocytes, ketones, nitrite, urobilinogen, urine bilirubin, urine hemoglobin, leukocyte esterase, granular casts, hyaline casts, bacteria, atypical, needle-like crystals urine, specific gravity, microscopy and urine albumin test.

27. Change From Baseline in the Patient's Assessment of Arthritis Pain (PAAP) Visual Analogue Scale (VAS) at Weeks 4, 8, 12 [Baseline, Weeks 4, 8 and 12]

    Patients assess the severity of their arthritis pain using a 100 mm VAS by placing a mark on the scale between 0 (no pain) and 100 (most severe pain), which corresponds to the magnitude of their pain. This assessment was performed early in the clinic visit and before the participant had extensive contact with site personnel and/or Investigator. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.

28. Change From Baseline in the Patient Global Assessment of Arthritis (PtGA) VAS at Weeks 4, 8, 12 [Baseline, Weeks 4, 8 and 12]

    Patients answer the following question: "Considering all the ways your arthritis affects you, how are you feeling today?" The patient's response is recorded using a 100 mm VAS. This assessment was performed early in the clinic visit and before the participant had extensive contact with site personnel and/or Investigator. The higher score indicated more severe disease. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.

29. Change From Baseline in the Health Assessment Questionnaire - Disability Index (HAQ-DI) at Weeks 4, 8, and 12 [Baseline, Weeks 4, 8 and 12]

    The HAQ-DI was defined as participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.

30. Change From Baseline in the 36 Item Short Form Health Survey (SF-36) Version 2 (Acute) 8 Domain Scores at Week 12 [Baseline and Week 12]

    The SF-36 version 2 (acute) is a 36 item generic health status measure. It measures 8 general health domains: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional and mental health. The SF-36 summary scores range from 0-100, with higher scores representing better self-reported health. This was performed early in the clinic visit and before the participant had extensive contact with site personnel and/or Investigator. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.

31. Change From Baseline in the Physical Component Score (PCS) and Mental Component Score (MCS) at Week 12 [Baseline and Week 12]

    The SF 36 version 2 (acute) is a 36 item generic health status measure. It measures 8 general health domains. These domains can also be summarized as physical component score (PCS) and mental component score (MCS). The PCS and MCS summary scores range from 0-100, with higher scores representing better self-reported health. The lower the score the more disability. This was performed early in the clinic visit and before the participant had extensive contact with site personnel and/or Investigator. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.

32. Change From Baseline in the European Quality of Life 5 Dimensions-3 Level (EQ-5D-3L) Score at Week 12 [Baseline and Week 12]

    The EQ-5D-3L health state profile is a patient completed questionnaire designed to assess impact on health related quality of life in 5 domains: mobility, self care, usual activities, pain/discomfort, and anxiety/depression. Additionally, scores from the 5 domains might have been used to calculate a single index value, also known as a utility score. The validity and reliability of the EQ-5D-3L have been established in a number of disease states, including RA. EQ-5D-3L scores marked health status from 0 and 100. There were notes at the both ends of the scale that the bottom rate (0) corresponded to " the worst health you could imagine", and the highest rate (100) corresponded to "the best health you could imagine". Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.

33. Change From Baseline in the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Total Score at Week 12 [Baseline and Week 12]

    The FACIT-F is a patient completed questionnaire consisting of 13 items that assess fatigue. Instrument scoring yields a range from 0 to 52, with higher scores representing better patient status (less fatigue). This questionnaire was performed early in the clinic visit and before the participant had extensive contact with site personnel and/or investigator. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Male and female (including WOCBP) subjects between the ages of 18 and 75 years, inclusive.

2. Diagnosis of RA and meeting the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for RA with a Total Score ≥6/10.

3. The subject has active disease at both Screening and Baseline, as defined by both:

• 6 joints tender or painful on motion, AND

• 6 joints swollen; and fulfills 1 of the following 2 criteria at Screening:

• High sensitivity C reactive protein (hsCRP) >7 mg/L at screening

• Erythrocyte sedimentation rate (ESR) (Westergren method) >28 mm/hr;

1. Meets Class I, II or III of the ACR 1991 Revised Criteria for Global Functional Status in RA.

2. Subjects must be ACPA positive between screening and randomization.

3. Subjects must have been taking oral MTX for at least 3 months at an adequate dose to determine that the subject had an inadequate response to MTX

4. Up to 50 % of subjects may have received one (and only one) approved TNF-inhibiting biologic agent administered that was inadequately effective and/or not tolerated. The anti-TNF biologic could also have been discontinued due to lack of continued access.

Exclusion Criteria:

1. Subjects with a known immunodeficiency disorder or a first degree relative with a hereditary immunodeficiency.

2. Subjects with any of the following infections or infections history:

3. Any infection requiring treatment within 2 weeks prior to screening (Visit 1).

4. Any infection requiring hospitalization, parenteral antimicrobial therapy within 60 days, or as otherwise judged to be an opportunistic infection or clinically significant by the investigator, within the past 6 months.

5. Infected joint prosthesis at any time with the prosthesis still in situ.

6. Recurrent (more than one episode) herpes zoster or disseminated (a single episode) herpes zoster or disseminated (a single episode) herpes simplex.

7. Subjects will be screened for HIV. Subjects who test positive for HIV will be excluded from the study.

8. Subjects will be screened for hepatitis B virus infection and will be excluded if positive for hepatitis B surface antigen (HBsAg). Subjects with HBsAg negative testing but who test positive for hepatitis B core antibody (HBcAb) must have further testing for hepatitis B surface antibody (HBsAb). If HBsAb is negative, the subject will be excluded from the study.

9. Subjects with clinically significant active hepatic disease or hepatic impairment by laboratory assessment.

10. Subjects will be screened for hepatitis C virus (HCV Ab). Subjects with positive HCV Ab tests will be reflex tested for HCV ribonucleic acid (HCV RNA). Only subjects with negative HCV Ab or HCV RNA will be allowed to enroll in the study.

11. Evidence of active or latent, untreated or inadequately treated infection with Mycobacterium tuberculosis (TB)

12. Pre-existing chronic autoimmune disease.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinical and Translational Research Center of Alabama, PC	Tuscaloosa	Alabama	United States	35406
2	Dory Hardy, PharmD	Tucson	Arizona	United States	85723
3	Southern Arizona VA Health care System	Tucson	Arizona	United States	85723
4	Robert W. Levin, MD,PA	Clearwater	Florida	United States	33765
5	Millennium Research	Ormond Beach	Florida	United States	32174
6	Arthritis & Rheumatic Care Center	South Miami	Florida	United States	33143
7	Qps-Mra, Llc	South Miami	Florida	United States	33143
8	Medical Associates of North Georgia	Canton	Georgia	United States	30115
9	Graves Gilbert Clinic	Bowling Green	Kentucky	United States	42101
10	Arthritis and Diabetes Clinic, Inc.	Monroe	Louisiana	United States	71203
11	Ramesh C Gupta, M.D.	Memphis	Tennessee	United States	38119
12	Accurate Clinical Management, LLC	Baytown	Texas	United States	77521
13	Accurate Clinical Management, LLC	Houston	Texas	United States	77004
14	Accurate Clinical Management, LLC	Houston	Texas	United States	77084
15	DM Clinical Research	Tomball	Texas	United States	77375
16	Canberra Hospital	Garran	Australian Capital Territory	Australia	2605
17	Genesis Research Services	Broadmeadow	New South Wales	Australia	2292
18	General Hospital "Prim.dr.Abdulah Nakas"	Sarajevo	Kanton Sarajevo	Bosnia and Herzegovina	71000
19	University Clinical Center Republic of Srpska	Banja Luka	Republika Srpska	Bosnia and Herzegovina	78000
20	Health Center Gradiska	Gradiska	Republika Srpska	Bosnia and Herzegovina	78400
21	UMHAT Kaspela	Plovdiv		Bulgaria	4001
22	MHAT Liulin	Sofia		Bulgaria	1336
23	UMHAT "Sv.Ivan Rilski", Clinic of rheumatology	Sofia		Bulgaria	1612
24	Medical Center Synexus Sofia EOOD	Sofia		Bulgaria	1784
25	Specialized Hospital for Active Treatment of Oncology Diseases EAD, Department of Imaging Diagnostic	Sofia		Bulgaria	1784
26	Poliklinika K-centar	Zagreb	GRAD Zagreb	Croatia	10000
27	Medicinski centar Kuna&Peric	Zagreb		Croatia	10000
28	CCBR Ostrava s.r.o.	Ostrava		Czechia	702 00
29	Revmatologicka ambulance	Praha		Czechia	140 00
30	Medical Plus s.r.o.	Uherske Hradiste		Czechia	68601
31	LTD Israeli-Georgian Medical Research Clinic HELSICORE	Tbilisi		Georgia	0112
32	LTD " Diagnostic Service "	Tbilisi		Georgia	0159
33	Ltd Institute of Clinical Cardiology	Tbilisi		Georgia	0159
34	LTD Unimedi Kakheti	Tbilisi		Georgia	0159
35	LTD "MediClubGeorgia"	Tbilisi		Georgia	0160
36	Ltd "Medicore"	Tbilisi		Georgia	0186
37	Unimedi Kakheti LTD	Telavi		Georgia	2200
38	Knappschaftsklinikum Saar GmbH	Puettlingen		Germany	66346
39	Revita Reumatologiai Rendelo	Budapest		Hungary	1027
40	Pest Megyei Flor Ferenc Korhaz	Kistarcsa		Hungary	2143
41	CRU Hungary Ltd.	Miskolc		Hungary	3529
42	Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont	Szeged		Hungary	6725
43	Csongrad Megyei Dr. Bugyi Istvan Korhaz, Mozgasszervi Rehabilitacios Osztaly	Szentes		Hungary	6600
44	VITAL MEDICAL CENTER Orvosi es Fogorvosi Kozpont	Veszprem		Hungary	8200
45	Seoul National University hospital	Seoul		Korea, Republic of	03080
46	Hanyang University Seoul hospital	Seoul		Korea, Republic of	04763
47	Konkuk University Medical Center	Seoul		Korea, Republic of	05030
48	The Catholic University of Korea, Seoul St.Mary's Hospital	Seoul		Korea, Republic of	06591
49	Private Practice - Dr. Miguel Cortes Hernandez	Cuernavaca	Morelos	Mexico	62290
50	Centro Peninsular de Investigacion Clinica S.C.P	Merida	Yucatan	Mexico	97000
51	Kohler & Milstein Research S.A de C.V	Merida	Yucatan	Mexico	97070
52	Centro de Alta Especialidad en Reumatología e Investigación del Potosi, S.C.	San Luis Potosí		Mexico	78213
53	Szpital Specjalistyczny nr 1 w Bytomiu	Bytom		Poland	41-902
54	Synexus Polska Sp. z o.o. Oddzial w Gdansku	Gdansk		Poland	80-382
55	Synexus Polska Sp z o.o. Oddzial w Gdyni	Gdynia		Poland	81-537
56	McBk S.C.	Grodzisk Mazowiecki		Poland	05-825
57	Synexus Polska Sp.Zo.o.	Katowice		Poland	40-040
58	Prywatna Praktyka Lekarska Prof. UM Dr hab. Med. Pawel Hrycaj	Poznan		Poland	61-397
59	Synexus Polska Sp. z o.o.	Warszawa		Poland	01-192
60	Reumatika Centrum Reumatologii NZOZ	Warszawa		Poland	02-691
61	Synexus Polska Sp. z o.o. Oddział we Wroclawiu	Wroclaw		Poland	50-381
62	Centrul Medical Unirea	Bucuresti		Romania	010306
63	Med Life	Bucuresti		Romania	010719
64	Centrul Medical Sana	Bucuresti		Romania	011025
65	Euroclinic Hospital	Bucuresti		Romania	014461
66	Spitalul Clinic de Recuperare Iasi	Iasi		Romania	700661
67	Spitalul Clinic Judetean de Urgenta Tirgu Mures	Tirgu Mures		Romania	540136
68	FSBEI HE "Kazan State Medical University" MoH of RF	Kazan		Russian Federation	420064
69	FSBEI HE "Kazan State Medical University" MoH of RF	Kazan		Russian Federation	420103
70	FSBSI "Scientific Research Institute of Rheumatology n.a. V.A. Nasonova"	Moscow		Russian Federation	115522
71	SBHI of Moscow City Clinical Hospital # 1 n.a. N.I. Pirogov of Moscow Healthcare Department	Moscow		Russian Federation	119049
72	FSBHI Central Clinical Hospital of Russian Academy of Sciences	Moscow		Russian Federation	119333
73	State Budgetary Institution of Ryazan Region "Regional clinical cardiology dispensary"	Ryazan		Russian Federation	390026
74	LLC "Sanavita"	Saint-Petersburg		Russian Federation	190031
75	LLC "Sanavita"	Saint-Petersburg		Russian Federation	195257
76	Saint Petersburg State Budgetary Institution of Health Care "Clinical Rheumatology Hospital #25"	St. Petersburg		Russian Federation	190068
77	SBHI of VR "Regional Clinical Hospital"	Vladimir		Russian Federation	600023
78	Institute of Rheumatology	Belgrade		Serbia	11000
79	Military Medical Academy	Belgrade		Serbia	11000
80	Institute for Treatment and Rehabilitation "Niska Banja"	Niska Banja		Serbia	18205
81	Special Hospital for Rheumatic Diseases Novi Sad	Novi Sad		Serbia	21112
82	Reumacentrum s.r.o.	Partizanske	Trenciansky Kraj.	Slovakia	958 01
83	AAGS s.r.o., Reumatologicka ambulancia	Dunajska Streda		Slovakia	92901
84	Nemocnica Kosice-Saca, a.s.1.sukromna nemocnica	Kosice-Saca		Slovakia	040 15
85	Neštátna Reumatologická ambulancia	Považská Bystrica		Slovakia	017 01
86	REUMEX s.r.o. Reumatologicka ambulancia	Rimavska Sobota		Slovakia	979 01
87	Reumatologicka ambulancia, MUDr. Pavol Polak s.r.o.	Zilina		Slovakia	010 01
88	Complejo Hospitalario Universitario de Santiago de Compostela	Santiago de Compostela	A Coruna	Spain	15706
89	HM Hospital Nuestra Señora de La Esperanza	Santiago de Compostela	A Coruña	Spain	15705
90	Hospital Universitario Cruces	Barakaldo	Vizcaya	Spain	48903
91	Hospital Universitario A Coruña	A Coruña		Spain	15006
92	Hospital Quironsalud Infanta Luisa	Sevilla		Spain	41010
93	China Medical University Hospital	Taichung		Taiwan	40447
94	National Taiwan University Hospital	Taipei		Taiwan	10043
95	Taipei Medical University Hospital	Taipei		Taiwan	110
96	Komunalnyi likuvalno-profilaktychnyi zaklad "Chernihivska oblasna likarnia",	Chernihiv		Ukraine	14029
97	Derzhavna ustanova "Natsionalnyi instytut terapii imeni L.T. Maloi	Kharkiv		Ukraine	61039
98	Komunalne nekomertsiine pidpryiemstvo "Konsultatyvno-diahnostychnyi tsentr"	Kyiv		Ukraine	01103
99	Medychnyi tsentr tovarystva z obmezhenoiu vidpovidalnistiu "Revmotsentr", m. Kyiv	Kyiv		Ukraine	04070
100	Derzhavna ustanova "Instytut herontolohii imeni D.F. Chebotarova	Kyiv		Ukraine	04114
101	Poltavska oblasna klinichna likarnia im. M.V. Sklifosovskoho,	Poltava		Ukraine	36011
102	Ternopilska universytetska likarnia, revmatolohichne viddilennia, Derzhavnyi vyshchyi navchalnyi	Ternopil		Ukraine	46002
103	Vinnytska oblasna klinichna likarnia im. M.I.Pyrohova, revmatolohichne viddilennia	Vinnytsia		Ukraine	21018

Sponsors and Collaborators

• Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

• Statistical Analysis Plan - May 27, 2019
• Study Protocol - Aug 8, 2017

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT02996500
• Other Study ID Numbers: B7921005; 2016-002337-30; IRAK 4
• First Posted: Dec 19, 2016
• Last Update Posted: Feb 27, 2020
• Last Verified: Feb 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Arthritis; Arthritis, Rheumatoid; Tofacitinib

Study Results

Participant Flow

Arm/Group Title	Placebo	Tofa 10 mg	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Arm/Group Description	Participants received 4 matching PF-06650833 modified release (MR) placebo tablets once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.	Participants received 4 matching PF-06650833 MR placebo tablets QD and tofacitinib (Tofa) 10 mg (5 mg tablet BID) in 12 weeks treatment period.	Participants received 1 MR tablet of PF-06650833 20 mg and 3 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 3 MR tablets of PF-06650833 20 mg and 1 matching PF-06650833 MR placebo tablet QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 2 MR tablets of PF-06650833 100 mg and 2 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 4 MR tablets of PF-06650833 100 mg QD and 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.
Period Title: Overall Study
STARTED	39	43	39	50	50	48
COMPLETED	31	42	29	46	45	44
NOT COMPLETED	8	1	10	4	5	4

Baseline Characteristics

Arm/Group Title	Placebo	Tofa 10 mg	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg	Total
Arm/Group Description	Participants received 4 matching PF-06650833 modified release (MR) placebo tablets once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.	Participants received 4 matching PF-06650833 MR placebo tablets QD and tofacitinib (Tofa) 10 mg (5 mg tablet BID) in 12 weeks treatment period.	Participants received 1 MR tablet of PF-06650833 20 mg and 3 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 3 MR tablets of PF-06650833 20 mg and 1 matching PF-06650833 MR placebo tablet QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 2 MR tablets of PF-06650833 100 mg and 2 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 4 MR tablets of PF-06650833 100 mg QD and 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Total of all reporting groups
Overall Participants	39	43	39	50	50	48	269
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	54.9 (10.51)	52.7 (10.02)	55.9 (9.74)	51.0 (12.05)	53.6 (11.47)	54.8 (8.76)	53.7 (10.56)
Age, Customized (Count of Participants)
18-44 Years	7 17.9%	9 20.9%	5 12.8%	15 30%	11 22%	6 12.5%	53 19.7%
45-64 Years	26 66.7%	29 67.4%	27 69.2%	29 58%	32 64%	36 75%	179 66.5%
>=65 Years	6 15.4%	5 11.6%	7 17.9%	6 12%	7 14%	6 12.5%	37 13.8%
Sex: Female, Male (Count of Participants)
Female	30 76.9%	31 72.1%	31 79.5%	42 84%	39 78%	37 77.1%	210 78.1%
Male	9 23.1%	12 27.9%	8 20.5%	8 16%	11 22%	11 22.9%	59 21.9%
Race/Ethnicity, Customized (Count of Participants)
White	37 94.9%	43 100%	37 94.9%	47 94%	47 94%	43 89.6%	254 94.4%
Black or African American	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	2 5.1%	0 0%	1 2.6%	1 2%	2 4%	2 4.2%	8 3%
American Indian or Alaska Native	0 0%	0 0%	0 0%	1 2%	1 2%	0 0%	2 0.7%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Other	0 0%	0 0%	1 2.6%	1 2%	0 0%	3 6.3%	5 1.9%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in the Simplified Disease Activity Index (SDAI) at Week 12
Description	The SDAI is a continuous composite measure derived from components of the American College of Rheumatology (ACR) Core Dataset.The SDAI was calculated using the following formula: SDAI = Tender / Painful Joint Count(TJC) (using 28 joints) + Swollen Joint Count (SJC) (using 28 joints) + Patient Global Assessment of Arthritis (PtGA) (0-10 cm scale) + Physician's Global Assessment of Arthritis (PhGA) (0-10 cm scale) + high sensitivity C-reactive protein (hsCRP) (mg/dL). SDAI total score= 0-86. SDAI <=3.3 indicates disease remission, >3.4 to 11 = low disease activity, >11 to 26 = moderate disease activity, and >26 = high disease activity. The primary analysis utilized a Bayesian ANCOVA model with an informative placebo prior distribution with borrowing from tofacitinib historical placebo data. The confidence interval was credible interval in this statistical analysis. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized to the study, received at least 1 dose of the randomized investigational drug (PF-06650833, or placebo), and had data collected for this outcome measure at the time points assessed. It was pre-specified in the protocol to not summarize this efficacy endpoint for Tofa arm.

Arm/Group Title	Placebo	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Arm/Group Description	Participants received 4 matching PF-06650833 modified release (MR) placebo tablets once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.	Participants received 1 MR tablet of PF-06650833 20 mg and 3 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 3 MR tablets of PF-06650833 20 mg and 1 matching PF-06650833 MR placebo tablet QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 2 MR tablets of PF-06650833 100 mg and 2 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 4 modified release (MR) tablets of PF-06650833 400 mg once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.
Measure Participants	34	30	45	44	45
Mean (95% Confidence Interval) [units on a scale]	-13.87	-21.71	-22.83	-24.77	-25.16

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06650833 20 mg
	Comments	The confidence interval was credible interval in this analysis.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0050
	Comments
	Method	ANCOVA
	Comments	Bayesian analysis of covariance (ANCOVA) modeling framework was used with baseline SDAI score as a covariate.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-7.83
	Confidence Interval	(2-Sided) 95%; -13.73 to -1.97
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06650833 60 mg
	Comments	The confidence interval was credible interval in this analysis.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments	Bayesian analysis of covariance (ANCOVA) modeling framework was used with baseline SDAI score as a covariate.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-8.96
	Confidence Interval	(2-Sided) 95%; -14.37 to -3.66
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06650833 200 mg
	Comments	The confidence interval was credible interval in this analysis.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments	Bayesian analysis of covariance (ANCOVA) modeling framework was used with baseline SDAI score as a covariate.
Method of Estimation	Estimation Parameter	Median Difference (Net)
	Estimated Value	-10.89
	Confidence Interval	(2-Sided) 95%; -16.36 to -5.63
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06650833 400 mg
	Comments	The confidence interval was credible interval in this analysis.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments	Bayesian analysis of covariance (ANCOVA) modeling framework was used with baseline SDAI score as a covariate.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-11.29
	Confidence Interval	(2-Sided) 95%; -16.62 to -5.92
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline in SDAI at Weeks 4 and 8
Description	The SDAI is a continuous composite measure derived from components of the American College of Rheumatology (ACR) Core Dataset.The SDAI was calculated using the following formula: SDAI = TJC (using 28 joints) + SJC (using 28 joints) + PtGA (0-10 cm scale) + PhGA (0-10 cm scale) + hsCRP (mg/dL). SDAI total score= 0-86. SDAI <=3.3 indicates disease remission, >3.4 to 11 = low disease activity, >11 to 26 = moderate disease activity, and >26 = high disease activity. The descriptive summary of change from baseline in SDAI was based on a mixed effect model repeat measurement MMRM model with observed data. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.
Time Frame	Baseline, Weeks 4 and 8

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized to the study, received at least 1 dose of the randomized investigational drug (PF-06650833, or placebo), and had data collected for this outcome measure at the time points assessed. It was pre-specified in the protocol to not summarize this efficacy endpoint for Tofa arm.

Arm/Group Title	Placebo	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Arm/Group Description	Participants received 4 matching PF-06650833 modified release (MR) placebo tablets once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.	Participants received 1 MR tablet of PF-06650833 20 mg and 3 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 3 MR tablets of PF-06650833 20 mg and 1 matching PF-06650833 MR placebo tablet QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 2 MR tablets of PF-06650833 100 mg and 2 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 4 modified release (MR) tablets of PF-06650833 400 mg once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.
Measure Participants	39	39	50	50	48
Week 4	-10.78	-12.39	-14.29	-13.56	-12.30
Week 8	-17.07	-16.62	-18.85	-19.95	-21.15

3. Secondary Outcome

Title	Percentage of Participants With SDAI Low Disease Activity Score (LDAS) (SDAI <=11) at 4, 8, and 12 Weeks
Description	The SDAI is a continuous composite measure derived from components of the American College of Rheumatology (ACR) Core Dataset.The SDAI was calculated using the following formula: SDAI = TJC (using 28 joints) + SJC (using 28 joints) + PtGA (0-10 cm scale) + PhGA (0-10 cm scale) + hsCRP (mg/dL). The criterion of SDAI LDAS was SDAI<=11. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.
Time Frame	Weeks 4, 8 and 12

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized to the study, received at least 1 dose of the randomized investigational drug (PF-06650833, or placebo), and had data collected for this outcome measure at the time points assessed. It was pre-specified in the protocol to not summarize this efficacy endpoint for Tofa arm.

Arm/Group Title	Placebo	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Arm/Group Description	Participants received 4 matching PF-06650833 modified release (MR) placebo tablets once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.	Participants received 1 MR tablet of PF-06650833 20 mg and 3 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 3 MR tablets of PF-06650833 20 mg and 1 matching PF-06650833 MR placebo tablet QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 2 MR tablets of PF-06650833 100 mg and 2 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 4 modified release (MR) tablets of PF-06650833 400 mg once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.
Measure Participants	39	39	50	50	48
Week 4	8.1 20.8%	7.9 18.4%	12.2 31.3%	10.6 21.2%	8.5 17%
Week 8	14.7 37.7%	20.0 46.5%	17.4 44.6%	29.3 58.6%	33.3 66.6%
Week 12	26.5 67.9%	41.9 97.4%	28.9 74.1%	38.6 77.2%	42.2 84.4%

4. Secondary Outcome

Title	Percentage of Participants With SDAI Remission (SDAI <=3.3) at 4, 8, and 12 Weeks
Description	The SDAI is a continuous composite measure derived from components of the American College of Rheumatology (ACR) Core Dataset.The SDAI was calculated using the following formula: SDAI = TJC (using 28 joints) + SJC (using 28 joints) + PtGA (0-10 cm scale) + PhGA (0-10 cm scale) + hsCRP (mg/dL). The criterion of SDAI remission was SDAI<=3.3. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.
Time Frame	Weeks 4, 8 and 12

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized to the study, received at least 1 dose of the randomized investigational drug (PF-06650833, or placebo), and had data collected for this outcome measure at the time points assessed. It was pre-specified in the protocol to not summarize this efficacy endpoint for Tofa arm.

Arm/Group Title	Placebo	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Arm/Group Description	Participants received 4 matching PF-06650833 modified release (MR) placebo tablets once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.	Participants received 1 MR tablet of PF-06650833 20 mg and 3 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 3 MR tablets of PF-06650833 20 mg and 1 matching PF-06650833 MR placebo tablet QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 2 MR tablets of PF-06650833 100 mg and 2 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 4 modified release (MR) tablets of PF-06650833 400 mg once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.
Measure Participants	39	39	50	50	48
Week 4	0 0%	2.6 6%	2.0 5.1%	0 0%	2.1 4.2%
Week 8	0 0%	8.6 20%	0 0%	7.3 14.6%	2.2 4.4%
Week 12	2.9 7.4%	3.2 7.4%	2.2 5.6%	6.8 13.6%	8.9 17.8%

5. Secondary Outcome

Title	Percentage of Participants With Disease Activity Score-28 (4 Components Based on Erythrocyte Sedimentation Rate) (DAS28-4 [ESR]) LDAS (DAS28 <3.2) at 4, 8, and 12 Weeks
Description	The DAS assessment is a continuous composite measure derived using differential weighting given to each component. The components of the DAS28-4 (ESR) assessment included: tender joint count with 28 joints assessed, swollen joint count with 28 joints assessed, ESR and PGA. DAS28-4 (ESR) was calculated as 0.56 sqrt (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.70 ln(ESR [mm/first hour] + 0.014 (PtGA [mm]). Total score range: 0-9.4. Higher score indicated more disease activity. The criterion of DAS28-4 (ESR) LDAS was DAS28<3.2. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.
Time Frame	Weeks 4, 8 and 12

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized to the study, received at least 1 dose of the randomized investigational drug (PF-06650833, or placebo), and had data collected for this outcome measure at the time points assessed. It was pre-specified in the protocol to not summarize this efficacy endpoint for Tofa arm.

Arm/Group Title	Placebo	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Arm/Group Description	Participants received 4 matching PF-06650833 modified release (MR) placebo tablets once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.	Participants received 1 MR tablet of PF-06650833 20 mg and 3 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 3 MR tablets of PF-06650833 20 mg and 1 matching PF-06650833 MR placebo tablet QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 2 MR tablets of PF-06650833 100 mg and 2 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 4 modified release (MR) tablets of PF-06650833 400 mg once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.
Measure Participants	39	39	50	50	48
Week 4	2.9 7.4%	8.1 18.8%	6.4 16.4%	8.3 16.6%	4.3 8.6%
Week 8	8.6 22.1%	17.1 39.8%	13.6 34.9%	13.3 26.6%	12.8 25.6%
Week 12	17.6 45.1%	20.0 46.5%	24.4 62.6%	22.2 44.4%	17.8 35.6%

6. Secondary Outcome

Title	Percentage of Participants With DAS28-3 (ESR) LDAS (DAS28 <3.2) at 4, 8, and 12 Weeks
Description	The DAS assessment is a continuous composite measure derived using differential weighting given to each component. The components of the DAS28-3 (ESR) assessment included: tender joint count with 28 joints assessed, swollen joint count with 28 joints assessed and ESR. DAS28-3 (ESR) was calculated as 0.56 sqrt (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.70 ln(ESR [mm/first hour]*1.08+0.16. Total score range: 0-9.4. Higher score indicated more disease activity. The criterion of DAS28-3 LDAS was DAS28<3.2. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.
Time Frame	Weeks 4, 8 and 12

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized to the study, received at least 1 dose of the randomized investigational drug (PF-06650833, or placebo), and had data collected for this outcome measure at the time points assessed. It was pre-specified in the protocol to not summarize this efficacy endpoint for Tofa arm.

Arm/Group Title	Placebo	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Arm/Group Description	Participants received 4 matching PF-06650833 modified release (MR) placebo tablets once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.	Participants received 1 MR tablet of PF-06650833 20 mg and 3 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 3 MR tablets of PF-06650833 20 mg and 1 matching PF-06650833 MR placebo tablet QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 2 MR tablets of PF-06650833 100 mg and 2 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 4 modified release (MR) tablets of PF-06650833 400 mg once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.
Measure Participants	39	39	50	50	48
Week 4	5.7 14.6%	8.1 18.8%	10.6 27.2%	8.3 16.6%	4.3 8.6%
Week 8	8.6 22.1%	20.0 46.5%	15.9 40.8%	8.9 17.8%	14.9 29.8%
Week 12	20.6 52.8%	20.0 46.5%	22.2 56.9%	22.2 44.4%	15.6 31.2%

7. Secondary Outcome

Title	Percentage of Participants With Disease Activity Score-28 (4 Components Based on High-Sensitivity C-Reactive Protein) (DAS28-4 [CRP]) LDAS (DAS28 <3.2) at 4, 8, and 12 Weeks
Description	The DAS assessment is a continuous composite measure derived using differential weighting given to each component. The components of the DAS28-4 (CRP) assessment included: tender joint count with 28 joints assessed, swollen joint count with 28 joints assessed, hs-CRP and PtGA. DAS28-4 (CRP) was calculated as 0.56 sqrt (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.36 ln(CRP [mg/L] +1) + 0.014 (PtGA [mm]) + 0.96. Total score range: 0-9.4. Higher score indicated more disease activity. The criterion of DAS28-4 LDAS was DAS28<3.2. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.
Time Frame	Weeks 4, 8 and 12

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized to the study, received at least 1 dose of the randomized investigational drug (PF-06650833, or placebo), and had data collected for this outcome measure at the time points assessed. It was pre-specified in the protocol to not summarize this efficacy endpoint for Tofa arm.

Arm/Group Title	Placebo	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Arm/Group Description	Participants received 4 matching PF-06650833 modified release (MR) placebo tablets once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.	Participants received 1 MR tablet of PF-06650833 20 mg and 3 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 3 MR tablets of PF-06650833 20 mg and 1 matching PF-06650833 MR placebo tablet QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 2 MR tablets of PF-06650833 100 mg and 2 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 4 modified release (MR) tablets of PF-06650833 400 mg once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.
Measure Participants	39	39	50	50	48
Week 4	8.1 20.8%	13.2 30.7%	16.3 41.8%	12.8 25.6%	8.5 17%
Week 8	11.8 30.3%	20.0 46.5%	19.6 50.3%	26.8 53.6%	33.3 66.6%
Week 12	20.6 52.8%	38.7 90%	35.6 91.3%	40.9 81.8%	42.2 84.4%

8. Secondary Outcome

Title	Percentage of Participants With DAS28-3 (CRP) LDAS (DAS28 <3.2) at 4, 8, and 12 Weeks
Description	The DAS assessment is a continuous composite measure derived using differential weighting given to each component. The components of the DAS28-3 (CRP) assessment included: tender joint count with 28 joints assessed, swollen joint count with 28 joints assessed and hs-CRP. DAS28-3 (CRP) was calculated as 0.56 sqrt (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.36 ln(CRP [mg/L] +1)*1.10+ 1.15. Total score range: 0-9.4. Higher score indicated more disease activity. The criterion of DAS28-3 LDAS was DAS28<3.2. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.
Time Frame	Weeks 4, 8 and 12

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized to the study, received at least 1 dose of the randomized investigational drug (PF-06650833, or placebo), and had data collected for this outcome measure at the time points assessed. It was pre-specified in the protocol to not summarize this efficacy endpoint for Tofa arm.

Arm/Group Title	Placebo	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Arm/Group Description	Participants received 4 matching PF-06650833 modified release (MR) placebo tablets once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.	Participants received 1 MR tablet of PF-06650833 20 mg and 3 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 3 MR tablets of PF-06650833 20 mg and 1 matching PF-06650833 MR placebo tablet QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 2 MR tablets of PF-06650833 100 mg and 2 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 4 modified release (MR) tablets of PF-06650833 400 mg once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.
Measure Participants	39	39	50	50	48
Week 4	8.1 20.8%	10.5 24.4%	16.3 41.8%	17.0 34%	10.6 21.2%
Week 8	20.6 52.8%	22.9 53.3%	19.6 50.3%	34.1 68.2%	37.8 75.6%
Week 12	23.5 60.3%	41.9 97.4%	40.0 102.6%	47.7 95.4%	42.2 84.4%

9. Secondary Outcome

Title	Percentage of Participants With DAS28-4 (ESR) Remission (DAS28 <2.6) at 4, 8 and 12 Weeks
Description	The DAS assessment is a continuous composite measure derived using differential weighting given to each component. The components of the DAS28-4 (ESR) assessment included: tender joint count with 28 joints assessed, swollen joint count with 28 joints assessed, ESR and PtGA. DAS28-4 (ESR) was calculated as 0.56 sqrt (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.70 ln(ESR [mm/first hour] + 0.014 (PtGA [mm]). Total score range: 0-9.4. Higher score indicated more disease activity. The criterion of DAS28-4 remission was DAS28<2.6. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.
Time Frame	Weeks 4, 8 and 12

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized to the study, received at least 1 dose of the randomized investigational drug (PF-06650833, or placebo), and had data collected for this outcome measure at the time points assessed. It was pre-specified in the protocol to not summarize this efficacy endpoint for Tofa arm.

Arm/Group Title	Placebo	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Arm/Group Description	Participants received 4 matching PF-06650833 modified release (MR) placebo tablets once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.	Participants received 1 MR tablet of PF-06650833 20 mg and 3 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 3 MR tablets of PF-06650833 20 mg and 1 matching PF-06650833 MR placebo tablet QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 2 MR tablets of PF-06650833 100 mg and 2 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 4 modified release (MR) tablets of PF-06650833 400 mg once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.
Measure Participants	39	39	50	50	48
Week 4	0 0%	5.4 12.6%	2.1 5.4%	8.3 16.6%	2.1 4.2%
Week 8	5.7 14.6%	11.4 26.5%	9.1 23.3%	6.7 13.4%	10.6 21.2%
Week 12	5.9 15.1%	16.7 38.8%	13.3 34.1%	8.9 17.8%	11.1 22.2%

10. Secondary Outcome

Title	Percentage of Participants With DAS28-3 (ESR) Remission (DAS28 <2.6) at 4, 8 and 12 Weeks
Description	The DAS assessment is a continuous composite measure derived using differential weighting given to each component. The components of the DAS28-3 (ESR) assessment included: tender joint count with 28 joints assessed, swollen joint count with 28 joints assessed and ESR. DAS28-3 (ESR) was calculated as 0.56 sqrt (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.70 ln(ESR [mm/first hour]*1.08+0.16. Total score range: 0-9.4. Higher score indicated more disease activity. The criterion of DAS28-3 remission was DAS28<2.6. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.
Time Frame	Weeks 4, 8 and 12

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized to the study, received at least 1 dose of the randomized investigational drug (PF-06650833, or placebo), and had data collected for this outcome measure at the time points assessed. It was pre-specified in the protocol to not summarize this efficacy endpoint for Tofa arm.

Arm/Group Title	Placebo	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Arm/Group Description	Participants received 4 matching PF-06650833 modified release (MR) placebo tablets once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.	Participants received 1 MR tablet of PF-06650833 20 mg and 3 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 3 MR tablets of PF-06650833 20 mg and 1 matching PF-06650833 MR placebo tablet QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 2 MR tablets of PF-06650833 100 mg and 2 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 4 modified release (MR) tablets of PF-06650833 400 mg once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.
Measure Participants	39	39	50	50	48
Week 4	0 0%	2.7 6.3%	2.1 5.4%	6.3 12.6%	2.1 4.2%
Week 8	2.9 7.4%	8.6 20%	9.1 23.3%	6.7 13.4%	8.5 17%
Week 12	8.8 22.6%	10.0 23.3%	13.3 34.1%	11.1 22.2%	8.9 17.8%

11. Secondary Outcome

Title	Percentage of Participants With DAS28-4 (CRP) Remission (DAS28 <2.6) at 4, 8 and 12 Weeks
Description	The DAS assessment is a continuous composite measure derived using differential weighting given to each component. The components of the DAS28-4 (CRP) assessment included: tender joint count with 28 joints assessed, swollen joint count with 28 joints assessed, hs-CRP and PtGA. DAS28-4 (CRP) was calculated as 0.56 sqrt (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.36 ln(CRP [mg/L] +1) + 0.014 (PtGA [mm]) + 0.96. Total score range: 0-9.4. Higher score indicated more disease activity. The criterion of DAS28-4 remission was DAS28<2.6. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.
Time Frame	Weeks 4, 8 and 12

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized to the study, received at least 1 dose of the randomized investigational drug (PF-06650833, or placebo), and had data collected for this outcome measure at the time points assessed. It was pre-specified in the protocol to not summarize this efficacy endpoint for Tofa arm.

Arm/Group Title	Placebo	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Arm/Group Description	Participants received 4 matching PF-06650833 modified release (MR) placebo tablets once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.	Participants received 1 MR tablet of PF-06650833 20 mg and 3 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 3 MR tablets of PF-06650833 20 mg and 1 matching PF-06650833 MR placebo tablet QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 2 MR tablets of PF-06650833 100 mg and 2 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 4 modified release (MR) tablets of PF-06650833 400 mg once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.
Measure Participants	39	39	50	50	48
Week 4	2.7 6.9%	5.3 12.3%	8.2 21%	10.6 21.2%	6.4 12.8%
Week 8	8.8 22.6%	17.1 39.8%	10.9 27.9%	22.0 44%	13.3 26.6%
Week 12	14.7 37.7%	22.6 52.6%	17.8 45.6%	25.0 50%	24.4 48.8%

12. Secondary Outcome

Title	Percentage of Participants With DAS28-3 (CRP) Remission (DAS28 <2.6) at 4, 8 and 12 Weeks
Description	The DAS assessment is a continuous composite measure derived using differential weighting given to each component. The components of the DAS28-3 (CRP) assessment included: tender joint count with 28 joints assessed, swollen joint count with 28 joints assessed and hs-CRP. DAS28-3 (CRP) was calculated as 0.56 sqrt (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.36 ln(CRP [mg/L] +1)*1.10+1.15. Total score range: 0-9.4. Higher score indicated more disease activity. The criterion of DAS28-3 remission was DAS28<2.6. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.
Time Frame	Weeks 4, 8 and 12

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized to the study, received at least 1 dose of the randomized investigational drug (PF-06650833, or placebo), and had data collected for this outcome measure at the time points assessed. It was pre-specified in the protocol to not summarize this efficacy endpoint for Tofa arm.

Arm/Group Title	Placebo	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Arm/Group Description	Participants received 4 matching PF-06650833 modified release (MR) placebo tablets once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.	Participants received 1 MR tablet of PF-06650833 20 mg and 3 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 3 MR tablets of PF-06650833 20 mg and 1 matching PF-06650833 MR placebo tablet QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 2 MR tablets of PF-06650833 100 mg and 2 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 4 modified release (MR) tablets of PF-06650833 400 mg once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.
Measure Participants	39	39	50	50	48
Week 4	5.4 13.8%	5.3 12.3%	10.2 26.2%	8.5 17%	4.3 8.6%
Week 8	8.8 22.6%	14.3 33.3%	10.9 27.9%	22.0 44%	13.3 26.6%
Week 12	11.8 30.3%	25.8 60%	22.2 56.9%	22.7 45.4%	22.2 44.4%

13. Secondary Outcome

Title	Change From Baseline in DAS28-4 (ESR) at 4, 8 and 12 Weeks
Description	The DAS assessment is a continuous composite measure derived using differential weighting given to each component. The components of the DAS28-4 (ESR) assessment included: tender joint count with 28 joints assessed, swollen joint count with 28 joints assessed, ESR and PtGA. DAS28-4 (ESR) was calculated as 0.56 sqrt (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.70 ln(ESR [mm/first hour] + 0.014 (PtGA [mm]). Higher score indicated more disease activity. Total score range: 0-9.4. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.
Time Frame	Baseline, Weeks 4, 8 and 12

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized to the study, received at least 1 dose of the randomized investigational drug (PF-06650833, or placebo), and had data collected for this outcome measure at the time points assessed.It was pre-specified in the protocol to not summarize this efficacy endpoint for Tofa arm.

Arm/Group Title	Placebo	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Arm/Group Description	Participants received 4 matching PF-06650833 modified release (MR) placebo tablets once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.	Participants received 1 MR tablet of PF-06650833 20 mg and 3 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 3 MR tablets of PF-06650833 20 mg and 1 matching PF-06650833 MR placebo tablet QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 2 MR tablets of PF-06650833 100 mg and 2 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 4 modified release (MR) tablets of PF-06650833 400 mg once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.
Measure Participants	39	39	50	50	48
Week 4	-0.80	-1.15	-1.35	-1.14	-1.13
Week 8	-1.38	-1.59	-1.92	-1.77	-2.01
Week 12	-1.55	-1.85	-2.37	-2.23	-2.36

14. Secondary Outcome

Title	Change From Baseline in DAS28-3 (ESR) at 4, 8 and 12 Weeks
Description	The DAS assessment is a continuous composite measure derived using differential weighting given to each component. The components of the DAS28-3 (ESR) assessment included: tender joint count with 28 joints assessed, swollen joint count with 28 joints assessed and ESR. DAS28-3 (ESR) was calculated as 0.56 sqrt (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.70 ln(ESR) [mm/first hour]*1.08+0.16. Total score range: 0-9.4. Higher score indicated more disease activity. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.
Time Frame	Baseline, Weeks 4, 8 and 12

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized to the study, received at least 1 dose of the randomized investigational drug (PF-06650833, or placebo), and had data collected for this outcome measure at the time points assessed. It was pre-specified in the protocol to not summarize this efficacy endpoint for Tofa arm.

Arm/Group Title	Placebo	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Arm/Group Description	Participants received 4 matching PF-06650833 modified release (MR) placebo tablets once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.	Participants received 1 MR tablet of PF-06650833 20 mg and 3 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 3 MR tablets of PF-06650833 20 mg and 1 matching PF-06650833 MR placebo tablet QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 2 MR tablets of PF-06650833 100 mg and 2 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 4 modified release (MR) tablets of PF-06650833 400 mg once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.
Measure Participants	39	39	50	50	48
Week 4	-0.69	-1.08	-1.25	-1.08	-1.02
Week 8	-1.14	-1.52	-1.80	-1.62	-1.79
Week 12	-1.31	-1.69	-2.26	-2.05	-2.04

15. Secondary Outcome

Title	Change From Baseline in DAS28-4 (CRP) at 4, 8 and 12 Weeks
Description	The DAS assessment is a continuous composite measure derived using differential weighting given to each component. The components of the DAS28-4 (CRP) assessment included: tender joint count with 28 joints assessed, swollen joint count with 28 joints assessed, hs-CRP and PtGA. DAS28-4 (CRP) was calculated as 0.56 sqrt (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.36 ln(CRP [mg/L] +1) + 0.014 (PtGA [mm]) + 0.96. Total score range: 0-9.4. Higher score indicated more disease activity. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.
Time Frame	Baseline, Weeks 4, 8 and 12

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized to the study, received at least 1 dose of the randomized investigational drug (PF-06650833, or placebo), and had data collected for this outcome measure at the time points assessed. It was pre-specified in the protocol to not summarize this efficacy endpoint for Tofa arm.

Arm/Group Title	Placebo	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Arm/Group Description	Participants received 4 matching PF-06650833 modified release (MR) placebo tablets once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.	Participants received 1 MR tablet of PF-06650833 20 mg and 3 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 3 MR tablets of PF-06650833 20 mg and 1 matching PF-06650833 MR placebo tablet QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 2 MR tablets of PF-06650833 100 mg and 2 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 4 modified release (MR) tablets of PF-06650833 400 mg once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.
Measure Participants	39	39	50	50	48
Week 4	-0.72	-0.99	-1.21	-1.08	-0.99
Week 8	-1.20	-1.31	-1.59	-1.65	-1.73
Week 12	-1.38	-1.67	-1.94	-2.00	-2.12

16. Secondary Outcome

Title	Change From Baseline in DAS28-3 (CRP) at 4, 8 and 12 Weeks
Description	The DAS assessment is a continuous composite measure derived using differential weighting given to each component. The components of the DAS28-3 (CRP) assessment included: tender joint count with 28 joints assessed, swollen joint count with 28 joints assessed and hs-CRP. DAS28-3 (CRP) was calculated as 0.56 sqrt (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.36 ln(CRP [mg/L] +1)*1.10+ 1.15. Total score range: 0-9.4. Higher score indicated more disease activity. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.
Time Frame	Baseline, Weeks 4, 8 and 12

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized to the study, received at least 1 dose of the randomized investigational drug (PF-06650833, or placebo), and had data collected for this outcome measure at the time points assessed.It was pre-specified in the protocol to not summarize this efficacy endpoint for Tofa arm.

Arm/Group Title	Placebo	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Arm/Group Description	Participants received 4 matching PF-06650833 modified release (MR) placebo tablets once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.	Participants received 1 MR tablet of PF-06650833 20 mg and 3 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 3 MR tablets of PF-06650833 20 mg and 1 matching PF-06650833 MR placebo tablet QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 2 MR tablets of PF-06650833 100 mg and 2 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 4 modified release (MR) tablets of PF-06650833 400 mg once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.
Measure Participants	39	39	50	50	48
Week 4	-0.61	-0.93	-1.09	-1.01	-0.88
Week 8	-0.97	-1.24	-1.46	-1.52	-1.52
Week 12	-1.14	-1.53	-1.82	-1.83	-1.82

17. Secondary Outcome

Title	Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at 4, 8 and 12 Weeks
Description	ACR20 was calculated as a 20% improvement in TJC and SJC and 20% improvement in 3 of the 5 remaining ACR core set measures: PtGA and PhGA, pain, disability, and an acute phase reactant which for this study was CRP or ESR. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.
Time Frame	Weeks 4, 8 and 12

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized to the study, received at least 1 dose of the randomized investigational drug (PF-06650833, or placebo), and had data collected for this outcome measure at the time points assessed. It was pre-specified in the protocol to not summarize this efficacy endpoint for Tofa arm.

Arm/Group Title	Placebo	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Arm/Group Description	Participants received 4 matching PF-06650833 modified release (MR) placebo tablets once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.	Participants received 1 MR tablet of PF-06650833 20 mg and 3 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 3 MR tablets of PF-06650833 20 mg and 1 matching PF-06650833 MR placebo tablet QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 2 MR tablets of PF-06650833 100 mg and 2 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 4 modified release (MR) tablets of PF-06650833 400 mg once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.
Measure Participants	39	39	50	50	48
Week 4	30.8 79%	35.9 83.5%	42.0 107.7%	40.0 80%	37.5 75%
Week 8	46.2 118.5%	51.3 119.3%	58.0 148.7%	52.0 104%	64.6 129.2%
Week 12	51.3 131.5%	48.7 113.3%	66.0 169.2%	62.0 124%	70.8 141.6%

18. Secondary Outcome

Title	Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response at 4, 8 and 12 Weeks
Description	ACR50 was calculated as a 50% improvement in TJC and SJC and 50% improvement in 3 of the 5 remaining ACR core set measures: PtGA and PhGA, pain, disability, and an acute phase reactant which for this study was CRP or ESR. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.
Time Frame	Weeks 4, 8 and 12

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized to the study, received at least 1 dose of the randomized investigational drug (PF-06650833, or placebo), and had data collected for this outcome measure at the time points assessed. It was pre-specified in the protocol to not summarize this efficacy endpoint for Tofa arm.

Arm/Group Title	Placebo	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Arm/Group Description	Participants received 4 matching PF-06650833 modified release (MR) placebo tablets once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.	Participants received 1 MR tablet of PF-06650833 20 mg and 3 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 3 MR tablets of PF-06650833 20 mg and 1 matching PF-06650833 MR placebo tablet QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 2 MR tablets of PF-06650833 100 mg and 2 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 4 modified release (MR) tablets of PF-06650833 400 mg once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.
Measure Participants	39	39	50	50	48
Week 4	2.6 6.7%	10.3 24%	6.0 15.4%	6.0 12%	8.3 16.6%
Week 8	12.8 32.8%	23.1 53.7%	14.0 35.9%	22.0 44%	35.4 70.8%
Week 12	20.5 52.6%	25.6 59.5%	22.0 56.4%	40.0 80%	43.8 87.6%

19. Secondary Outcome

Title	Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response at 4, 8 and 12 Weeks
Description	ACR70 was calculated as a 70% improvement in TJC and SJC and 70% improvement in 3 of the 5 remaining ACR core set measures: PtGA and PhGA, pain, disability, and an acute phase reactant which for this study was CRP or ESR. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.
Time Frame	Weeks 4, 8 and 12

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized to the study, received at least 1 dose of the randomized investigational drug (PF-06650833, or placebo), and had data collected for this outcome measure at the time points assessed. It was pre-specified in the protocol to not summarize this efficacy endpoint for Tofa arm.

Arm/Group Title	Placebo	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Arm/Group Description	Participants received 4 matching PF-06650833 modified release (MR) placebo tablets once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.	Participants received 1 MR tablet of PF-06650833 20 mg and 3 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 3 MR tablets of PF-06650833 20 mg and 1 matching PF-06650833 MR placebo tablet QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 2 MR tablets of PF-06650833 100 mg and 2 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 4 modified release (MR) tablets of PF-06650833 400 mg once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.
Measure Participants	39	39	50	50	48
Week 4	0.0 0%	5.1 11.9%	0.0 0%	0.0 0%	4.2 8.4%
Week 8	2.6 6.7%	10.3 24%	0.0 0%	10.0 20%	6.3 12.6%
Week 12	5.1 13.1%	7.7 17.9%	6.0 15.4%	14.0 28%	10.4 20.8%

20. Secondary Outcome

Title	Change From Baseline in the Tender/Painful and Swollen Joint Counts at 4, 8 and 12 Weeks
Description	The TJC (28) included the following joints: shoulders, elbows, wrists, metatarsophalangeal (MCP) joints, PIP joints, and knees. This count was calculated from the TJC (68) assessed. The SJC (28) included the same joints as TJC (28), and was calculated from the SJC 66 assessed for swelling.Sixty eight (68) joints were assessed by a blinded joint assessor to determine the number of joints that were considered tender or painful. The 68 joints assessed were: temporomandibular, sternoclavicular, acromioclavicular; shoulder, elbow, wrist, MCPs, thumb interphalangeal, proximal interphalangeals, and distal interphalangeals; hip, knee, ankle, tarsus, metatarsophalangeals, great toe interphalangeal, proximal and distal interphalangeals combined. Sixty-six (66) joints were assessed for swelling, the same as those listed for TJC, excluding the right and left hip joints. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.
Time Frame	Baseline, Weeks 4, 8 and 12

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized to the study, received at least 1 dose of the randomized investigational drug (PF-06650833, or placebo), and had data collected for this outcome measure at the time points assessed. It was pre-specified in the protocol to not summarize this efficacy endpoint for Tofa arm.

Arm/Group Title	Placebo	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Arm/Group Description	Participants received 4 matching PF-06650833 modified release (MR) placebo tablets once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.	Participants received 1 MR tablet of PF-06650833 20 mg and 3 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 3 MR tablets of PF-06650833 20 mg and 1 matching PF-06650833 MR placebo tablet QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 2 MR tablets of PF-06650833 100 mg and 2 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 4 modified release (MR) tablets of PF-06650833 400 mg once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.
Measure Participants	39	39	50	50	48
SJC (28) at Week 4	-4.4 (6.01)	-4.8 (3.64)	-4.4 (3.76)	-5.0 (4.87)	-3.8 (4.25)
SJC (28) at Week 8	-6.1 (6.75)	-6.0 (4.70)	-6.1 (4.80)	-7.0 (5.31)	-6.8 (5.75)
SJC (28) at Week 12	-6.3 (5.61)	-6.8 (5.21)	-6.6 (5.38)	-8.1 (5.73)	-8.2 (6.01)
TJC (28) at Week 4	-4.0 (5.99)	-4.9 (5.01)	-5.5 (5.12)	-4.8 (6.14)	-4.4 (5.36)
TJC (28) at Week 8	-5.9 (7.16)	-6.9 (6.18)	-7.0 (5.83)	-7.5 (7.13)	-7.8 (6.72)
TJC (28) at Week 12	-7.5 (6.39)	-8.6 (6.36)	-9.5 (6.14)	-9.9 (7.24)	-9.6 (6.65)
SJC (66) at Week 4	-6.2 (10.82)	-6.5 (5.07)	-6.3 (5.27)	-8.6 (9.00)	-6.2 (8.00)
SJC (66) at Week 8	-9.0 (10.87)	-8.2 (7.03)	-8.5 (6.74)	-11.0 (8.81)	-10.0 (9.92)
SJC (66) at Week 12	-9.4 (9.92)	-9.6 (7.76)	-8.8 (7.11)	-12.5 (9.00)	-11.6 (10.19)
TJC (68) at Week 4	-4.9 (11.28)	-8.7 (8.96)	-9.1 (8.45)	-9.1 (12.22)	-7.8 (9.60)
TJC (68) at Week 8	-10.0 (13.41)	-10.9 (10.48)	-11.3 (9.46)	-14.0 (14.61)	-12.2 (11.40)
TJC (68) at Week 12	-11.5 (12.24)	-13.5 (11.44)	-15.5 (11.30)	-18.1 (15.00)	-14.8 (11.98)

21. Secondary Outcome

Title	Change From Baseline in High-Sensitivity C-Reactive Protein (Hs-CRP) at 4, 8 and 12 Weeks
Description	Serum samples were analyzed to determine the level of hs-CRP, which was an acute-phase reactant. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.
Time Frame	Baseline, Weeks 4, 8 and 12

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized to the study, received at least 1 dose of the randomized investigational drug (PF-06650833, or placebo), and had data collected for this outcome measure at the time points assessed. It was pre-specified in the protocol to not summarize this efficacy endpoint for Tofa arm.

Arm/Group Title	Placebo	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Arm/Group Description	Participants received 4 matching PF-06650833 modified release (MR) placebo tablets once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.	Participants received 1 MR tablet of PF-06650833 20 mg and 3 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 3 MR tablets of PF-06650833 20 mg and 1 matching PF-06650833 MR placebo tablet QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 2 MR tablets of PF-06650833 100 mg and 2 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 4 modified release (MR) tablets of PF-06650833 400 mg once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.
Measure Participants	39	39	50	50	48
Week 4	0.22	-0.15	-0.66	-0.66	-0.65
Week 8	0.12	0.07	-0.91	-0.62	-0.61
Week 12	-0.07	-0.23	-0.74	-0.68	-0.64

22. Secondary Outcome

Title	Change From Baseline in the Physician's Global Assessment of Arthritis (PhGA) at 4, 8, and 12 Weeks
Description	The investigator assessed how the participant's overall arthritis appeared at the time of the visit. This was an evaluation based on the participant's disease symptoms, functional capacity and physical examination, and was independent of the participant's reported assessments of PtGA (patient's global assessment of arthritis). The investigator's response was recorded using a 100 mm visual analog scale (VAS), with the 0 mm end labeled "None" and the 100 mm end labeled "Extreme". Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.
Time Frame	Baseline, Weeks 4, 8 and 12

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized to the study, received at least 1 dose of the randomized investigational drug (PF-06650833, or placebo), and had data collected for this outcome measure at the time points assessed.It was pre-specified in the protocol to not summarize this efficacy endpoint for Tofa arm.

Arm/Group Title	Placebo	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Arm/Group Description	Participants received 4 matching PF-06650833 modified release (MR) placebo tablets once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.	Participants received 1 MR tablet of PF-06650833 20 mg and 3 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 3 MR tablets of PF-06650833 20 mg and 1 matching PF-06650833 MR placebo tablet QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 2 MR tablets of PF-06650833 100 mg and 2 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 4 modified release (MR) tablets of PF-06650833 400 mg once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.
Measure Participants	39	39	50	50	48
Week 4	-14.30	-18.54	-22.51	-18.34	-18.06
Week 8	-25.86	-26.80	-27.76	-27.86	-29.97
Week 12	-28.16	-30.28	-33.05	-34.27	-36.34

23. Secondary Outcome

Title	Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Treatment-Related TEAEs
Description	AE was defined as any untoward medical occurrence in a clinical investigation participant administered a product or medical device, regardless of the causal relationship to study treatment. Treatment-emergent AEs (TEAEs) were defined as AEs which occurred for the first time during the effective duration of treatment or AEs that increased in severity during treatment. Serious AEs (SAEs) were defined as any untoward medical occurrence at any dose that resulted in death; was life-threatening (immediate risk of death); required inpatient hospitalization or caused prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduction normal life functions). AEs included SAEs and non-serious AEs. Causality to study treatment was determined by the investigator.
Time Frame	Baseline up to 28 calendar days after the last administration of the investigational product (about 21 months)

Outcome Measure Data

Analysis Population Description

The safety analysis population included the participants who received at least 1 dose of the investigational drug.

Arm/Group Title	Placebo	Tofa 10 mg	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Arm/Group Description	Participants received 4 matching PF-06650833 modified release (MR) placebo tablets once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.	Participants received 4 matching PF-06650833 MR placebo tablets QD and tofacitinib (Tofa) 10 mg (5 mg tablet BID) in 12 weeks treatment period.	Participants received 1 MR tablet of PF-06650833 20 mg and 3 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 3 MR tablets of PF-06650833 20 mg and 1 matching PF-06650833 MR placebo tablet QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 2 MR tablets of PF-06650833 100 mg and 2 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 4 modified release (MR) tablets of PF-06650833 400 mg once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.
Measure Participants	39	43	39	50	50	48
TEAEs (all causality)	17 43.6%	17 39.5%	20 51.3%	27 54%	19 38%	23 47.9%
TEAEs (treatment-related)	8 20.5%	6 14%	12 30.8%	8 16%	8 16%	6 12.5%
SAEs (all causality)	1 2.6%	1 2.3%	1 2.6%	1 2%	1 2%	3 6.3%
SAEs (treatment-related)	0 0%	0 0%	1 2.6%	0 0%	0 0%	0 0%

24. Secondary Outcome

Title	Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)
Description	Laboratory evaluation included hematology, clinical chemistry, and urinalysis. Laboratory parameters included: hematology (hemoglobin, hematocrit, red blood cell, platelet and white blood cell count, neutrophils, eosinophils, monocytes, basophils and lymphocytes), chemistry (blood urea nitrogen, creatinine, sodium, potassium, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, albumin, total protein and serum pregnancy test [for all female participants]) and urine (urine pregnancy test [for all female participants]). Each parameter was evaluated against commonly used and widely accepted criteria. Clinical significance of laboratory parameters was determined at the investigator's discretion. The investigator judged the abnormality.
Time Frame	Baseline up to 28 calendar days after the last administration of the investigational product (about 21 months)

Outcome Measure Data

Analysis Population Description

The safety analysis population included all participants who received at least 1 dose of investigational drug and were evaluable for laboratory abnormalities.

Arm/Group Title	Placebo	Tofa 10 mg	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Arm/Group Description	Participants received 4 matching PF-06650833 modified release (MR) placebo tablets once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.	Participants received 4 matching PF-06650833 MR placebo tablets QD and tofacitinib (Tofa) 10 mg (5 mg tablet BID) in 12 weeks treatment period.	Participants received 1 MR tablet of PF-06650833 20 mg and 3 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 3 MR tablets of PF-06650833 20 mg and 1 matching PF-06650833 MR placebo tablet QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 2 MR tablets of PF-06650833 100 mg and 2 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 4 modified release (MR) tablets of PF-06650833 400 mg once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.
Measure Participants	38	43	39	50	49	48
Count of Participants [Participants]	30 76.9%	32 74.4%	30 76.9%	36 72%	41 82%	38 79.2%

25. Secondary Outcome

Title	Number of Participants With Vital Signs Data Meeting Pre-sepcified Criteria
Description	Vital Signs tests included sitting systolic blood pressure (SBP) and diastolic blood pressure (DBP) and pulse rate. Vital signs categorical summarization criteria were 1), systolic BP (SBP) <90 millimeters of mercury (mm Hg) or change from baseline (Chg) >=30mm Hg; diastolic BP (DBP) <50mm Hg or change from baseline >=20mm Hg; 2), pulse rate <40bpm or > 120bpm.
Time Frame	Baseline up to 28 calendar days after the last administration of the investigational product (about 21 months)

Outcome Measure Data

Analysis Population Description

The safety analysis population included all participants who received at least 1 dose of investigational drug and had evaluable vital signs data.

Arm/Group Title	Placebo	Tofa 10 mg	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Arm/Group Description	Participants received 4 matching PF-06650833 modified release (MR) placebo tablets once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.	Participants received 4 matching PF-06650833 MR placebo tablets QD and tofacitinib (Tofa) 10 mg (5 mg tablet BID) in 12 weeks treatment period.	Participants received 1 MR tablet of PF-06650833 20 mg and 3 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 3 MR tablets of PF-06650833 20 mg and 1 matching PF-06650833 MR placebo tablet QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 2 MR tablets of PF-06650833 100 mg and 2 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 4 modified release (MR) tablets of PF-06650833 400 mg once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.
Measure Participants	38	43	39	50	49	48
Sitting Diastolic BP < 50 mm Hg	1 2.6%	0 0%	0 0%	0 0%	0 0%	0 0%
Sitting Pulse Rate < 40 bpm	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Sitting Pulse Rate > 120 bpm	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Sitting Systolic BP < 90 mm Hg	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Increase: Sitting Systolic BP Chg>= 30 mm Hg	0 0%	0 0%	1 2.6%	1 2%	0 0%	1 2.1%
Increase: Sitting Diastolic BP Chg >= 20 mmHg	1 2.6%	2 4.7%	3 7.7%	0 0%	1 2%	2 4.2%
Decrease: Sitting Systolic BP Chg >= 30 mm Hg	2 5.1%	3 7%	0 0%	2 4%	3 6%	3 6.3%
Decrease: Sitting Diastolic BP Chg >= 20 mm Hg	2 5.1%	4 9.3%	2 5.1%	4 8%	3 6%	2 4.2%

26. Secondary Outcome

Title	Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-sepcified Criteria
Description	ECG evaluation included: PR interval, time from ECG Q wave to the end of the S wave corresponding to ventricle depolarization (QRS interval), time between the start of the Q wave and the end of the T wave in the heart's electrical cycle (QT interval), QT interval corrected for heart rate using Fridericia's formula (QTcF interval), and QTc calculated using Bazett's correction factor (QTcB interval).
Time Frame	Baseline up to 28 calendar days after the last administration of the investigational product (about 21 months)

Outcome Measure Data

Analysis Population Description

The safety analysis population included all participants who received at least 1 dose of investigational drug and had evaluable ECG data.

Arm/Group Title	Placebo	Tofa 10 mg	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Arm/Group Description	Participants received 4 matching PF-06650833 modified release (MR) placebo tablets once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.	Participants received 4 matching PF-06650833 MR placebo tablets QD and tofacitinib (Tofa) 10 mg (5 mg tablet BID) in 12 weeks treatment period.	Participants received 1 MR tablet of PF-06650833 20 mg and 3 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 3 MR tablets of PF-06650833 20 mg and 1 matching PF-06650833 MR placebo tablet QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 2 MR tablets of PF-06650833 100 mg and 2 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 4 modified release (MR) tablets of PF-06650833 400 mg once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.
Measure Participants	38	43	39	50	49	48
PR interval >=300 msec	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
QRS duration >=140 msec	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
QT interval >=500 msec	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
QTcB interval >=450 and <480 msec	5 12.8%	4 9.3%	5 12.8%	4 8%	5 10%	13 27.1%
QTcB interval >=480 and <500 msec	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
QTcB interval >=500 msec	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
QTcF interval >=450 and <480 msec	0 0%	1 2.3%	1 2.6%	0 0%	1 2%	4 8.3%
QTcF interval >=480 and <500 msec	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
QTcF interval >=500 msec	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
PR interval increase>=25/50%	0 0%	0 0%	0 0%	0 0%	1 2%	0 0%
QRS duration increase>=50%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
QTcB interval increase>=30 and increase <60 msec	3 7.7%	6 14%	9 23.1%	3 6%	4 8%	7 14.6%
QTcB interval increase>=60 msec	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
QTcF interval increase>=30 and increase <60 msec	2 5.1%	4 9.3%	5 12.8%	0 0%	5 10%	5 10.4%
QTcF interval increase>=60 msec	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

27. Secondary Outcome

Title	Number of Participants With Urinalysis Data Meeting Pre-specified Criteria
Description	The urine sample was collected for central laboratory urinalysis and urine microscopy. The urinalysis included pH, protein, glucose, erythrocytes, leukocytes, ketones, nitrite, urobilinogen, urine bilirubin, urine hemoglobin, leukocyte esterase, granular casts, hyaline casts, bacteria, atypical, needle-like crystals urine, specific gravity, microscopy and urine albumin test.
Time Frame	Baseline up to 28 calendar days after the last administration of the investigational product (about 21 months)

Outcome Measure Data

Analysis Population Description

The safety analysis population included all participants who received at least 1 dose of investigational drug and had evaluable urinalysis data

Arm/Group Title	Placebo	Tofa 10 mg	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Arm/Group Description	Participants received 4 matching PF-06650833 modified release (MR) placebo tablets once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.	Participants received 4 matching PF-06650833 MR placebo tablets QD and tofacitinib (Tofa) 10 mg (5 mg tablet BID) in 12 weeks treatment period.	Participants received 1 MR tablet of PF-06650833 20 mg and 3 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 3 MR tablets of PF-06650833 20 mg and 1 matching PF-06650833 MR placebo tablet QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 2 MR tablets of PF-06650833 100 mg and 2 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 4 modified release (MR) tablets of PF-06650833 400 mg once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.
Measure Participants	38	43	39	50	49	48
Specific gravity <1.003	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Specific gravity >1.030	3 7.7%	0 0%	0 0%	3 6%	2 4%	2 4.2%
pH <4.5	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
pH >8	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Urine glucose >=1	0 0%	0 0%	4 10.3%	2 4%	2 4%	2 4.2%
Ketones >=1	3 7.7%	0 0%	1 2.6%	2 4%	1 2%	1 2.1%
Urine protein >=1	0 0%	0 0%	0 0%	0 0%	1 2%	0 0%
Urine hemoglobin >=1	7 17.9%	5 11.6%	6 15.4%	5 10%	12 24%	6 12.5%
Urobilinogen >=1	1 2.6%	0 0%	0 0%	0 0%	0 0%	1 2.1%
Urine bilirubin >=1	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Nitrite >=1	3 7.7%	5 11.6%	3 7.7%	1 2%	9 18%	11 22.9%
Leukocyte esterase >=1	16 41%	15 34.9%	14 35.9%	14 28%	19 38%	19 39.6%
Urine erythrocytes(/HPF) >=20	1 2.6%	2 4.7%	3 7.7%	1 2%	3 6%	3 6.3%
Urine leukocytes (/HPF) >=20	4 10.3%	3 7%	2 5.1%	2 4%	7 14%	7 14.6%
Granular casts (/LPF) >1	1 2.6%	1 2.3%	0 0%	0 0%	0 0%	0 0%
Hyaline Casts (/LPF)	4 10.3%	4 9.3%	6 15.4%	7 14%	4 8%	3 6.3%
Bacteria >20	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Atypical, needle-like crystals urine >=1	0 0%	0 0%	0 0%	0 0%	2 4%	0 0%

28. Secondary Outcome

Title	Change From Baseline in the Patient's Assessment of Arthritis Pain (PAAP) Visual Analogue Scale (VAS) at Weeks 4, 8, 12
Description	Patients assess the severity of their arthritis pain using a 100 mm VAS by placing a mark on the scale between 0 (no pain) and 100 (most severe pain), which corresponds to the magnitude of their pain. This assessment was performed early in the clinic visit and before the participant had extensive contact with site personnel and/or Investigator. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.
Time Frame	Baseline, Weeks 4, 8 and 12

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized to the study, received at least 1 dose of the randomized investigational drug (PF-06650833, or placebo), and had data collected for this outcome measure at the time points assessed. It was pre-specified in the protocol to not summarize this efficacy endpoint for Tofa arm.

Arm/Group Title	Placebo	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Arm/Group Description	Participants received 4 matching PF-06650833 modified release (MR) placebo tablets once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.	Participants received 1 MR tablet of PF-06650833 20 mg and 3 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 3 MR tablets of PF-06650833 20 mg and 1 matching PF-06650833 MR placebo tablet QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 2 MR tablets of PF-06650833 100 mg and 2 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 4 modified release (MR) tablets of PF-06650833 400 mg once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.
Measure Participants	39	39	50	50	48
Week 4	-12.8 (18.85)	-11.5 (19.44)	-16.8 (20.19)	-9.5 (16.10)	-11.3 (21.22)
Week 8	-22.4 (20.05)	-15.4 (21.32)	-22.2 (18.88)	-20.5 (23.70)	-23.5 (20.42)
Week 12	-25.9 (26.39)	-21.4 (25.03)	-23.0 (21.46)	-25.7 (24.02)	-31.08 (23.70)

29. Secondary Outcome

Title	Change From Baseline in the Patient Global Assessment of Arthritis (PtGA) VAS at Weeks 4, 8, 12
Description	Patients answer the following question: "Considering all the ways your arthritis affects you, how are you feeling today?" The patient's response is recorded using a 100 mm VAS. This assessment was performed early in the clinic visit and before the participant had extensive contact with site personnel and/or Investigator. The higher score indicated more severe disease. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.
Time Frame	Baseline, Weeks 4, 8 and 12

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized to the study, received at least 1 dose of the randomized investigational drug (PF-06650833, or placebo), and had data collected for this outcome measure at the time points assessed. It was pre-specified in the protocol to not summarize this efficacy endpoint for Tofa arm.

Arm/Group Title	Placebo	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Arm/Group Description	Participants received 4 matching PF-06650833 modified release (MR) placebo tablets once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.	Participants received 1 MR tablet of PF-06650833 20 mg and 3 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 3 MR tablets of PF-06650833 20 mg and 1 matching PF-06650833 MR placebo tablet QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 2 MR tablets of PF-06650833 100 mg and 2 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 4 modified release (MR) tablets of PF-06650833 400 mg once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.
Measure Participants	39	39	50	50	48
Week 4	-12.0 (21.55)	-10.0 (16.68)	-14.9 (20.52)	-10.7 (19.11)	-13.7 (20.29)
Week 8	-24.9 (21.25)	-13.1 (23.47)	-19.6 (19.60)	-22.2 (27.34)	-25.3 (20.74)
Week 12	-25.9 (25.03)	-20.0 (23.12)	-19.7 (25.71)	-26.5 (25.23)	-34.2 (22.81)

30. Secondary Outcome

Title	Change From Baseline in the Health Assessment Questionnaire - Disability Index (HAQ-DI) at Weeks 4, 8, and 12
Description	The HAQ-DI was defined as participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.
Time Frame	Baseline, Weeks 4, 8 and 12

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized to the study and received at least 1 dose of the randomized investigational drug (PF-06650833, tofacitinib, or placebo).

Arm/Group Title	Placebo	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Arm/Group Description	Participants received 4 matching PF-06650833 modified release (MR) placebo tablets once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.	Participants received 1 MR tablet of PF-06650833 20 mg and 3 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 3 MR tablets of PF-06650833 20 mg and 1 matching PF-06650833 MR placebo tablet QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 2 MR tablets of PF-06650833 100 mg and 2 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 4 modified release (MR) tablets of PF-06650833 400 mg once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.
Measure Participants	39	39	50	50	48
Week 4	-0.2 (0.46)	-0.2 (0.44)	-0.3 (0.40)	-0.2 (0.43)	-0.3 (0.49)
Week 8	-0.4 (0.47)	-0.4 (0.54)	-0.4 (0.41)	-0.4 (0.56)	-0.5 (0.59)
Week 12	-0.5 (0.47)	-0.5 (0.60)	-0.5 (0.48)	-0.5 (0.66)	-0.6 (0.59)

31. Secondary Outcome

Title	Change From Baseline in the 36 Item Short Form Health Survey (SF-36) Version 2 (Acute) 8 Domain Scores at Week 12
Description	The SF-36 version 2 (acute) is a 36 item generic health status measure. It measures 8 general health domains: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional and mental health. The SF-36 summary scores range from 0-100, with higher scores representing better self-reported health. This was performed early in the clinic visit and before the participant had extensive contact with site personnel and/or Investigator. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized to the study, received at least 1 dose of the randomized investigational drug (PF-06650833, or placebo), and had data collected for this outcome measure at the time points assessed. It was pre-specified in the protocol to not summarize this efficacy endpoint for Tofa arm.

Arm/Group Title	Placebo	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Arm/Group Description	Participants received 4 matching PF-06650833 modified release (MR) placebo tablets once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.	Participants received 1 MR tablet of PF-06650833 20 mg and 3 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 3 MR tablets of PF-06650833 20 mg and 1 matching PF-06650833 MR placebo tablet QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 2 MR tablets of PF-06650833 100 mg and 2 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 4 modified release (MR) tablets of PF-06650833 400 mg once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.
Measure Participants	39	39	50	50	48
Physical functioning domain	3.311 (11.5441)	4.885 (8.4161)	6.318 (8.6700)	5.412 (9.7871)	7.322 (11.2219)
Role-physical domain	6.316 (9.7393)	5.773 (10.0629)	6.173 (8.5158)	6.151 (9.8448)	6.734 (9.3707)
Bodily pain domain	7.840 (7.2950)	6.543 (9.3835)	7.280 (8.1633)	7.071 (9.6901)	10.422 (8.6959)
General health domain	5.775 (6.7414)	5.531 (6.4448)	4.856 (6.5230)	4.916 (8.4424)	7.046 (8.7992)
Vitality domain	8.717 (8.0179)	7.049 (9.9149)	7.354 (9.9326)	6.453 (10.2902)	8.182 (8.7136)
Social function domain	5.061 (11.6125)	6.418 (11.6517)	6.430 (12.2952)	6.095 (12.1659)	8.485 (9.2070)
Role-emotional domain	7.683 (11.2028)	4.396 (11.1492)	5.103 (12.5489)	6.730 (12.7335)	6.646 (11.4190)
Mental health domain	7.497 (11.8826)	5.161 (11.7376)	5.661 (13.7839)	7.080 (12.9887)	8.866 (10.4266)

32. Secondary Outcome

Title	Change From Baseline in the Physical Component Score (PCS) and Mental Component Score (MCS) at Week 12
Description	The SF 36 version 2 (acute) is a 36 item generic health status measure. It measures 8 general health domains. These domains can also be summarized as physical component score (PCS) and mental component score (MCS). The PCS and MCS summary scores range from 0-100, with higher scores representing better self-reported health. The lower the score the more disability. This was performed early in the clinic visit and before the participant had extensive contact with site personnel and/or Investigator. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized to the study, received at least 1 dose of the randomized investigational drug (PF-06650833, or placebo), and had data collected for this outcome measure at the time points assessed. It was pre-specified in the protocol to not summarize this efficacy endpoint for Tofa arm.

Arm/Group Title	Placebo	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Arm/Group Description	Participants received 4 matching PF-06650833 modified release (MR) placebo tablets once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.	Participants received 1 MR tablet of PF-06650833 20 mg and 3 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 3 MR tablets of PF-06650833 20 mg and 1 matching PF-06650833 MR placebo tablet QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 2 MR tablets of PF-06650833 100 mg and 2 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 4 modified release (MR) tablets of PF-06650833 400 mg once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.
Measure Participants	39	39	50	50	48
PCS	4.635 (7.8031)	5.728 (7.4254)	6.304 (7.6091)	5.212 (8.0162)	7.476 (8.3473)
MCS	7.995 (11.5950)	5.241 (10.4860)	5.425 (13.6873)	6.749 (12.0657)	7.759 (9.4263)

33. Secondary Outcome

Title	Change From Baseline in the European Quality of Life 5 Dimensions-3 Level (EQ-5D-3L) Score at Week 12
Description	The EQ-5D-3L health state profile is a patient completed questionnaire designed to assess impact on health related quality of life in 5 domains: mobility, self care, usual activities, pain/discomfort, and anxiety/depression. Additionally, scores from the 5 domains might have been used to calculate a single index value, also known as a utility score. The validity and reliability of the EQ-5D-3L have been established in a number of disease states, including RA. EQ-5D-3L scores marked health status from 0 and 100. There were notes at the both ends of the scale that the bottom rate (0) corresponded to " the worst health you could imagine", and the highest rate (100) corresponded to "the best health you could imagine". Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized to the study, received at least 1 dose of the randomized investigational drug (PF-06650833, or placebo), and had data collected for this outcome measure at the time points assessed. It was pre-specified in the protocol to not summarize this efficacy endpoint for Tofa arm.

Arm/Group Title	Placebo	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Arm/Group Description	Participants received 4 matching PF-06650833 modified release (MR) placebo tablets once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.	Participants received 1 MR tablet of PF-06650833 20 mg and 3 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 3 MR tablets of PF-06650833 20 mg and 1 matching PF-06650833 MR placebo tablet QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 2 MR tablets of PF-06650833 100 mg and 2 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 4 modified release (MR) tablets of PF-06650833 400 mg once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.
Measure Participants	39	39	50	50	48
EQ visual analogue scale (VAS) score	13.265 (18.8540)	11.129 (24.6181)	11.913 (20.3795)	20.909 (24.5895)	20.778 (20.6792)
Index value	0.132 (0.2030)	0.056 (0.1957)	0.118 (0.1661)	0.143 (0.2445)	0.190 (0.2201)

34. Secondary Outcome

Title	Change From Baseline in the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Total Score at Week 12
Description	The FACIT-F is a patient completed questionnaire consisting of 13 items that assess fatigue. Instrument scoring yields a range from 0 to 52, with higher scores representing better patient status (less fatigue). This questionnaire was performed early in the clinic visit and before the participant had extensive contact with site personnel and/or investigator. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized to the study and received at least 1 dose of the randomized investigational drug (PF-06650833, tofacitinib, or placebo). It was pre-specified in the protocol to not summarize this efficacy endpoint for Tofa arm.

Arm/Group Title	Placebo	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Arm/Group Description	Participants received 4 matching PF-06650833 modified release (MR) placebo tablets once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.	Participants received 1 MR tablet of PF-06650833 20 mg and 3 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 3 MR tablets of PF-06650833 20 mg and 1 matching PF-06650833 MR placebo tablet QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 2 MR tablets of PF-06650833 100 mg and 2 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.	Participants received 4 modified release (MR) tablets of PF-06650833 400 mg once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.
Measure Participants	34	31	46	45	45
Mean (Standard Deviation) [units on a scale]	8.4 (8.76)	4.6 (10.92)	6.8 (8.33)	7.2 (11.45)	9.5 (9.68)

Adverse Events

Time Frame	Baseline up to 28 calendar days after the last administration of the investigational product (about 21 months)
Adverse Event Reporting Description	The same event may appear as both an AE and a SAE. An event may be categorized as serious in 1 participant and as non-serious in another participant, or 1 participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Arm/Group Title	Placebo		Tofa 10 mg		PF-06650833 20 mg		PF-06650833 60 mg		PF-06650833 200 mg		PF-06650833 400 mg
Arm/Group Description	Participants received 4 matching PF-06650833 modified release (MR) placebo tablets once daily (QD) and 1 matching tofacitinib placebo tablet twice a day (BID) in 12 weeks treatment period.		Participants received 4 matching PF-06650833 MR placebo tablets QD and tofacitinib (Tofa) 10 mg (5 mg tablet BID) in 12 weeks treatment period.		Participants received 1 MR tablet of PF-06650833 20 mg and 3 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.		Participants received 3 MR tablets of PF-06650833 20 mg and 1 matching PF-06650833 MR placebo tablet QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.		Participants received 2 MR tablets of PF-06650833 100 mg and 2 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.		Participants received 4 MR tablets of PF-06650833 100 mg QD and 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.
All Cause Mortality
	Placebo		Tofa 10 mg		PF-06650833 20 mg		PF-06650833 60 mg		PF-06650833 200 mg		PF-06650833 400 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/39 (0%)		0/43 (0%)		0/39 (0%)		0/50 (0%)		0/50 (0%)		0/48 (0%)
Serious Adverse Events
	Placebo		Tofa 10 mg		PF-06650833 20 mg		PF-06650833 60 mg		PF-06650833 200 mg		PF-06650833 400 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/39 (2.6%)		1/43 (2.3%)		1/39 (2.6%)		1/50 (2%)		1/50 (2%)		3/48 (6.3%)
Cardiac disorders
Acute myocardial infarction	0/39 (0%)		0/43 (0%)		0/39 (0%)		0/50 (0%)		0/50 (0%)		1/48 (2.1%)
Hepatobiliary disorders
Hepatotoxicity	0/39 (0%)		0/43 (0%)		1/39 (2.6%)		0/50 (0%)		0/50 (0%)		0/48 (0%)
Infections and infestations
Abscess limb	0/39 (0%)		0/43 (0%)		0/39 (0%)		1/50 (2%)		0/48 (0%)		0/48 (0%)
Appendicitis	0/39 (0%)		0/43 (0%)		0/39 (0%)		0/50 (0%)		0/50 (0%)		1/48 (2.1%)
Epididymitis	1/39 (2.6%)		0/43 (0%)		0/39 (0%)		0/50 (0%)		0/50 (0%)		0/48 (0%)
Pneumonia bacterial	0/39 (0%)		1/43 (2.3%)		0/39 (0%)		0/50 (0%)		0/50 (0%)		0/48 (0%)
Injury, poisoning and procedural complications
Humerus fracture	0/39 (0%)		0/43 (0%)		0/39 (0%)		0/50 (0%)		1/50 (2%)		0/48 (0%)
Subdural haematoma	0/39 (0%)		0/43 (0%)		0/39 (0%)		0/50 (0%)		0/50 (0%)		1/48 (2.1%)
Nervous system disorders
Cerebral haematoma	0/39 (0%)		0/43 (0%)		0/39 (0%)		0/50 (0%)		0/50 (0%)		1/48 (2.1%)
Respiratory, thoracic and mediastinal disorders
Haemothorax	0/39 (0%)		0/43 (0%)		0/39 (0%)		0/50 (0%)		0/50 (0%)		1/48 (2.1%)
Other (Not Including Serious) Adverse Events
	Placebo		Tofa 10 mg		PF-06650833 20 mg		PF-06650833 60 mg		PF-06650833 200 mg		PF-06650833 400 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/39 (25.6%)		8/43 (18.6%)		12/39 (30.8%)		11/50 (22%)		9/50 (18%)		11/48 (22.9%)
Gastrointestinal disorders
Abdominal pain upper	0/39 (0%)		1/43 (2.3%)		2/39 (5.1%)		0/50 (0%)		1/50 (2%)		0/48 (0%)
Abdominal Pain	2/39 (5.1%)		0/43 (0%)		0/39 (0%)		0/50 (0%)		1/50 (2%)		1/48 (2.1%)
Nausea	0/39 (0%)		1/43 (2.3%)		1/39 (2.6%)		4/50 (8%)		2/50 (4%)		1/48 (2.1%)
Infections and infestations
Upper respiratory tract infection	1/39 (2.6%)		2/43 (4.7%)		2/39 (5.1%)		0/50 (0%)		2/50 (4%)		3/48 (6.3%)
Nasopharyngitis	2/39 (5.1%)		3/43 (7%)		4/39 (10.3%)		2/50 (4%)		1/50 (2%)		2/48 (4.2%)
Investigations
Alanine aminotransferase increased	2/39 (5.1%)		1/43 (2.3%)		0/39 (0%)		1/50 (2%)		2/50 (4%)		1/48 (2.1%)
Musculoskeletal and connective tissue disorders
Rheumatoid arthritis	2/39 (5.1%)		2/43 (4.7%)		4/39 (10.3%)		2/50 (4%)		1/50 (2%)		3/48 (6.3%)
Nervous system disorders
Headache	2/39 (5.1%)		0/43 (0%)		1/39 (2.6%)		3/50 (6%)		0/50 (0%)		1/48 (2.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.