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Clinical Trial Results:
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

Summary
EudraCT number	2016-002337-30
Trial protocol	BG DE HU CZ SK ES HR
Global end of trial date	15 Aug 2018

Results information
Results version number	v1(current)
This version publication date	21 Aug 2019
First version publication date	21 Aug 2019
Other versions

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

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Trial information

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Sponsor protocol code

B7921005

ISRCTN number

US NCT number

NCT02996500

WHO universal trial number (UTN)

Sponsor organisation name

Pfizer, Inc.

Sponsor organisation address

235 E 42nd Street, New York, United States, NY 10017

Public contact

Pfizer ClinicalTrials.gov Call Center, Pfizer, Inc., +1 18007181021, ClinicalTrials.gov_Inquiries@pfizer.com

Scientific contact

Pfizer ClinicalTrials.gov Call Center, Pfizer, Inc., +1 18007181021, ClinicalTrials.gov_Inquiries@pfizer.com

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

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

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

Analysis stage

Final

Date of interim/final analysis

15 Jul 2019

Is this the analysis of the primary completion data?

Yes

Primary completion date

15 Aug 2018

Global end of trial reached?

Yes

Global end of trial date

15 Aug 2018

Was the trial ended prematurely?

Main objective of the trial

The primary objective of this study was to evaluate the efficacy of PF-06650833 at 12 weeks, in subjects with moderately severely active rheumatoid arthritis who had had an inadequate response to methotrexate.

Protection of trial subjects

This study was conducted in compliance with the ethical principles originating in or derived from the Declaration of Helsinki and in compliance with all International Council for Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. In addition, all local regulatory requirements were followed, in particular, those affording greater protection to the safety of trial subjects.

Background therapy

Evidence for comparator

Actual start date of recruitment

10 Nov 2016

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Korea, Republic of: 5

Country: Number of subjects enrolled

Mexico: 11

Country: Number of subjects enrolled

Poland: 37

Country: Number of subjects enrolled

Romania: 7

Country: Number of subjects enrolled

Russian Federation: 23

Country: Number of subjects enrolled

Serbia: 33

Country: Number of subjects enrolled

Slovakia: 12

Country: Number of subjects enrolled

Australia: 3

Country: Number of subjects enrolled

Bosnia and Herzegovina: 21

Country: Number of subjects enrolled

Bulgaria: 15

Country: Number of subjects enrolled

Croatia: 2

Country: Number of subjects enrolled

Czech Republic: 3

Country: Number of subjects enrolled

Georgia: 33

Country: Number of subjects enrolled

Germany: 3

Country: Number of subjects enrolled

Hungary: 17

Country: Number of subjects enrolled

Spain: 7

Country: Number of subjects enrolled

Taiwan: 3

Country: Number of subjects enrolled

Ukraine: 19

Country: Number of subjects enrolled

United States: 15

Worldwide total number of subjects

269

EEA total number of subjects

103

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

232

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

A total of 669 subjects were screened, 269 subjects were assigned to and treated with: placebo (39 subjects), PF-06650833 (187 subjects), or tofacitinib (43 subjects). Of the 269 subjects, 237 subjects completed the study.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Investigator, Assessor, Subject

Are arms mutually exclusive

Yes

Placebo

Arm description

Subjects 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.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Coated tablet

Routes of administration

Oral use

Dosage and administration details

Four matching PF-06650833 MR placebo tablets were administrated QD and 1 matching tofacitinib placebo tablet was administrated BID in 12 weeks treatment period.

Tofa 10 mg

Arm description

Subjects received 4 matching PF-06650833 MR placebo tablets QD and 1 tofacitinib 5 mg tablet BID in 12 weeks treatment period.

Arm type

Experimental

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Coated tablet

Routes of administration

Oral use

Dosage and administration details

Four matching PF-06650833 MR placebo tablets were administrated QD in 12 weeks treatment period.

Investigational medicinal product name

Tofacitinib

Investigational medicinal product code

Other name

Pharmaceutical forms

Coated tablet

Routes of administration

Oral use

Dosage and administration details

One tofacitinib 5 mg tablet was administrated BID in 12 weeks treatment period.

PF-06650833 20 mg

Arm description

Subjects 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.

Arm type

Experimental

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Coated tablet

Routes of administration

Oral use

Dosage and administration details

Three matching PF-06650833 MR placebo tablets were administrated QD and 1 matching tofacitinib placebo tablet was administrated BID in 12 weeks treatment period.

Investigational medicinal product name

PF-06650833

Investigational medicinal product code

Other name

Pharmaceutical forms

Coated tablet

Routes of administration

Oral use

Dosage and administration details

One MR tablet of PF-06650833 20 mg was administrated QD in 12 weeks treatment period.

PF-06650833 60 mg

Arm description

Subjects received 3 MR tablets of PF-06650833 20 mg and 1 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.

Arm type

Experimental

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Coated tablet

Routes of administration

Oral use

Dosage and administration details

One matching PF-06650833 MR placebo tablets was administrated QD and 1 matching tofacitinib placebo tablet was administrated BID in 12 weeks treatment period.

Investigational medicinal product name

PF-06650833

Investigational medicinal product code

Other name

Pharmaceutical forms

Coated tablet

Routes of administration

Oral use

Dosage and administration details

Three MR tablets of PF-06650833 20 mg were administrated QD in 12 weeks treatment period.

PF-06650833 200 mg

Arm description

Subjects 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.

Arm type

Experimental

Investigational medicinal product name

PF-06650833

Investigational medicinal product code

Other name

Pharmaceutical forms

Coated tablet

Routes of administration

Oral use

Dosage and administration details

Two MR tablets of PF-06650833 100 mg were administrated QD in 12 weeks treatment period.

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Coated tablet

Routes of administration

Oral use

Dosage and administration details

Two matching PF-06650833 MR placebo tablets were administrated QD and 1 matching tofacitinib placebo tablet was administrated BID in 12 weeks treatment period.

PF-06650833 400 mg

Arm description

Subjects received 4 MR tablets of PF-06650833 100 mg QD and 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.

Arm type

Experimental

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Coated tablet

Routes of administration

Oral use

Dosage and administration details

One matching tofacitinib placebo tablet was administrated BID in 12 weeks treatment period.

Investigational medicinal product name

PF-06650833

Investigational medicinal product code

Other name

Pharmaceutical forms

Coated tablet

Routes of administration

Oral use

Dosage and administration details

Four MR tablets of PF-06650833 100 mg were administrated QD in 12 weeks treatment period.

Number of subjects in period 1	Placebo	Tofa 10 mg	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Started	39	43	39	50	50	48
Completed	31	42	29	46	45	44
Not completed	8	1	10	4	5	4
Consent withdrawn by subject	3	-	3	-	2	-
Adverse event, non-fatal	1	1	4	3	1	2
Progressive Disease	1	-	-	-	-	-
Non-Compliance With Study Drug	-	-	-	-	-	1
Unspecified	2	-	2	-	-	-
Lost to follow-up	1	-	-	-	-	1
No Longer Meets Eligibility Criteria	-	-	1	-	-	-
Protocol deviation	-	-	-	1	-	-
Lack of efficacy	-	-	-	-	2	-

Baseline characteristics

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Reporting group title

Placebo

Reporting group description

Subjects 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.

Reporting group title

Tofa 10 mg

Reporting group description

Subjects received 4 matching PF-06650833 MR placebo tablets QD and 1 tofacitinib 5 mg tablet BID in 12 weeks treatment period.

Reporting group title

PF-06650833 20 mg

Reporting group description

Subjects 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.

Reporting group title

PF-06650833 60 mg

Reporting group description

Subjects received 3 MR tablets of PF-06650833 20 mg and 1 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.

Reporting group title

PF-06650833 200 mg

Reporting group description

Subjects 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.

Reporting group title

PF-06650833 400 mg

Reporting group description

Subjects received 4 MR tablets of PF-06650833 100 mg QD and 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.

Reporting group values	Placebo	Tofa 10 mg	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg	Total
Number of subjects	39	43	39	50	50	48	269
Age, Customized
Units: Subjects
In utero	0	0	0	0	0	0	0
Preterm newborn infants (gestational age <37 wks)	0	0	0	0	0	0	0
Newborns(0-27 days)	0	0	0	0	0	0	0
Infants and toddlers(28 days - 23 months)	0	0	0	0	0	0	0
Children(2-11 years)	0	0	0	0	0	0	0
Adolescents(12-17 years)	0	0	0	0	0	0	0
Adults(18-64 years)	33	38	32	44	43	42	232
Adults(65-84 years)	6	5	7	6	7	6	37
Adults(85 years and over)	0	0	0	0	0	0	0
Age Continuous
Units: Years
arithmetic mean (standard deviation)	54.9 ( 10.51 )	52.7 ( 10.02 )	55.9 ( 9.74 )	51.0 ( 12.05 )	53.6 ( 11.47 )	54.8 ( 8.76 )	-
Sex: Female, Male
Units: Subjects
Female	30	31	31	42	39	37	210
Male	9	12	8	8	11	11	59
Race/Ethnicity, Customized
Units: Subjects
White	37	43	37	47	47	43	254
Black or African American	0	0	0	0	0	0	0
Asian	2	0	1	1	2	2	8
American Indian or Alaska Native	0	0	0	1	1	0	2
Native Hawaiian or Other Pacific Islander	0	0	0	0	0	0	0
Other	0	0	1	1	0	3	5

End points

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Reporting group title

Placebo

Reporting group description

Subjects 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.

Reporting group title

Tofa 10 mg

Reporting group description

Subjects received 4 matching PF-06650833 MR placebo tablets QD and 1 tofacitinib 5 mg tablet BID in 12 weeks treatment period.

Reporting group title

PF-06650833 20 mg

Reporting group description

Subjects 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.

Reporting group title

PF-06650833 60 mg

Reporting group description

Subjects received 3 MR tablets of PF-06650833 20 mg and 1 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.

Reporting group title

PF-06650833 200 mg

Reporting group description

Subjects 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.

Reporting group title

PF-06650833 400 mg

Reporting group description

Subjects received 4 MR tablets of PF-06650833 100 mg QD and 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.

Primary: Change From Baseline in the Simplified Disease Activity Index (SDAI) at Week 12

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End point title

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

End point 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).

End point type

Primary

End point timeframe

Baseline and Week 12

Notes
[1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	Placebo	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Number of subjects analysed	34	30	45	44	45
Units: units on a scale
arithmetic mean (confidence interval 95%)
Week 12	-13.87 (-17.70 to -10.02)	-21.71 (-26.14 to -17.20)	-22.83 (-26.57 to -19.20)	-24.77 (-28.54 to -21.08)	-25.16 (-28.85 to -21.39)

Statistical Comparison in SDAI at Week 12

Statistical analysis description

Bayesian analysis of covariance (ANCOVA) modeling framework was used with baseline SDAI score as a covariate. The Confidence Interval was Credible Interval in this analysis.

Comparison groups

Placebo v PF-06650833 20 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.005

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

-7.83

Confidence interval

level

95%

sides

2-sided

lower limit

-13.73

upper limit

-1.97

Statistical Comparison in SDAI at Week 12

Statistical analysis description

Bayesian analysis of covariance (ANCOVA) modeling framework was used with baseline SDAI score as a covariate. The Confidence Interval was Credible Interval in this analysis.

Comparison groups

Placebo v PF-06650833 60 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

-8.96

Confidence interval

level

95%

sides

2-sided

lower limit

-14.37

upper limit

-3.66

Statistical Comparison in SDAI at Week 12

Statistical analysis description

Bayesian analysis of covariance (ANCOVA) modeling framework was used with baseline SDAI score as a covariate. The Confidence Interval was Credible Interval in this analysis.

Comparison groups

Placebo v PF-06650833 200 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

-10.89

Confidence interval

level

95%

sides

2-sided

lower limit

-16.36

upper limit

-5.63

Statistical Comparison in SDAI at Week 12

Statistical analysis description

Bayesian analysis of covariance (ANCOVA) modeling framework was used with baseline SDAI score as a covariate. The Confidence Interval was Credible Interval in this analysis.

Comparison groups

Placebo v PF-06650833 400 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

-11.29

Confidence interval

level

95%

sides

2-sided

lower limit

-16.62

upper limit

-5.92

Secondary: Change From Baseline in SDAI at Weeks 4 and 8

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End point title

Change From Baseline in SDAI at Weeks 4 and 8 ^[2]

End point description

End point type

Secondary

End point timeframe

Baseline, Weeks 4 and 8

Notes
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	Placebo	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Number of subjects analysed	39 ^[3]	39 ^[4]	50 ^[5]	50 ^[6]	48 ^[7]
Units: units on a scale
least squares mean (confidence interval 95%)
Week 4	-10.78 (-15.07 to -6.49)	-12.39 (-14.68 to -10.10)	-14.29 (-16.87 to -11.71)	-13.56 (-17.25 to -9.86)	-12.30 (-15.46 to -9.14)
Week 8	-17.07 (-22.58 to -11.55)	-16.62 (-20.71 to -12.53)	-18.85 (-22.03 to -15.67)	-19.95 (-24.81 to -15.08)	-21.15 (-25.50 to -16.79)

Notes
[3] - Number of Subjects Analyzed at Weeks 4 and 8: 37, 34
[4] - Number of Subjects Analyzed at Weeks 4 and 8: 37, 34
[5] - Number of Subjects Analyzed at Weeks 4 and 8: 49, 46
[6] - Number of Subjects Analyzed at Weeks 4 and 8: 47, 41
[7] - Number of Subjects Analyzed at Weeks 4 and 8: 47, 45

No statistical analyses for this end point

Secondary: Percentage of Subjects With SDAI Low Disease Activity Score (LDAS) (SDAI <=11) at Weeks 4, 8 and 12

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End point title

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

End point 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.

End point type

Secondary

End point timeframe

Weeks 4, 8 and 12

Notes
[8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	Placebo	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Number of subjects analysed	39 ^[9]	39 ^[10]	50 ^[11]	50 ^[12]	48 ^[13]
Units: percentage of subjects
number (confidence interval 95%)
Week 4	8.1 (0.0 to 16.9)	7.9 (0.0 to 16.5)	12.2 (3.1 to 21.4)	10.6 (1.8 to 19.5)	8.5 (0.5 to 16.5)
Week 8	14.7 (2.8 to 26.6)	20.0 (6.7 to 33.3)	17.4 (6.4 to 28.3)	29.3 (15.3 to 43.2)	33.3 (19.6 to 47.1)
Week 12	26.5 (11.6 to 41.3)	41.9 (24.6 to 59.3)	28.9 (15.6 to 42.1)	38.6 (24.2 to 53.0)	42.2 (27.8 to 56.7)

Notes
[9] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 37, 34, 34.
[10] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 38, 35, 31.
[11] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 49, 46, 45.
[12] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 47, 41, 44.
[13] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 47, 45, 45.

No statistical analyses for this end point

Secondary: Percentage of Subjects with SDAI Remission (SDAI <=3.3) at Weeks 4, 8 and 12

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End point title

Percentage of Subjects with SDAI Remission (SDAI <=3.3) at Weeks 4, 8 and 12 ^[14]

End point 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.

End point type

Secondary

End point timeframe

Weeks 4, 8 and 12

Notes
[14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	Placebo	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Number of subjects analysed	39 ^[15]	39 ^[16]	50 ^[17]	50 ^[18]	48 ^[19]
Units: percentage of subjects
number (confidence interval 95%)
Week 4	0 (0.0 to 0.0)	2.6 (0.0 to 7.7)	2.0 (0.0 to 6.0)	0 (0.0 to 0.0)	2.1 (0.0 to 6.3)
Week 8	0 (0.0 to 0.0)	8.6 (0.0 to 17.8)	0 (0.0 to 0.0)	7.3 (0.0 to 15.3)	2.2 (0.0 to 6.5)
Week 12	2.9 (0.0 to 8.6)	3.2 (0.0 to 9.4)	2.2 (0.0 to 6.5)	6.8 (0.0 to 14.3)	8.9 (0.6 to 17.2)

Notes
[15] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 37, 34, 34.
[16] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 38, 35, 31.
[17] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 49, 46, 45.
[18] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 47, 41, 44.
[19] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 47, 45, 45.

No statistical analyses for this end point

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

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End point title

Percentage of Subjects with Disease Activity Score-28 (4 Components Based on Erythrocyte Sedimentation Rate) (DAS28-4 [ESR]) LDAS (DAS28 <3.2) at Weeks 4, 8, and 12 ^[20]

End point 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. The criterion of DAS28-4 LDAS was DAS28<3.2.

End point type

Secondary

End point timeframe

Weeks 4, 8 and 12

Notes
[20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	Placebo	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Number of subjects analysed	39 ^[21]	39 ^[22]	50 ^[23]	50 ^[24]	48 ^[25]
Units: percentage of subjects
number (confidence interval 95%)
Week 4	2.9 (0.0 to 8.4)	8.1 (0.0 to 16.9)	6.4 (0.0 to 13.4)	8.3 (0.5 to 16.2)	4.3 (0.0 to 10.0)
Week 8	8.6 (0.0 to 17.8)	17.1 (4.7 to 29.6)	13.6 (3.5 to 23.8)	13.3 (3.4 to 23.3)	12.8 (3.2 to 22.3)
Week 12	17.6 (4.8 to 30.5)	20.0 (5.7 to 34.3)	24.4 (11.9 to 37.0)	22.2 (10.1 to 34.4)	17.8 (6.6 to 28.9)

Notes
[21] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 35, 34, 34.
[22] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 37, 35, 30.
[23] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 47, 44, 45.
[24] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 48, 45, 45.
[25] - Number of Subjects Analyzed at Weeks 4, 8 and 12:47, 47, 45.

No statistical analyses for this end point

Secondary: Percentage of Subjects With DAS28-3 (ESR) LDAS (DAS28 <3.2) at Weeks 4, 8, and 12

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End point title

Percentage of Subjects With DAS28-3 (ESR) LDAS (DAS28 <3.2) at Weeks 4, 8, and 12 ^[26]

End point 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 [mg/L]*1.08 + 0.16. Higher score indicated more disease activity. The criterion of DAS28-3 LDAS was DAS28<3.2.

End point type

Secondary

End point timeframe

Weeks 4, 8 and 12

Notes
[26] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	Placebo	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Number of subjects analysed	39 ^[27]	39 ^[28]	50 ^[29]	50 ^[30]	48 ^[31]
Units: percentage of subjects
number (confidence interval 95%)
Week 4	5.7 (0.0 to 13.4)	8.1 (0.0 to 16.9)	10.6 (1.8 to 19.5)	8.3 (0.5 to 16.2)	4.3 (0.0 to 10.0)
Week 8	8.6 (0.0 to 17.8)	20.0 (6.7 to 33.3)	15.9 (5.1 to 26.7)	8.9 (0.6 to 17.2)	14.9 (4.7 to 25.1)
Week 12	20.6 (7.0 to 34.2)	20.0 (5.7 to 34.3)	22.2 (10.1 to 34.4)	22.2 (10.1 to 34.4)	15.6 (5.0 to 26.1)

Notes
[27] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 35, 35, 34.
[28] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 37, 35, 30.
[29] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 47, 44, 45.
[30] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 48, 45, 45.
[31] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 47, 47, 45.

No statistical analyses for this end point

Secondary: Percentage of Subjects with Disease Activity Score-28 (4 Components Based on High-Sensitivity C-Reactive Protein) (DAS28-4 [CRP]) LDAS (DAS28 <3.2) at Weeks 4, 8, and 12

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End point title

Percentage of Subjects with Disease Activity Score-28 (4 Components Based on High-Sensitivity C-Reactive Protein) (DAS28-4 [CRP]) LDAS (DAS28 <3.2) at Weeks 4, 8, and 12 ^[32]

End point 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. Higher score indicated more disease activity. The possible lowest score is 0.96. The possible highest score is difficult to be determined, due to indeterminable nature of hs-CRP level; assuming hs-CRP level is 0 to 500 mg/L, the possible highest score would be 6.8 (when hs-CRP is 0) to 9.04 (when hs-CRP is 500 mg/L). The criterion of DAS28-4 LDAS was DAS28<3.2.

End point type

Secondary

End point timeframe

Weeks 4, 8 and 12

Notes
[32] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	Placebo	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Number of subjects analysed	39 ^[33]	39 ^[34]	50 ^[35]	50 ^[36]	48 ^[37]
Units: percentage of subjects
number (confidence interval 95%)
Week 4	8.1 (0.0 to 16.9)	13.2 (2.4 to 23.9)	16.3 (6.0 to 26.7)	12.8 (3.2 to 22.3)	8.5 (0.5 to 16.5)
Week 8	11.8 (0.9 to 22.6)	20.0 (6.7 to 33.3)	19.6 (8.1 to 31.0)	26.8 (13.3 to 40.4)	33.3 (19.6 to 47.1)
Week 12	20.6 (7.0 to 34.2)	38.7 (21.6 to 55.9)	35.6 (21.6 to 49.5)	40.9 (26.4 to 55.4)	42.2 (27.8 to 56.7)

Notes
[33] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 37, 34, 34.
[34] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 38, 35, 31.
[35] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 49, 46, 45.
[36] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 47, 41, 44.
[37] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 47, 45, 45.

No statistical analyses for this end point

Secondary: Percentage of Subjects With DAS28-3 (CRP) LDAS (DAS28 <3.2) at Weeks 4, 8, and 12

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End point title

Percentage of Subjects With DAS28-3 (CRP) LDAS (DAS28 <3.2) at Weeks 4, 8, and 12 ^[38]

End point 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. Higher score indicated more disease activity. The possible lowest score is 0.96. The possible highest score is difficult to be determined, due to indeterminable nature of hs-CRP level; assuming hs-CRP level is 0 to 500 mg/L, the possible highest score would be 6.8 (when hs-CRP is 0) to 9.04 (when hs-CRP is 500 mg/L). The criterion of DAS28-3 LDAS was DAS28<3.2.

End point type

Secondary

End point timeframe

Weeks 4, 8 and 12

Notes
[38] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	Placebo	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Number of subjects analysed	39 ^[39]	39 ^[40]	50 ^[41]	50 ^[42]	48 ^[43]
Units: percentage of subjects
number (confidence interval 95%)
Week 4	8.1 (0.0 to 16.9)	10.5 (0.8 to 20.3)	16.3 (6.0 to 26.7)	17.0 (6.3 to 27.8)	10.6 (1.8 to 19.5)
Week 8	20.6 (7.0 to 34.2)	22.9 (8.9 to 36.8)	19.6 (8.1 to 31.0)	34.1 (19.6 to 48.7)	37.8 (23.6 to 51.9)
Week 12	23.5 (9.3 to 37.8)	41.9 (24.6 to 59.3)	40.0 (25.7 to 54.3)	47.7 (33.0 to 62.5)	42.2 (27.8 to 56.7)

Notes
[39] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 37, 34, 34.
[40] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 38, 35, 31.
[41] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 49, 46, 45.
[42] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 47, 41, 44.
[43] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 47, 45, 45.

No statistical analyses for this end point

Secondary: Percentage of Subjects With DAS28-4 (ESR) Remission (DAS28 <2.6) at Weeks 4, 8 and 12

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End point title

Percentage of Subjects With DAS28-4 (ESR) Remission (DAS28 <2.6) at Weeks 4, 8 and 12 ^[44]

End point 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 [mg/L] + 0.014 (PtGA [mm]). Higher score indicated more disease activity. The criterion of DAS28-4 remission was DAS28<2.6.

End point type

Secondary

End point timeframe

Weeks 4, 8 and 12

Notes
[44] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	Placebo	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Number of subjects analysed	39 ^[45]	39 ^[46]	50 ^[47]	50 ^[48]	48 ^[49]
Units: percentage of subjects
number (confidence interval 95%)
Week 4	0 (0.0 to 0.0)	5.4 (0.0 to 12.7)	2.1 (0.0 to 6.3)	8.3 (0.5 to 16.2)	2.1 (0.0 to 6.3)
Week 8	5.7 (0.0 to 13.4)	11.4 (0.9 to 22.0)	9.1 (0.6 to 17.6)	6.7 (0.0 to 14.0)	10.6 (1.8 to 19.5)
Week 12	5.9 (0.0 to 13.8)	16.7 (3.3 to 30.0)	13.3 (3.4 to 23.3)	8.9 (0.6 to 17.2)	11.1 (1.9 to 20.3)

Notes
[45] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 35, 35, 34.
[46] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 37, 35, 30.
[47] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 47, 44, 45.
[48] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 48, 45, 45.
[49] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 47, 47, 45.

No statistical analyses for this end point

Secondary: Percentage of Subjects With DAS28-3 (ESR) Remission (DAS28 <2.6) at Weeks 4, 8 and 12

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End point title

Percentage of Subjects With DAS28-3 (ESR) Remission (DAS28 <2.6) at Weeks 4, 8 and 12 ^[50]

End point description

End point type

Secondary

End point timeframe

Weeks 4, 8 and 12

Notes
[50] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	Placebo	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Number of subjects analysed	39 ^[51]	39 ^[52]	50 ^[53]	50 ^[54]	48 ^[55]
Units: percentage of subjects
number (confidence interval 95%)
Week 4	0 (0.0 to 0.0)	2.7 (0.0 to 7.9)	2.1 (0.0 to 6.3)	6.3 (0.0 to 13.1)	2.1 (0.0 to 6.3)
Week 8	2.9 (0.0 to 8.4)	8.6 (0.0 to 17.8)	9.1 (0.6 to 17.6)	6.7 (0.0 to 14.0)	8.5 (0.5 to 16.5)
Week 12	8.8 (0.0 to 18.4)	10.0 (0.0 to 20.7)	13.3 (3.4 to 23.3)	11.1 (1.9 to 20.3)	8.9 (0.6 to 17.2)

Notes
[51] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 35, 35, 34.
[52] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 37, 35, 30.
[53] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 47, 44, 45.
[54] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 48, 45, 45.
[55] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 47, 47, 45.

No statistical analyses for this end point

Secondary: Percentage of Subjects With DAS28-4 (CRP) Remission (DAS28 <2.6) at Weeks 4, 8 and 12

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End point title

Percentage of Subjects With DAS28-4 (CRP) Remission (DAS28 <2.6) at Weeks 4, 8 and 12 ^[56]

End point description

End point type

Secondary

End point timeframe

Weeks 4, 8 and 12

Notes
[56] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	Placebo	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Number of subjects analysed	39 ^[57]	39 ^[58]	50 ^[59]	50 ^[60]	48 ^[61]
Units: percentage of subjects
number (confidence interval 95%)
Week 4	2.7 (0.0 to 7.9)	5.3 (0.0 to 12.4)	8.2 (0.5 to 15.8)	10.6 (1.8 to 19.5)	6.4 (0.0 to 13.4)
Week 8	8.8 (0.0 to 18.4)	17.1 (4.7 to 29.6)	10.9 (1.9 to 19.9)	22.0 (9.3 to 34.6)	13.3 (3.4 to 23.3)
Week 12	14.7 (2.8 to 26.6)	22.6 (7.9 to 37.3)	17.8 (6.6 to 28.9)	25.0 (12.2 to 37.8)	24.4 (11.9 to 37.0)

Notes
[57] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 37, 34, 34.
[58] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 38, 35, 31.
[59] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 49, 46, 45.
[60] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 47, 41, 44.
[61] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 47, 45, 45.

No statistical analyses for this end point

Secondary: Percentage of Subjects With DAS28-3 (CRP) Remission (DAS28 <2.6) at Weeks 4, 8 and 12

Top of page

End point title

Percentage of Subjects With DAS28-3 (CRP) Remission (DAS28 <2.6) at Weeks 4, 8 and 12 ^[62]

End point 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. Higher score indicated more disease activity. The possible lowest score is 1.15. The possible highest score is difficult to be determined, due to indeterminable nature of hs-CRP level. The criterion of DAS28-3 remission was DAS28<2.6.

End point type

Secondary

End point timeframe

Weeks 4, 8 and 12

Notes
[62] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	Placebo	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Number of subjects analysed	39 ^[63]	39 ^[64]	50 ^[65]	50 ^[66]	48 ^[67]
Units: percentage of subjects
number (confidence interval 95%)
Week 4	5.4 (0.0 to 12.7)	5.3 (0.0 to 12.4)	10.2 (1.7 to 18.7)	8.5 (0.5 to 16.5)	4.3 (0.0 to 10.0)
Week 8	8.8 (0.0 to 18.4)	14.3 (2.7 to 25.9)	10.9 (1.9 to 19.9)	22.0 (9.3 to 34.6)	13.3 (3.4 to 23.3)
Week 12	11.8 (0.9 to 22.6)	25.8 (10.4 to 41.2)	22.2 (10.1 to 34.4)	22.7 (10.3 to 35.1)	22.2 (10.1 to 34.4)

Notes
[63] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 37, 34, 34.
[64] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 38, 35, 31.
[65] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 49, 46, 45.
[66] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 47, 41, 44.
[67] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 47, 45, 45.

No statistical analyses for this end point

Secondary: Change From Baseline in DAS28-4 (ESR) at Weeks 4, 8 and 12

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End point title

Change From Baseline in DAS28-4 (ESR) at Weeks 4, 8 and 12 ^[68]

End point description

End point type

Secondary

End point timeframe

Baseline, Weeks 4, 8 and 12

Notes
[68] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	Placebo	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Number of subjects analysed	39 ^[69]	39 ^[70]	50 ^[71]	50 ^[72]	48 ^[73]
Units: units on a scale
least squares mean (confidence interval 95%)
Week 4	-0.80 (-1.13 to -0.47)	-1.15 (-1.47 to -0.82)	-1.35 (-1.64 to -1.07)	-1.14 (-1.42 to -0.86)	-1.13 (-1.42 to -0.84)
Week 8	-1.38 (-1.80 to -0.97)	-1.59 (-2.01 to -1.17)	-1.92 (-2.29 to -1.56)	-1.77 (-2.14 to -1.41)	-2.01 (-2.37 to -1.64)
Week 12	-1.55 (-1.97 to -1.13)	-1.85 (-2.28 to -1.41)	-2.37 (-2.74 to -2.01)	-2.23 (-2.60 to -1.86)	-2.36 (-2.73 to -1.99)

Notes
[69] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 35, 35, 34.
[70] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 37, 35, 30.
[71] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 47, 44, 45.
[72] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 48, 45, 45.
[73] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 47, 47, 45.

No statistical analyses for this end point

Secondary: Change From Baseline in DAS28-3 (ESR) at Weeks 4, 8 and 12

Top of page

End point title

Change From Baseline in DAS28-3 (ESR) at Weeks 4, 8 and 12 ^[74]

End point 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. Higher score indicated more disease activity.

End point type

Secondary

End point timeframe

Baseline, Weeks 4, 8 and 12

Notes
[74] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	Placebo	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Number of subjects analysed	39 ^[75]	39 ^[76]	50 ^[77]	50 ^[78]	48 ^[79]
Units: units on a scale
least squares mean (confidence interval 95%)
Week 4	-0.69 (-1.01 to -0.38)	-1.08 (-1.39 to -0.77)	-1.25 (-1.52 to -0.97)	-1.08 (-1.35 to -0.80)	-1.02 (-1.29 to -0.74)
Week 8	-1.14 (-1.54 to -0.75)	-1.52 (-1.92 to -1.12)	-1.80 (-2.15 to -1.45)	-1.62 (-1.97 to -1.27)	-1.79 (-2.14 to -1.44)
Week 12	-1.31 (-1.71 to -0.92)	-1.69 (-2.09 to -1.28)	-2.26 (-2.60 to -1.91)	-2.05 (-2.40 to -1.71)	-2.04 (-2.38 to -1.69)

Notes
[75] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 35, 35, 34.
[76] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 37, 35, 30.
[77] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 47, 44, 45.
[78] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 48, 45, 45.
[79] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 47, 47, 45.

No statistical analyses for this end point

Secondary: Change From Baseline in DAS28-4 (CRP) at Weeks 4, 8 and 12

Top of page

End point title

Change From Baseline in DAS28-4 (CRP) at Weeks 4, 8 and 12 ^[80]

End point 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 PGtA. 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 (PGtA [mm]) + 0.96. Higher score indicated more disease activity. The possible lowest score is 0.96. The possible highest score is difficult to be determined, due to indeterminable nature of hs-CRP level; assuming hs-CRP level is 0 to 500 mg/L, the possible highest score would be 6.8 (when hs-CRP is 0) to 9.04 (when hs-CRP is 500 mg/L).

End point type

Secondary

End point timeframe

Baseline, Weeks 4, 8 and 12

Notes
[80] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	Placebo	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Number of subjects analysed	39 ^[81]	39 ^[82]	50 ^[83]	50 ^[84]	48 ^[85]
Units: units on a scale
least squares mean (confidence interval 95%)
Week 4	-0.72 (-1.02 to -0.42)	-0.99 (-1.29 to -0.69)	-1.21 (-1.47 to -0.94)	-1.08 (-1.34 to -0.81)	-0.99 (-1.25 to -0.72)
Week 8	-1.20 (-1.58 to -0.83)	-1.31 (-1.68 to -0.94)	-1.59 (-1.92 to -1.27)	-1.65 (-1.98 to -1.32)	-1.73 (-2.06 to -1.40)
Week 12	-1.38 (-1.78 to -0.97)	-1.67 (-2.08 to -1.26)	-1.94 (-2.29 to -1.59)	-2.00 (-2.36 to -1.65)	-2.12 (-2.47 to -1.77)

Notes
[81] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 37, 34, 34.
[82] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 38, 35, 31.
[83] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 49, 46, 45.
[84] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 47, 41, 44.
[85] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 47, 45, 45.

No statistical analyses for this end point

Secondary: Change From Baseline in DAS28-3 (CRP) at Weeks 4, 8 and 12

Top of page

End point title

Change From Baseline in DAS28-3 (CRP) at Weeks 4, 8 and 12 ^[86]

End point description

End point type

Secondary

End point timeframe

Baseline, Weeks 4, 8 and 12

Notes
[86] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	Placebo	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Number of subjects analysed	39 ^[87]	39 ^[88]	50 ^[89]	50 ^[90]	48 ^[91]
Units: units on a scale
least squares mean (confidence interval 95%)
Week 4	-0.61 (-0.90 to -0.32)	-0.93 (-1.22 to -0.64)	-1.09 (-1.35 to -0.84)	-1.01 (-1.27 to -0.76)	-0.88 (-1.14 to -0.62)
Week 8	-0.97 (-1.32 to -0.61)	-1.24 (-1.60 to -0.89)	-1.46 (-1.76 to -1.15)	-1.52 (-1.83 to -1.20)	-1.52 (-1.83 to -1.21)
Week 12	-1.14 (-1.52 to -0.77)	-1.53 (-1.91 to -1.15)	-1.82 (-2.14 to -1.50)	-1.83 (-2.51 to -1.50)	-1.82 (-2.51 to -1.50)

Notes
[87] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 37, 34, 34.
[88] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 38, 35, 31.
[89] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 49, 46, 45.
[90] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 47, 41, 44.
[91] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 47, 45, 45.

No statistical analyses for this end point

Secondary: Percentage of Subjects Achieving American College of Rheumatology 20% (ACR20) Response at Weeks 4, 8 and 12

Top of page

End point title

Percentage of Subjects Achieving American College of Rheumatology 20% (ACR20) Response at Weeks 4, 8 and 12 ^[92]

End point 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.

End point type

Secondary

End point timeframe

Weeks 4, 8 and 12

Notes
[92] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	Placebo	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Number of subjects analysed	39 ^[93]	39 ^[94]	50 ^[95]	50 ^[96]	48 ^[97]
Units: percentage of subjects
number (confidence interval 95%)
Week 4	30.8 (16.3 to 45.3)	35.9 (20.8 to 51.0)	42.0 (28.3 to 55.7)	40.0 (26.4 to 53.6)	37.5 (23.8 to 51.2)
Week 8	46.2 (30.5 to 61.8)	51.3 (35.6 to 67.0)	58.0 (44.3 to 71.7)	52.0 (38.2 to 65.8)	64.6 (51.1 to 78.1)
Week 12	51.3 (35.6 to 67.0)	48.7 (33.0 to 64.4)	66.0 (52.9 to 79.1)	62.0 (48.5 to 75.5)	70.8 (58.0 to 83.7)

Notes
[93] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 39, 39, 39.
[94] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 39, 39, 39.
[95] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 50, 50, 50.
[96] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 50, 50, 50.
[97] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 48, 48, 48.

No statistical analyses for this end point

Secondary: Percentage of Subjects Achieving American College of Rheumatology 50% (ACR50) Response at Weeks 4, 8 and 12

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End point title

Percentage of Subjects Achieving American College of Rheumatology 50% (ACR50) Response at Weeks 4, 8 and 12 ^[98]

End point 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.

End point type

Secondary

End point timeframe

Weeks 4, 8 and 12

Notes
[98] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	Placebo	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Number of subjects analysed	39 ^[99]	39 ^[100]	50 ^[101]	50 ^[102]	48 ^[103]
Units: percentage of subjects
number (confidence interval 95%)
Week 4	2.6 (0.0 to 7.5)	10.3 (0.7 to 19.8)	6.0 (0.0 to 12.6)	6.0 (0.0 to 12.6)	8.3 (0.5 to 16.2)
Week 8	12.8 (2.3 to 23.3)	23.1 (9.9 to 36.3)	14.0 (4.4 to 23.6)	22.0 (10.5 to 33.5)	35.4 (21.9 to 48.9)
Week 12	20.5 (7.8 to 33.2)	25.6 (11.9 to 39.3)	22.0 (10.5 to 33.5)	40.0 (26.4 to 53.6)	43.8 (29.7 to 57.8)

Notes
[99] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 39, 39, 39.
[100] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 39, 39, 39.
[101] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 50, 50, 50.
[102] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 50, 50, 50.
[103] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 48, 48, 48.

No statistical analyses for this end point

Secondary: Percentage of Subjects Achieving American College of Rheumatology 70% (ACR70) Response at Weeks 4, 8 and 12

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End point title

Percentage of Subjects Achieving American College of Rheumatology 70% (ACR70) Response at Weeks 4, 8 and 12 ^[104]

End point 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.

End point type

Secondary

End point timeframe

Weeks 4, 8 and 12

Notes
[104] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	Placebo	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Number of subjects analysed	39 ^[105]	39 ^[106]	50 ^[107]	50 ^[108]	48 ^[109]
Units: percentage of subjects
number (confidence interval 95%)
Week 4	0.0 (0.0 to 0.0)	5.1 (0.0 to 12.1)	0.0 (0.0 to 0.0)	0.0 (0.0 to 0.0)	4.2 (0.0 to 9.8)
Week 8	2.6 (0.0 to 7.5)	10.3 (0.7 to 19.8)	0.0 (0.0 to 0.0)	10.0 (1.7 to 18.3)	6.3 (0.0 to 13.1)
Week 12	5.1 (0.0 to 12.1)	7.7 (0.0 to 16.1)	6.0 (0.0 to 12.6)	14.0 (4.4 to 23.6)	10.4 (1.8 to 19.1)

Notes
[105] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 39, 39, 39.
[106] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 39, 39, 39.
[107] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 50, 50, 50.
[108] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 50, 50, 50.
[109] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 48, 48, 48.

No statistical analyses for this end point

Secondary: Change From Baseline in the Tender/Painful and Swollen Joint Counts at Weeks 4, 8 and 12

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End point title

Change From Baseline in the Tender/Painful and Swollen Joint Counts at Weeks 4, 8 and 12 ^[110]

End point description

The TJC (28) included the following joints: shoulders, elbows, wrists, metacarpophalangeal (MCP) joints, proximal interphalangeal (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, metacarpophalangeals, thumb interphalangeal, proximal interphalangeals, and distal interphalangeals; lower extremity including 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.

End point type

Secondary

End point timeframe

Baseline, Weeks 4, 8 and 12

Notes
[110] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	Placebo	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Number of subjects analysed	39 ^[111]	39 ^[112]	50 ^[113]	50 ^[114]	48 ^[115]
Units: joints
arithmetic mean (standard deviation)
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 )

Notes
[111] - Number of Subjects Analyzed at Weeks 4, 8 and 12: 37, 35, 34.
[112] - Number of Subjects Analyzed at Weeks 4, 8 and 12:38, 35, 31.
[113] - Number of Subjects Analyzed at Weeks 4, 8 and 12:49, 46, 45.
[114] - Number of Subjects Analyzed at Weeks 4, 8 and 12:49, 46, 45.
[115] - Number of Subjects Analyzed at Weeks 4, 8 and 12:47, 47, 45.

No statistical analyses for this end point

Secondary: Change From Baseline in High-Sensitivity C-Reactive Protein (hs-CRP) at Weeks 4, 8 and 12

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End point title

Change From Baseline in High-Sensitivity C-Reactive Protein (hs-CRP) at Weeks 4, 8 and 12 ^[116]

End point description

Serum samples were analyzed to determine the level of hs-CRP, which was an acute-phase reactant.

End point type

Secondary

End point timeframe

Baseline, Weeks 4, 8 and 12

Notes
[116] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	Placebo	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Number of subjects analysed	39 ^[117]	39 ^[118]	50 ^[119]	50 ^[120]	48 ^[121]
Units: mg/dL
least squares mean (confidence interval 95%)
Week 4	0.22 (-0.17 to 0.60)	-0.15 (-0.53 to 0.23)	-0.66 (-1.00 to -0.32)	-0.66 (-1.00 to -0.32)	-0.65 (-1.00 to -0.31)
Week 8	0.12 (-0.35 to 0.59)	0.07 (-0.39 to 0.53)	-0.91 (-1.31 to -0.50)	-0.62 (-1.04 to -0.20)	-0.61 (-1.02 to -0.20)
Week 12	-0.07 (-0.54 to 0.39)	-0.23 (-0.71 to 0.25)	-0.74 (-1.14 to -0.34)	-0.68 (-1.09 to -0.27)	-0.64 (-1.04 to -0.23)

Notes
[117] - Number of Subjects Analyzed at Weeks 4, 8 and 12:37, 34, 34.
[118] - Number of Subjects Analyzed at Weeks 4, 8 and 12:38, 35, 31.
[119] - Number of Subjects Analyzed at Weeks 4, 8 and 12:49, 46, 46.
[120] - Number of Subjects Analyzed at Weeks 4, 8 and 12:47, 41, 44.
[121] - Number of Subjects Analyzed at Weeks 4, 8 and 12:47, 45, 45.

No statistical analyses for this end point

Secondary: Change From Baseline in the Physician’s Global Assessment of Arthritis (PhGA) at Weeks 4, 8, and 12

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End point title

Change From Baseline in the Physician’s Global Assessment of Arthritis (PhGA) at Weeks 4, 8, and 12 ^[122]

End point 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”.

End point type

Secondary

End point timeframe

Baseline, Weeks 4, 8 and 12

Notes
[122] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	Placebo	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Number of subjects analysed	39 ^[123]	39 ^[124]	50 ^[125]	50 ^[126]	48 ^[127]
Units: units on a scale
least squares mean (confidence interval 95%)
Week 4	-14.30 (-20.06 to -8.54)	-18.54 (-24.31 to -12.78)	-22.51 (-27.53 to -17.49)	-18.34 (-23.34 to -13.33)	-18.06 (-23.20 to -12.92)
Week 8	-25.86 (-32.11 to -19.62)	-26.80 (-33.12 to -20.48)	-27.76 (-33.21 to -22.31)	-27.86 (-33.31 to -22.42)	-29.97 (-35.42 to -24.52)
Week 12	-28.16 (-34.59 to -21.74)	-30.28 (-36.98 to -23.58)	-33.05 (-38.61 to -27.49)	-34.27 (-39.86 to -28.68)	-36.34 (-41.95 to -30.73)

Notes
[123] - Number of Subjects Analyzed at Weeks 4, 8 and 12:37, 35, 34.
[124] - Number of Subjects Analyzed at Weeks 4, 8 and 12:37, 34, 30.
[125] - Number of Subjects Analyzed at Weeks 4, 8 and 12:49, 46, 46.
[126] - Number of Subjects Analyzed at Weeks 4, 8 and 12:49, 46, 45.
[127] - Number of Subjects Analyzed at Weeks 4, 8 and 12:47, 47, 45.

No statistical analyses for this end point

Secondary: Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Treatment-Related TEAEs

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End point title

Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Treatment-Related TEAEs

End point 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.

End point type

Secondary

End point timeframe

Baseline up to primary completion date (PCD) (about 21 months)

End point values	Placebo	Tofa 10 mg	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Number of subjects analysed	39	43	39	50	50	48
Units: subjects
TEAEs (all causality)	17	17	20	27	19	23
TEAEs (treatment-related)	8	6	12	8	8	6
SAEs (all causality)	1	1	1	1	1	3
SAEs (treatment-related)	0	0	1	0	0	0

No statistical analyses for this end point

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

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End point title

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

End point description

Laboratory evaluation included hematology, clinical chemistry, and urinalysis. Each parameter was evaluated against commonly used and widely accepted criteria.

End point type

Secondary

End point timeframe

Baseline up to PCD (about 21 months)

End point values	Placebo	Tofa 10 mg	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Number of subjects analysed	38	43	39	50	50	48
Units: subjects	30	32	30	36	41	38

No statistical analyses for this end point

Secondary: Number of Subjects With Vital Signs Data Meeting Pre-sepcified Criteria

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End point title

Number of Subjects With Vital Signs Data Meeting Pre-sepcified Criteria

End point description

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

End point type

Secondary

End point timeframe

Baseline up to PCD (about 21 months)

End point values	Placebo	Tofa 10 mg	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Number of subjects analysed	38	43	39	50	49	48
Units: subjects
Sitting Diastolic BP < 50 mmHg	1	0	0	0	0	0
Sitting Pulse Rate < 40 bpm	0	0	0	0	0	0
Sitting Pulse Rate > 120 bpm	0	0	0	0	0	0
Sitting Systolic BP < 90 mmHg	0	0	0	0	0	0
Increase: Sitting Systolic BP Chg >= 30 mmHg	0	0	1	1	0	1
Increase: Sitting Diastolic BP Chg >= 20 mmHg	1	2	3	0	1	2
Decrease: Sitting Systolic BP Chg >= 30 mmHg	2	3	0	2	3	3
Decrease: Sitting Diastolic BP Chg >= 20 mmHg	2	4	2	4	3	2

No statistical analyses for this end point

Secondary: Number of Subjects With Electrocardiogram (ECG) Data Meeting Pre-sepcified Criteria

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End point title

Number of Subjects With Electrocardiogram (ECG) Data Meeting Pre-sepcified Criteria

End point 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 (QTc) using Fridericia’s formula (QTcF interval), and QTc calculated using Bazett’s correction factor (QTcB interval).

End point type

Secondary

End point timeframe

Baseline up to PCD (about 21 months)

End point values	Placebo	Tofa 10 mg	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Number of subjects analysed	38	43	39	50	49	48
Units: subjects
PR interval >=300 msec	0	0	0	0	0	0
QRS duration >=140 msec	0	0	0	0	0	0
QT interval >=500 msec	0	0	0	0	0	0
QTcB interval >=450 and <480 msec	5	4	5	4	5	13
QTcB interval >=480 and <500 msec	0	0	0	0	0	0
QTcB interval >=500 msec	0	0	0	0	0	0
QTcF interval >=450 and <480 msec	0	1	1	0	1	4
QTcF interval >=480 and <500 msec	0	0	0	0	0	0
QTcF interval >=500 msec	0	0	0	0	0	0
PR interval increase >=25/50%	0	0	0	0	1	0
QRS duration increase >=50%	0	0	0	0	0	0
QTcB interval increase >=30 and increase <60 msec	3	6	9	3	4	7
QTcB interval increase >=60 msec	0	0	0	0	0	0
QTcF interval increase >=30 and increase <60 msec	2	4	5	0	5	5
QTcF interval increase >=60 msec	0	0	0	0	0	0

No statistical analyses for this end point

Secondary: Number of Subjects With Urinalysis Data Meeting Pre-specified Criteria

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End point title

Number of Subjects With Urinalysis Data Meeting Pre-specified Criteria

End point 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.

End point type

Secondary

End point timeframe

Baseline up to PCD (about 21 months)

End point values	Placebo	Tofa 10 mg	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Number of subjects analysed	38	43	39	50	49	48
Units: subjects
Specific gravity <1.003	0	0	0	0	0	0
Specific gravity >1.030	3	0	0	3	2	2
pH <4.5	0	0	0	0	0	0
pH >8	0	0	0	0	0	0
Urine glucose >=1	0	0	4	2	2	2
Ketones >=1	3	0	1	2	1	1
Urine protein >=1	0	0	0	0	1	0
Urine hemoglobin >=1	7	5	6	5	12	6
Urobilinogen >=1	1	0	0	0	0	1
Urine bilirubin >=1	0	0	0	0	0	0
Nitrite >=1	3	5	3	1	9	11
Leukocyte esterase >=1	16	15	14	14	19	19
Urine erythrocytes(/HPF) >=20	1	2	3	1	3	3
Urine leukocytes (/HPF) >=20	4	3	2	2	7	7
Granular casts (/LPF) >1	1	1	0	0	0	0
Hyaline Casts (/LPF)	4	4	6	7	4	3
Bacteria >20	0	0	0	0	0	0
Atypical, needle-like crystals urine >=1	0	0	0	0	2	0

No statistical analyses for this end point

Secondary: Change From Baseline in the Patient’s Assessment of Arthritis Pain (PAAP) Visual Analogue Scale (VAS) at Weeks 4, 8, 12

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End point title

Change From Baseline in the Patient’s Assessment of Arthritis Pain (PAAP) Visual Analogue Scale (VAS) at Weeks 4, 8, 12 ^[128]

End point 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 subject had had extensive contact with site personnel and/or Investigator.

End point type

Secondary

End point timeframe

Baseline, Weeks 4, 8 and 12

Notes
[128] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	Placebo	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Number of subjects analysed	39 ^[129]	39 ^[130]	50 ^[131]	50 ^[132]	48 ^[133]
Units: units on a scale
arithmetic mean (standard deviation)
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 )	-31.8 ( 23.70 )

Notes
[129] - Number of Subjects Analyzed at Weeks 4, 8 and 12:37, 35, 34.
[130] - Number of Subjects Analyzed at Weeks 4, 8 and 12:38, 35, 31.
[131] - Number of Subjects Analyzed at Weeks 4, 8 and 12:49, 46, 46.
[132] - Number of Subjects Analyzed at Weeks 4, 8 and 12:49, 46, 45.
[133] - Number of Subjects Analyzed at Weeks 4, 8 and 12:47, 47, 45.

No statistical analyses for this end point

Secondary: Change From Baseline in the Patient Global Assessment of Arthritis (PtGA) VAS at Weeks 4, 8, 12

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End point title

Change From Baseline in the Patient Global Assessment of Arthritis (PtGA) VAS at Weeks 4, 8, 12 ^[134]

End point 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 subject had had extensive contact with site personnel and/or Investigator. The higher score indicated more severe disease.

End point type

Secondary

End point timeframe

Baseline, Weeks 4, 8 and 12

Notes
[134] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	Placebo	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Number of subjects analysed	39 ^[135]	39 ^[136]	49 ^[137]	50 ^[138]	48 ^[139]
Units: units on a scale
arithmetic mean (standard deviation)
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 )

Notes
[135] - Number of Subjects Analyzed at Weeks 4, 8 and 12:37, 35, 34.
[136] - Number of Subjects Analyzed at Weeks 4, 8 and 12:38, 35, 31.
[137] - Number of Subjects Analyzed at Weeks 4, 8 and 12:49, 46, 46.
[138] - Number of Subjects Analyzed at Weeks 4, 8 and 12:49, 46, 45.
[139] - Number of Subjects Analyzed at Weeks 4, 8 and 12:47, 47, 45.

No statistical analyses for this end point

Secondary: Change From Baseline in the Health Assessment Questionnaire – Disability Index (HAQ-DI) at Weeks 4, 8, and 12

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End point title

Change From Baseline in the Health Assessment Questionnaire – Disability Index (HAQ-DI) at Weeks 4, 8, and 12 ^[140]

End point description

The HAQ-DI assesses the degree of difficulty that a subject has experienced during the past week in 8 domains of daily living activities: dressing and grooming, arising, eating, walking, hygiene, reach, grip, and other activities. Each activity category consists of 2-3 items. For each question in the questionnaire, the level of difficulty is scored from 0 to 3 with 0 representing “no difficulty,” 1 as “some difficulty,” 2 as “much difficulty,” and 3 as “unable to do.” Any activity that requires assistance from another individual or requires the use of an assistive device adjusts to a minimum score of 2 to represent a more limited functional status. This questionnaire was performed early in the clinic visit and before the subject had had extensive contact with site personnel and/or Investigator.

End point type

Secondary

End point timeframe

Baseline Weeks 4, 8 and 12

Notes
[140] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	Placebo	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Number of subjects analysed	39 ^[141]	39 ^[142]	50 ^[143]	50 ^[144]	48 ^[145]
Units: units on a scale
arithmetic mean (standard deviation)
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 )

Notes
[141] - Number of Subjects Analyzed at Weeks 4, 8 and 12:37, 35, 34.
[142] - Number of Subjects Analyzed at Weeks 4, 8 and 12:38, 35, 31.
[143] - Number of Subjects Analyzed at Weeks 4, 8 and 12:49, 46, 46.
[144] - Number of Subjects Analyzed at Weeks 4, 8 and 12:49, 46, 45.
[145] - Number of Subjects Analyzed at Weeks 4, 8 and 12:47, 47, 45.

No statistical analyses for this end point

Secondary: Change From Baseline in the 36 Item Short Form Health Survey (SF-36) Version 2 (Acute) 8 Domain Scores at Week 12

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End point title

Change From Baseline in the 36 Item Short Form Health Survey (SF-36) Version 2 (Acute) 8 Domain Scores at Week 12 ^[146]

End point 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. This was performed early in the clinic visit and before the subject had had extensive contact with site personnel and/or Investigator.

End point type

Secondary

End point timeframe

Baseline and Week 12

Notes
[146] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	Placebo	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Number of subjects analysed	39 ^[147]	39 ^[148]	50 ^[149]	50 ^[150]	48 ^[151]
Units: units on a scale
arithmetic mean (standard deviation)
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 )

Notes
[147] - Number of Subjects Analyzed at Week 12: 34
[148] - Number of Subjects Analyzed at Week 12: 31
[149] - Number of Subjects Analyzed at Week 12: 46
[150] - Number of Subjects Analyzed at Week 12: 45
[151] - Number of Subjects Analyzed at Week 12: 45

No statistical analyses for this end point

Secondary: Change From Baseline in the Physical Component Score (PCS) and Mental Component Score (MCS) at Week 12

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End point title

Change From Baseline in the Physical Component Score (PCS) and Mental Component Score (MCS) at Week 12 ^[152]

End point 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). This was performed early in the clinic visit and before the subject had had extensive contact with site personnel and/or Investigator.

End point type

Secondary

End point timeframe

Baseline and Week 12

Notes
[152] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	Placebo	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Number of subjects analysed	39 ^[153]	39 ^[154]	50 ^[155]	50 ^[156]	48 ^[157]
Units: units on a scale
arithmetic mean (standard deviation)
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 )

Notes
[153] - Number of Subjects Analyzed at Week 12: 34
[154] - Number of Subjects Analyzed at Week 12: 31
[155] - Number of Subjects Analyzed at Week 12: 46
[156] - Number of Subjects Analyzed at Week 12: 45
[157] - Number of Subjects Analyzed at Week 12: 45

No statistical analyses for this end point

Secondary: Change From Baseline in the European Quality of Life 5 Dimensions-3 Level (EQ-5D-3L) Score at Week 12

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End point title

Change From Baseline in the European Quality of Life 5 Dimensions-3 Level (EQ-5D-3L) Score at Week 12 ^[158]

End point 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 rheumatoid arthritis (RA). This questionnaire was performed early in the clinic visit and before the subject had had extensive contact with site personnel and/or Investigator. The form was checked by site staff for completeness.

End point type

Secondary

End point timeframe

Baseline and Week 12

Notes
[158] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	Placebo	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Number of subjects analysed	39 ^[159]	39 ^[160]	50 ^[161]	50 ^[162]	48 ^[163]
Units: units on a scale
arithmetic mean (standard deviation)
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 )

Notes
[159] - Number of Subjects Analyzed at Week 12: 34
[160] - Number of Subjects Analyzed at Week 12: 31
[161] - Number of Subjects Analyzed at Week 12: 45
[162] - Number of Subjects Analyzed at Week 12: 45
[163] - Number of Subjects Analyzed at Week 12: 45

No statistical analyses for this end point

Secondary: Change From Baseline in the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Total Score at Week 12

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End point title

Change From Baseline in the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Total Score at Week 12 ^[164]

End point 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 subject has extensive contact with site personnel and/or investigator.

End point type

Secondary

End point timeframe

Baseline and Week 12

Notes
[164] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	Placebo	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Number of subjects analysed	39 ^[165]	39 ^[166]	50 ^[167]	50 ^[168]	48 ^[169]
Units: units on a scale
arithmetic mean (standard deviation)	8.4 ( 8.76 )	4.6 ( 10.92 )	6.8 ( 8.33 )	7.2 ( 11.45 )	9.5 ( 9.68 )

Notes
[165] - Number of Subjects Analyzed at Week 12: 34
[166] - Number of Subjects Analyzed at Week 12: 31
[167] - Number of Subjects Analyzed at Week 12: 46
[168] - Number of Subjects Analyzed at Week 12: 45
[169] - Number of Subjects Analyzed at Week 12: 45

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Baseline up to PCD (about 21 months)

Adverse event reporting additional description

The same event may appear as both an AE and a SAE. An event may be categorized as serious in 1 subject and as non-serious in another subject, or 1 subject may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of subjects evaluable for SAEs or AEs.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

21.0

Reporting group title

Placebo

Reporting group description

Subjects 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.

Reporting group title

Tofa 10 mg

Reporting group description

Subjects received 4 matching PF-06650833 MR placebo tablets QD and 1 tofacitinib 5 mg tablet BID in 12 weeks treatment period.

Reporting group title

PF-06650833 20 mg

Reporting group description

Subjects 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.

Reporting group title

PF-06650833 60 mg

Reporting group description

Subjects received 3 MR tablets of PF-06650833 20 mg and 1 matching PF-06650833 MR placebo tablets QD, 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.

Reporting group title

PF-06650833 200 mg

Reporting group description

Subjects 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.

Reporting group title

PF-06650833 400 mg

Reporting group description

Subjects received 4 MR tablets of PF- 06650833 100 mg QD and 1 matching tofacitinib placebo tablet BID in 12 weeks treatment period.

Serious adverse events	Placebo	Tofa 10 mg	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Total subjects affected by serious adverse events
subjects affected / exposed	1 / 39 (2.56%)	1 / 43 (2.33%)	1 / 39 (2.56%)	1 / 50 (2.00%)	1 / 50 (2.00%)	3 / 48 (6.25%)
number of deaths (all causes)	0	0	0	0	0	0
number of deaths resulting from adverse events
Injury, poisoning and procedural complications
Humerus fracture
subjects affected / exposed	0 / 39 (0.00%)	0 / 43 (0.00%)	0 / 39 (0.00%)	0 / 50 (0.00%)	1 / 50 (2.00%)	0 / 48 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Subdural haematoma
subjects affected / exposed	0 / 39 (0.00%)	0 / 43 (0.00%)	0 / 39 (0.00%)	0 / 50 (0.00%)	0 / 50 (0.00%)	1 / 48 (2.08%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Acute myocardial infarction
subjects affected / exposed	0 / 39 (0.00%)	0 / 43 (0.00%)	0 / 39 (0.00%)	0 / 50 (0.00%)	0 / 50 (0.00%)	1 / 48 (2.08%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Cerebral haematoma
subjects affected / exposed	0 / 39 (0.00%)	0 / 43 (0.00%)	0 / 39 (0.00%)	0 / 50 (0.00%)	0 / 50 (0.00%)	1 / 48 (2.08%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Hepatotoxicity
subjects affected / exposed	0 / 39 (0.00%)	0 / 43 (0.00%)	1 / 39 (2.56%)	0 / 50 (0.00%)	0 / 50 (0.00%)	0 / 48 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Haemothorax
subjects affected / exposed	0 / 39 (0.00%)	0 / 43 (0.00%)	0 / 39 (0.00%)	0 / 50 (0.00%)	0 / 50 (0.00%)	1 / 48 (2.08%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Abscess limb
subjects affected / exposed	0 / 39 (0.00%)	0 / 43 (0.00%)	0 / 39 (0.00%)	1 / 50 (2.00%)	0 / 50 (0.00%)	0 / 48 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Appendicitis
subjects affected / exposed	0 / 39 (0.00%)	0 / 43 (0.00%)	0 / 39 (0.00%)	0 / 50 (0.00%)	0 / 50 (0.00%)	1 / 48 (2.08%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Epididymitis
subjects affected / exposed	1 / 39 (2.56%)	0 / 43 (0.00%)	0 / 39 (0.00%)	0 / 50 (0.00%)	0 / 50 (0.00%)	0 / 48 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia bacterial
subjects affected / exposed	0 / 39 (0.00%)	1 / 43 (2.33%)	0 / 39 (0.00%)	0 / 50 (0.00%)	0 / 50 (0.00%)	0 / 48 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

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

Non-serious adverse events	Placebo	Tofa 10 mg	PF-06650833 20 mg	PF-06650833 60 mg	PF-06650833 200 mg	PF-06650833 400 mg
Total subjects affected by non serious adverse events
subjects affected / exposed	10 / 39 (25.64%)	8 / 43 (18.60%)	12 / 39 (30.77%)	11 / 50 (22.00%)	9 / 50 (18.00%)	11 / 48 (22.92%)
Investigations
Alanine aminotransferase increased
subjects affected / exposed	2 / 39 (5.13%)	1 / 43 (2.33%)	0 / 39 (0.00%)	1 / 50 (2.00%)	2 / 50 (4.00%)	1 / 48 (2.08%)
occurrences all number	2	1	0	1	3	1
Nervous system disorders
Headache
subjects affected / exposed	2 / 39 (5.13%)	0 / 43 (0.00%)	1 / 39 (2.56%)	3 / 50 (6.00%)	0 / 50 (0.00%)	1 / 48 (2.08%)
occurrences all number	2	0	1	3	0	1
Gastrointestinal disorders
Abdominal pain upper
subjects affected / exposed	0 / 39 (0.00%)	1 / 43 (2.33%)	2 / 39 (5.13%)	0 / 50 (0.00%)	1 / 50 (2.00%)	0 / 48 (0.00%)
occurrences all number	0	1	2	0	1	0
Abdominal Pain
subjects affected / exposed	2 / 39 (5.13%)	0 / 43 (0.00%)	0 / 39 (0.00%)	0 / 50 (0.00%)	1 / 50 (2.00%)	1 / 48 (2.08%)
occurrences all number	2	0	0	0	1	1
Nausea
subjects affected / exposed	0 / 39 (0.00%)	1 / 43 (2.33%)	1 / 39 (2.56%)	4 / 50 (8.00%)	2 / 50 (4.00%)	1 / 48 (2.08%)
occurrences all number	0	1	1	4	2	1
Musculoskeletal and connective tissue disorders
Rheumatoid arthritis
subjects affected / exposed	2 / 39 (5.13%)	2 / 43 (4.65%)	4 / 39 (10.26%)	2 / 50 (4.00%)	1 / 50 (2.00%)	3 / 48 (6.25%)
occurrences all number	2	2	4	2	1	3
Infections and infestations
Upper respiratory tract infection
subjects affected / exposed	1 / 39 (2.56%)	2 / 43 (4.65%)	2 / 39 (5.13%)	0 / 50 (0.00%)	2 / 50 (4.00%)	3 / 48 (6.25%)
occurrences all number	1	5	3	0	2	3
Nasopharyngitis
subjects affected / exposed	2 / 39 (5.13%)	3 / 43 (6.98%)	4 / 39 (10.26%)	2 / 50 (4.00%)	1 / 50 (2.00%)	2 / 48 (4.17%)
occurrences all number	2	3	4	2	1	3

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

04 Oct 2016

The protocol was amended in response to US regulatory feedback to increase the frequency of monitoring for urinary crystals and evidence of acute kidney injury by adding 3 study visits at Weeks 6, 10 and 14.

28 Nov 2016

The protocol was updated to allow prior (single) TNF experience after appropriate washout irrespective of inadequate response or due to lack of continued access; updated to clarify exclusion of subjects with alcohol or substance use and with prior active TB and to stipulate that live vaccines were not administered for at least 30 days after the last dose of study medication.

12 Jul 2017

Protocol summary and Sections 3, 4.1 and 5.7.1 were updated to clarify that prior use of parenteral MTX was permitted; Inclusion Criterion was updated to increase the recruitment age from 70 to 75 years old; Exclusion Criterion was updated to clarify TB and vaccination exclusion criteria, exclude recruitment of subjects with dermatomyositis and fibromyalgia, define the exclusion based on UACR as >=3 mg/mmol or >=30 mg/g, delete the subject eligibility based on the presence of atypical, needle like, urine crystals on urine microscopy.

08 Aug 2017

Protocol summary and section 3 were updated to clarify that methotrexate must have been dosed for at least 3 months to establish “inadequate response” not “lack of inadequate response; added the subject eligibility based on the presence of atypical, needle like, urine crystals on urine microscopy.

Were there any global interruptions to the trial? No

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

None reported

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Clinical trials

Clinical Trial Results: A 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

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Change From Baseline in the Simplified Disease Activity Index (SDAI) at Week 12

Primary: Change From Baseline in the Simplified Disease Activity Index (SDAI) at Week 12

Secondary: Change From Baseline in SDAI at Weeks 4 and 8

Secondary: Change From Baseline in SDAI at Weeks 4 and 8

Secondary: Percentage of Subjects With SDAI Low Disease Activity Score (LDAS) (SDAI <=11) at Weeks 4, 8 and 12

Secondary: Percentage of Subjects With SDAI Low Disease Activity Score (LDAS) (SDAI <=11) at Weeks 4, 8 and 12

Secondary: Percentage of Subjects with SDAI Remission (SDAI <=3.3) at Weeks 4, 8 and 12

Secondary: Percentage of Subjects with SDAI Remission (SDAI <=3.3) at Weeks 4, 8 and 12

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

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

Secondary: Percentage of Subjects With DAS28-3 (ESR) LDAS (DAS28 <3.2) at Weeks 4, 8, and 12

Secondary: Percentage of Subjects With DAS28-3 (ESR) LDAS (DAS28 <3.2) at Weeks 4, 8, and 12

Secondary: Percentage of Subjects with Disease Activity Score-28 (4 Components Based on High-Sensitivity C-Reactive Protein) (DAS28-4 [CRP]) LDAS (DAS28 <3.2) at Weeks 4, 8, and 12

Secondary: Percentage of Subjects with Disease Activity Score-28 (4 Components Based on High-Sensitivity C-Reactive Protein) (DAS28-4 [CRP]) LDAS (DAS28 <3.2) at Weeks 4, 8, and 12

Secondary: Percentage of Subjects With DAS28-3 (CRP) LDAS (DAS28 <3.2) at Weeks 4, 8, and 12

Secondary: Percentage of Subjects With DAS28-3 (CRP) LDAS (DAS28 <3.2) at Weeks 4, 8, and 12

Secondary: Percentage of Subjects With DAS28-4 (ESR) Remission (DAS28 <2.6) at Weeks 4, 8 and 12

Secondary: Percentage of Subjects With DAS28-4 (ESR) Remission (DAS28 <2.6) at Weeks 4, 8 and 12

Secondary: Percentage of Subjects With DAS28-3 (ESR) Remission (DAS28 <2.6) at Weeks 4, 8 and 12

Secondary: Percentage of Subjects With DAS28-3 (ESR) Remission (DAS28 <2.6) at Weeks 4, 8 and 12

Secondary: Percentage of Subjects With DAS28-4 (CRP) Remission (DAS28 <2.6) at Weeks 4, 8 and 12

Secondary: Percentage of Subjects With DAS28-4 (CRP) Remission (DAS28 <2.6) at Weeks 4, 8 and 12

Secondary: Percentage of Subjects With DAS28-3 (CRP) Remission (DAS28 <2.6) at Weeks 4, 8 and 12

Secondary: Percentage of Subjects With DAS28-3 (CRP) Remission (DAS28 <2.6) at Weeks 4, 8 and 12

Secondary: Change From Baseline in DAS28-4 (ESR) at Weeks 4, 8 and 12

Secondary: Change From Baseline in DAS28-4 (ESR) at Weeks 4, 8 and 12

Secondary: Change From Baseline in DAS28-3 (ESR) at Weeks 4, 8 and 12

Secondary: Change From Baseline in DAS28-3 (ESR) at Weeks 4, 8 and 12

Secondary: Change From Baseline in DAS28-4 (CRP) at Weeks 4, 8 and 12

Secondary: Change From Baseline in DAS28-4 (CRP) at Weeks 4, 8 and 12

Secondary: Change From Baseline in DAS28-3 (CRP) at Weeks 4, 8 and 12

Secondary: Change From Baseline in DAS28-3 (CRP) at Weeks 4, 8 and 12

Secondary: Percentage of Subjects Achieving American College of Rheumatology 20% (ACR20) Response at Weeks 4, 8 and 12

Secondary: Percentage of Subjects Achieving American College of Rheumatology 20% (ACR20) Response at Weeks 4, 8 and 12

Secondary: Percentage of Subjects Achieving American College of Rheumatology 50% (ACR50) Response at Weeks 4, 8 and 12

Secondary: Percentage of Subjects Achieving American College of Rheumatology 50% (ACR50) Response at Weeks 4, 8 and 12

Secondary: Percentage of Subjects Achieving American College of Rheumatology 70% (ACR70) Response at Weeks 4, 8 and 12

Secondary: Percentage of Subjects Achieving American College of Rheumatology 70% (ACR70) Response at Weeks 4, 8 and 12

Secondary: Change From Baseline in the Tender/Painful and Swollen Joint Counts at Weeks 4, 8 and 12

Secondary: Change From Baseline in the Tender/Painful and Swollen Joint Counts at Weeks 4, 8 and 12

Secondary: Change From Baseline in High-Sensitivity C-Reactive Protein (hs-CRP) at Weeks 4, 8 and 12

Secondary: Change From Baseline in High-Sensitivity C-Reactive Protein (hs-CRP) at Weeks 4, 8 and 12

Secondary: Change From Baseline in the Physician’s Global Assessment of Arthritis (PhGA) at Weeks 4, 8, and 12

Secondary: Change From Baseline in the Physician’s Global Assessment of Arthritis (PhGA) at Weeks 4, 8, and 12

Secondary: Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Treatment-Related TEAEs

Secondary: Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Treatment-Related TEAEs

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

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

Secondary: Number of Subjects With Vital Signs Data Meeting Pre-sepcified Criteria

Secondary: Number of Subjects With Vital Signs Data Meeting Pre-sepcified Criteria

Secondary: Number of Subjects With Electrocardiogram (ECG) Data Meeting Pre-sepcified Criteria

Secondary: Number of Subjects With Electrocardiogram (ECG) Data Meeting Pre-sepcified Criteria

Secondary: Number of Subjects With Urinalysis Data Meeting Pre-specified Criteria

Secondary: Number of Subjects With Urinalysis Data Meeting Pre-specified Criteria

Secondary: Change From Baseline in the Patient’s Assessment of Arthritis Pain (PAAP) Visual Analogue Scale (VAS) at Weeks 4, 8, 12

Secondary: Change From Baseline in the Patient’s Assessment of Arthritis Pain (PAAP) Visual Analogue Scale (VAS) at Weeks 4, 8, 12

Secondary: Change From Baseline in the Patient Global Assessment of Arthritis (PtGA) VAS at Weeks 4, 8, 12

Secondary: Change From Baseline in the Patient Global Assessment of Arthritis (PtGA) VAS at Weeks 4, 8, 12

Secondary: Change From Baseline in the Health Assessment Questionnaire – Disability Index (HAQ-DI) at Weeks 4, 8, and 12

Secondary: Change From Baseline in the Health Assessment Questionnaire – Disability Index (HAQ-DI) at Weeks 4, 8, and 12

Secondary: Change From Baseline in the 36 Item Short Form Health Survey (SF-36) Version 2 (Acute) 8 Domain Scores at Week 12

Secondary: Change From Baseline in the 36 Item Short Form Health Survey (SF-36) Version 2 (Acute) 8 Domain Scores at Week 12

Secondary: Change From Baseline in the Physical Component Score (PCS) and Mental Component Score (MCS) at Week 12

Secondary: Change From Baseline in the Physical Component Score (PCS) and Mental Component Score (MCS) at Week 12

Secondary: Change From Baseline in the European Quality of Life 5 Dimensions-3 Level (EQ-5D-3L) Score at Week 12

Secondary: Change From Baseline in the European Quality of Life 5 Dimensions-3 Level (EQ-5D-3L) Score at Week 12

Secondary: Change From Baseline in the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Total Score at Week 12

Secondary: Change From Baseline in the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Total Score at Week 12

Adverse events

Adverse events

Clinical Trial Results:
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