Trial Outcomes & Findings for A Phase 4 Trial Assessing the ImPact of Residual Inflammation Detected Via Imaging TEchniques, Drug Levels and Patient Characteristics on the Outcome of Dose TaperIng of Adalimumab in Clinical Remission Rheumatoid ArThritis (RA) Subjects (NCT NCT02198651)

Results Overview

Synovitis was assessed in three wrist regions (the distal radioulnar joint; the radiocarpal joint; the intercarpal and carpometacarpal joints) and in each Metacarpophalangeal joint (MCP) joint. The first carpometacarpal joint and the first MCP joint are not scored. The scale is 0-3. Score 0 is normal, and 1-3 (mild, moderate, severe) are by thirds of the presumed maximum volume of enhancing tissue in the synovial compartment. Flare is defined as an increase from Double-blind Baseline in DAS (Disease Activity Score) 28 erythrocyte sedimentation rate (ESR) of \> 0.6 AND DAS28 \[ESR\] \> 2.6, OR an increase in DAS28 (ESR) of ≥ 1.2 irrespective of the resulting DAS28 \[ESR\]. The association between baseline hand and wrist synovitis RAMRIS score and occurrence of rheumatoid arthritis flare up to Week 40 in the Tapering arm was examined using logistic regression, and the 95% confidence interval of the odds ratio was calculated.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

149 participants

Primary outcome timeframe

From Week 4 to Week 40

Results posted on

2019-06-25

Participant Flow

All Lead-in-Treated Subject population: participants who were enrolled in the study and received at least 1 dose of study drug during the Lead-in period. Three participants enrolled in the study but were not treated during the Lead-in period.

Participant milestones

Participant milestones
Measure	Adalimumab 40 mg Eow 40 mg adalimumab administered subcutaneously every other week (eow) from Week 0 to Week 4 (Lead-in Period)	Adalimumab Tapering 40 mg adalimumab administered subcutaneously every three weeks from Week 4 to Week 40 (Double-blind Period)	Adalimumab Withdrawal Arm Placebo administered subcutaneously every three weeks from Week 4 to Week 40 (Double-blind Period)	Adalimumab Tapering to Rescue Arm 40 mg adalimumab administered subcutaneously every other week (eow) from Flare Week 0 to Flare Week 16 (Open-Label Rescue Period)	Adalimumab Withdrawal to Rescue Arm 40 mg adalimumab administered subcutaneously every other week (eow) from Flare Week 0 to Flare Week 16 (Open-Label Rescue Period)
Lead-in Period STARTED	149	0	0	0	0
Lead-in Period Participants Treated in Lead-In Period	146	0	0	0	0
Lead-in Period COMPLETED	112	0	0	0	0
Lead-in Period NOT COMPLETED	37	0	0	0	0
Double-blind Period STARTED	0	102	20	0	0
Double-blind Period COMPLETED	0	93	19	0	0
Double-blind Period NOT COMPLETED	0	9	1	0	0
Open-label Rescue Period STARTED	0	0	0	31	8
Open-label Rescue Period Correctly Entered Open-label Rescue	0	0	0	30	8
Open-label Rescue Period COMPLETED	0	0	0	28	8
Open-label Rescue Period NOT COMPLETED	0	0	0	3	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Adalimumab 40 mg Eow 40 mg adalimumab administered subcutaneously every other week (eow) from Week 0 to Week 4 (Lead-in Period)	Adalimumab Tapering 40 mg adalimumab administered subcutaneously every three weeks from Week 4 to Week 40 (Double-blind Period)	Adalimumab Withdrawal Arm Placebo administered subcutaneously every three weeks from Week 4 to Week 40 (Double-blind Period)	Adalimumab Tapering to Rescue Arm 40 mg adalimumab administered subcutaneously every other week (eow) from Flare Week 0 to Flare Week 16 (Open-Label Rescue Period)
Lead-in Period Withdrew consent	13	0	0	0
Lead-in Period Adverse Event	2	0	0	0
Lead-in Period Other, not specified	22	0	0	0
Double-blind Period Withdrew consent	0	4	0	0
Double-blind Period Adverse Event	0	1	0	0
Double-blind Period Other, not specified	0	4	1	0
Open-label Rescue Period Withdrew consent	0	0	0	2
Open-label Rescue Period Incorrectly entered Open-label Rescue	0	0	0	1

Baseline Characteristics

Participants with available data

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Adalimumab 40 mg Eow n=146 Participants 40 mg adalimumab administered subcutaneously every other week (eow) from Week 0 to Week 4 (Lead-in Period)
Age, Continuous	59.6 years STANDARD_DEVIATION 10.30 • n=146 Participants
Sex: Female, Male Female	109 Participants n=146 Participants
Sex: Female, Male Male	37 Participants n=146 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=146 Participants
Race (NIH/OMB) Asian	2 Participants n=146 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=146 Participants
Race (NIH/OMB) Black or African American	2 Participants n=146 Participants
Race (NIH/OMB) White	139 Participants n=146 Participants
Race (NIH/OMB) More than one race	0 Participants n=146 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=146 Participants
Tobacco Use Current	22 Participants n=146 Participants
Tobacco Use Former	46 Participants n=146 Participants
Tobacco Use Never	76 Participants n=146 Participants
Tobacco Use Unknown	2 Participants n=146 Participants
Disease duration	12.9 years STANDARD_DEVIATION 9.99 • n=142 Participants • Participants with available data
Duration of adalimumab therapy	5.4 years STANDARD_DEVIATION 3.27 • n=146 Participants
Duration of remission	2.2 years STANDARD_DEVIATION 1.99 • n=125 Participants • Participants with available data
Previous treatment with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) Yes	145 Participants n=146 Participants
Previous treatment with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) No	1 Participants n=146 Participants
Previous Tx with biological disease-modifying anti-rheumatic drugs (bDMARDs; excluding adalimumab) Yes	38 Participants n=146 Participants
Previous Tx with biological disease-modifying anti-rheumatic drugs (bDMARDs; excluding adalimumab) No	108 Participants n=146 Participants
Previous Tx with csDMARDS or bDMARDs (excluding adalimumab) Yes	146 Participants n=146 Participants
Previous Tx with csDMARDS or bDMARDs (excluding adalimumab) No	0 Participants n=146 Participants
Participants' Global Assessment of Disease Activity	8.7 units on a scale STANDARD_DEVIATION 11.84 • n=146 Participants
Mean C-Reactive Protein (CRP)	2.4 mg/L STANDARD_DEVIATION 2.58 • n=146 Participants
HAQ-DI Score	0.4 units on a scale STANDARD_DEVIATION 0.51 • n=146 Participants

PRIMARY outcome

Timeframe: From Week 4 to Week 40

Population: Participants in the Tapering arm who received at least 1 dose of study drug during the Double-blind period

Synovitis was assessed in three wrist regions (the distal radioulnar joint; the radiocarpal joint; the intercarpal and carpometacarpal joints) and in each Metacarpophalangeal joint (MCP) joint. The first carpometacarpal joint and the first MCP joint are not scored. The scale is 0-3. Score 0 is normal, and 1-3 (mild, moderate, severe) are by thirds of the presumed maximum volume of enhancing tissue in the synovial compartment. Flare is defined as an increase from Double-blind Baseline in DAS (Disease Activity Score) 28 erythrocyte sedimentation rate (ESR) of \> 0.6 AND DAS28 \[ESR\] \> 2.6, OR an increase in DAS28 (ESR) of ≥ 1.2 irrespective of the resulting DAS28 \[ESR\]. The association between baseline hand and wrist synovitis RAMRIS score and occurrence of rheumatoid arthritis flare up to Week 40 in the Tapering arm was examined using logistic regression, and the 95% confidence interval of the odds ratio was calculated.

Outcome measures

Outcome measures
Measure	Non-Flared Participants Participants who did not experience flare during the Double-blind Period	Flared Participants n=102 Participants Participants who experienced flare during the Double-blind Period	CDAI ≤ 2.8 Clinical Disease Activity Index (CDAI) score ≤ 2.8
Association Between Baseline Hand and Wrist Synovitis Rheumatoid Arthritis Magnetic Resonance Imaging Scoring System (RAMRIS) Score and Flare up to Week 40 in the Tapering Arm	—	0.993 odds ratio Interval 0.822 to 1.199	—

PRIMARY outcome

Timeframe: From Week 4 to Week 40

Population: Participants in the Tapering arm who received at least 1 dose of study drug during the Double-blind period

Bone marrow edema in each bone was scored separately. The scale is 0-3 based on the proportion of bone with edema, as follows-0: no edema; 1: 1-33% of bone edematous; 2: 34-66% of bone edematous; 3: 67-100%. Flare is defined as an increase from Double-blind Baseline in DAS (Disease Activity Score) 28 erythrocyte sedimentation rate (ESR) of \> 0.6 AND DAS28 \[ESR\] \> 2.6, OR an increase in DAS28 (ESR) of ≥ 1.2 irrespective of the resulting DAS28 \[ESR\]. The association between baseline bone marrow edema rheumatoid arthritis MRI scoring system (RAMRIS) score and occurrence of rheumatoid arthritis flare up to Week 40 in the Tapering arm was examined using logistic regression, and the 95% confidence interval of the odds ratio was calculated.

Outcome measures

Outcome measures
Measure	Non-Flared Participants Participants who did not experience flare during the Double-blind Period	Flared Participants n=102 Participants Participants who experienced flare during the Double-blind Period	CDAI ≤ 2.8 Clinical Disease Activity Index (CDAI) score ≤ 2.8
Association Between Baseline Bone Marrow Edema RAMRIS Score and Flare up to Week 40 in the Tapering Arm	—	0.959 odds ratio Interval 0.821 to 1.119	—

PRIMARY outcome

Timeframe: From Week 4 to Week 40

Population: Participants in the Tapering arm who received at least 1 dose of study drug during the Double-blind period

The composite score is the sum of the baseline hand and wrist synovitis and bone marrow edema RAMRIS scores. Flare is defined as an increase from Double-blind Baseline in DAS (Disease Activity Score) 28 erythrocyte sedimentation rate (ESR) of \> 0.6 AND DAS28 \[ESR\] \> 2.6, OR an increase in DAS28 (ESR) of ≥ 1.2 irrespective of the resulting DAS28 \[ESR\]. The association between the composite baseline hand and wrist synovitis score and baseline bone marrow edema rheumatoid arthritis MRI scoring system (RAMRIS) score and occurrence of rheumatoid arthritis flare up to Week 40 in the Tapering arm was examined using logistic regression, and the 95% confidence interval of the odds ratio was calculated.

Outcome measures

Outcome measures
Measure	Non-Flared Participants Participants who did not experience flare during the Double-blind Period	Flared Participants n=102 Participants Participants who experienced flare during the Double-blind Period	CDAI ≤ 2.8 Clinical Disease Activity Index (CDAI) score ≤ 2.8
Association Between a Composite of Baseline Hand and Wrist Synovitis and Bone Marrow Edema RAMRIS Scores and Flare up to Week 40 in the Tapering Arm	—	0.979 odds ratio Interval 0.885 to 1.084	—

SECONDARY outcome

Timeframe: From Week 4 to Week 40

Population: Double-blind Treated Subject population: participants who received at least 1 dose of study drug during the Double-blind period

Time to flare was defined as the number of weeks from the date of the first dose of study drug in the Double-blind period to the date of flare.

Outcome measures

Outcome measures
Measure	Non-Flared Participants n=20 Participants Participants who did not experience flare during the Double-blind Period	Flared Participants n=102 Participants Participants who experienced flare during the Double-blind Period	CDAI ≤ 2.8 Clinical Disease Activity Index (CDAI) score ≤ 2.8
Median Time to Flare	NA weeks Interval 12.1 to NA = not estimable/calculable due to low number of events	NA weeks Interval 36.4 to NA = not estimable/calculable due to low number of events	—

SECONDARY outcome

Timeframe: At the Flare Week 0 Visit

Population: All Open-label-rescue-treated participants excluding those who falsely entered the Open-label rescue period

Physicians rated the severity of flare at the Flare Week 0 visit from 0 (not severe) to 10 (very severe). The number of participants within each level of flare severity is presented.

Outcome measures

Outcome measures
Measure	Non-Flared Participants n=8 Participants Participants who did not experience flare during the Double-blind Period	Flared Participants n=30 Participants Participants who experienced flare during the Double-blind Period	CDAI ≤ 2.8 Clinical Disease Activity Index (CDAI) score ≤ 2.8
Physicians' Assessment of Flare Severity 0	1 Participants	1 Participants	—
Physicians' Assessment of Flare Severity 1	0 Participants	2 Participants	—
Physicians' Assessment of Flare Severity 9	0 Participants	0 Participants	—
Physicians' Assessment of Flare Severity 2	0 Participants	3 Participants	—
Physicians' Assessment of Flare Severity 3	1 Participants	3 Participants	—
Physicians' Assessment of Flare Severity 4	2 Participants	6 Participants	—
Physicians' Assessment of Flare Severity 5	1 Participants	1 Participants	—
Physicians' Assessment of Flare Severity 6	0 Participants	4 Participants	—
Physicians' Assessment of Flare Severity 7	0 Participants	1 Participants	—
Physicians' Assessment of Flare Severity 8	0 Participants	0 Participants	—
Physicians' Assessment of Flare Severity 10	0 Participants	0 Participants	—
Physicians' Assessment of Flare Severity Missing	3 Participants	9 Participants	—

SECONDARY outcome

Timeframe: At the Flare Week 0 Visit

Population: All Open-label-rescue-treated participants excluding those who falsely entered the Open-label rescue period

Participants rated the severity of flare at the Flare Week 0 visit from 0 (not severe) to 10 (very severe). The number of participants within each level of flare severity is presented.

Outcome measures

Outcome measures
Measure	Non-Flared Participants n=8 Participants Participants who did not experience flare during the Double-blind Period	Flared Participants n=30 Participants Participants who experienced flare during the Double-blind Period	CDAI ≤ 2.8 Clinical Disease Activity Index (CDAI) score ≤ 2.8
Participants' Assessment of Flare Severity Missing	3 Participants	8 Participants	—
Participants' Assessment of Flare Severity 0	0 Participants	1 Participants	—
Participants' Assessment of Flare Severity 1	1 Participants	2 Participants	—
Participants' Assessment of Flare Severity 2	2 Participants	2 Participants	—
Participants' Assessment of Flare Severity 3	0 Participants	3 Participants	—
Participants' Assessment of Flare Severity 4	0 Participants	4 Participants	—
Participants' Assessment of Flare Severity 5	1 Participants	1 Participants	—
Participants' Assessment of Flare Severity 6	1 Participants	4 Participants	—
Participants' Assessment of Flare Severity 7	0 Participants	1 Participants	—
Participants' Assessment of Flare Severity 8	0 Participants	2 Participants	—
Participants' Assessment of Flare Severity 9	0 Participants	0 Participants	—
Participants' Assessment of Flare Severity 10	0 Participants	2 Participants	—

SECONDARY outcome

Timeframe: From Week 4 to Week 40

Population: Double-blind Treated Subject population: participants who received at least 1 dose of study drug during the Double-blind period

Flare was defined as an increase from Double-blind Baseline in DAS (Disease Activity Score) 28 erythrocyte sedimentation rate (ESR) of \> 0.6 AND DAS28 \[ESR\] \> 2.6, OR an increase in DAS28 (ESR) of ≥ 1.2 irrespective of the resulting DAS28 \[ESR\].

Outcome measures

Outcome measures
Measure	Non-Flared Participants n=20 Participants Participants who did not experience flare during the Double-blind Period	Flared Participants n=102 Participants Participants who experienced flare during the Double-blind Period	CDAI ≤ 2.8 Clinical Disease Activity Index (CDAI) score ≤ 2.8
Percentage of Participants With a Flare	45.0 percentage of participants Interval 23.1 to 68.5	36.3 percentage of participants Interval 27.0 to 46.4	—

SECONDARY outcome

Timeframe: From Flare Week 0 to Flare Week 16

Population: All Open-label rescue-treated participants excluding those who incorrectly entered the Open-label Rescue Period; last observation carried forward

The Disease Activity Score 28 (DAS28) is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, the erythrocyte sedimentation rate (ESR; mm/hour), and the participant's assessment of global disease activity (on a visual analog scale \[VAS\] from 0 to 10 cm) are included in the DAS28 (ESR) score. Scores on the DAS28 range from 0 to 10; higher scores indicate more disease activity. Clinical remission was defined as DAS28 (ESR) \< 2.6.

Outcome measures

Outcome measures
Measure	Non-Flared Participants n=8 Participants Participants who did not experience flare during the Double-blind Period	Flared Participants n=30 Participants Participants who experienced flare during the Double-blind Period	CDAI ≤ 2.8 Clinical Disease Activity Index (CDAI) score ≤ 2.8
Number of Participants Who Regained Clinical Remission in the Open-Label Rescue Arm Over Time Flare Week 16	4 Participants	13 Participants	—
Number of Participants Who Regained Clinical Remission in the Open-Label Rescue Arm Over Time Flare Week 0	1 Participants	3 Participants	—
Number of Participants Who Regained Clinical Remission in the Open-Label Rescue Arm Over Time Flare Week 4	1 Participants	14 Participants	—
Number of Participants Who Regained Clinical Remission in the Open-Label Rescue Arm Over Time Flare Week 10	3 Participants	17 Participants	—

SECONDARY outcome

Timeframe: From Flare Week 0 to Flare Week 16

Population: All Open-label rescue treated participants excluding those who incorrectly entered the Open-label Rescue Period

The Disease Activity Score 28 (DAS28) is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, the erythrocyte sedimentation rate (ESR; mm/hour), and the participant's assessment of global disease activity (on a visual analog scale \[VAS\] from 0 to 10 cm) are included in the DAS28 (ESR) score. Scores on the DAS28 range from 0 to 10; higher scores indicate more disease activity. Clinical remission was defined as DAS28 (ESR) \< 2.6. Time to clinical remission was defined as the number of weeks from the occurrence of flare to the first date of clinical remission.

Outcome measures

Outcome measures
Measure	Non-Flared Participants n=8 Participants Participants who did not experience flare during the Double-blind Period	Flared Participants n=30 Participants Participants who experienced flare during the Double-blind Period	CDAI ≤ 2.8 Clinical Disease Activity Index (CDAI) score ≤ 2.8
Median Time to Clinical Remission From the Occurrence of Flare	18.0 weeks Interval 0.1 to 18.0	6.1 weeks Interval 4.1 to 16.3	—

SECONDARY outcome

Timeframe: From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16

Population: Double-blind Treated Subject population: participants who received at least 1 dose of study drug during the Double-blind period and had at least Double-blind Baseline data for this endpoint

The Disease Activity Score 28 (DAS28) is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, the erythrocyte sedimentation rate (ESR; mm/hour), and the participant's assessment of global disease activity (on a visual analog scale \[VAS\] from 0 to 10 cm) are included in the DAS28 (ESR) score. Scores on the DAS28 range from 0 to 10; higher scores indicate more disease activity. Negative values indicate improvement from baseline.

Outcome measures

Outcome measures
Measure	Non-Flared Participants n=76 Participants Participants who did not experience flare during the Double-blind Period	Flared Participants n=46 Participants Participants who experienced flare during the Double-blind Period	CDAI ≤ 2.8 Clinical Disease Activity Index (CDAI) score ≤ 2.8
Mean Change From Double-blind Baseline in Disease Activity Score 28 (DAS28) Flare Week 16- Withdrawal Arm	—	0.6 units on a scale Standard Deviation 0.80	—
Mean Change From Double-blind Baseline in Disease Activity Score 28 (DAS28) Flare Week 4- Withdrawal Arm	—	1.2 units on a scale Standard Deviation 1.14	—
Mean Change From Double-blind Baseline in Disease Activity Score 28 (DAS28) Flare Week 0- Withdrawal Arm	—	1.9 units on a scale Standard Deviation 0.96	—
Mean Change From Double-blind Baseline in Disease Activity Score 28 (DAS28) Flare Week 4- Tapering Arm	—	1.3 units on a scale Standard Deviation 1.05	—
Mean Change From Double-blind Baseline in Disease Activity Score 28 (DAS28) Flare Week 10- Tapering Arm	—	0.9 units on a scale Standard Deviation 0.81	—
Mean Change From Double-blind Baseline in Disease Activity Score 28 (DAS28) Flare Week 10- Withdrawal Arm	—	0.7 units on a scale Standard Deviation 0.50	—
Mean Change From Double-blind Baseline in Disease Activity Score 28 (DAS28) Flare Week 16- Tapering Arm	—	1.2 units on a scale Standard Deviation 1.04	—
Mean Change From Double-blind Baseline in Disease Activity Score 28 (DAS28) Double Blind Week 10- Tapering Arm	0.1 units on a scale Standard Deviation 0.46	0.7 units on a scale Standard Deviation 1.27	—
Mean Change From Double-blind Baseline in Disease Activity Score 28 (DAS28) Double Blind Week 10- Withdrawal Arm	0.1 units on a scale Standard Deviation 0.55	0.1 units on a scale Standard Deviation 0.47	—
Mean Change From Double-blind Baseline in Disease Activity Score 28 (DAS28) Double Blind Week 16- Tapering Arm	0.1 units on a scale Standard Deviation 0.39	1.2 units on a scale Standard Deviation 1.34	—
Mean Change From Double-blind Baseline in Disease Activity Score 28 (DAS28) Double Blind Week 16- Withdrawal Arm	0.0 units on a scale Standard Deviation 0.43	0.9 units on a scale Standard Deviation 0.58	—
Mean Change From Double-blind Baseline in Disease Activity Score 28 (DAS28) Double Blind Week 22- Tapering Arm	-0.0 units on a scale Standard Deviation 0.53	0.7 units on a scale Standard Deviation 1.18	—
Mean Change From Double-blind Baseline in Disease Activity Score 28 (DAS28) Double Blind Week 22- Withdrawal Arm	0.1 units on a scale Standard Deviation 0.24	0.5 units on a scale Standard Deviation 0.31	—
Mean Change From Double-blind Baseline in Disease Activity Score 28 (DAS28) Double Blind Week 28- Tapering arm	0.1 units on a scale Standard Deviation 0.50	0.8 units on a scale Standard Deviation 1.16	—
Mean Change From Double-blind Baseline in Disease Activity Score 28 (DAS28) Double Blind Week 28- Withdrawal arm	0.2 units on a scale Standard Deviation 0.25	1.0 units on a scale Standard Deviation 1.54	—
Mean Change From Double-blind Baseline in Disease Activity Score 28 (DAS28) Double Blind Week 34- Tapering Arm	-0.0 units on a scale Standard Deviation 0.54	0.7 units on a scale Standard Deviation 0.59	—
Mean Change From Double-blind Baseline in Disease Activity Score 28 (DAS28) Double Blind Week 34- Withdrawal Arm	-0.0 units on a scale Standard Deviation 0.46	-0.7 units on a scale Standard Deviation 0.11	—
Mean Change From Double-blind Baseline in Disease Activity Score 28 (DAS28) Double Blind Week 40- Tapering Arm	0.0 units on a scale Standard Deviation 0.52	1.5 units on a scale Standard Deviation 1.20	—
Mean Change From Double-blind Baseline in Disease Activity Score 28 (DAS28) Double Blind Week 40- Withdrawal Arm	0.2 units on a scale Standard Deviation 0.38	0.8 units on a scale Standard Deviation 2.18	—
Mean Change From Double-blind Baseline in Disease Activity Score 28 (DAS28) Flare Week 0- Tapering Arm	—	2.3 units on a scale Standard Deviation 1.15	—

SECONDARY outcome

Timeframe: From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16

Population: Double-blind Treated Subject population: participants who received at least 1 dose of study drug during the Double-blind period and had at least Double-blind Baseline data for this endpoint

The CDAI is a validated measure of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, global health assessed by the participant on a visual analogue scale from 0 to 10 (cm), and global health assessed by an investigator on a visual analogue scale from 0 to 10 (cm) were included in the CDAI score. Scores on the CDAI range from 0 to 76; higher scores indicate more disease activity. Negative values indicate improvement from the Double-blind baseline score.

Outcome measures

Outcome measures
Measure	Non-Flared Participants n=76 Participants Participants who did not experience flare during the Double-blind Period	Flared Participants n=46 Participants Participants who experienced flare during the Double-blind Period	CDAI ≤ 2.8 Clinical Disease Activity Index (CDAI) score ≤ 2.8
Mean Change From Double-blind Baseline in Clinical Disease Activity Index (CDAI) Score Double Blind Week 10- Tapering Arm	0.6 units on a scale Standard Deviation 1.34	4.4 units on a scale Standard Deviation 7.68	—
Mean Change From Double-blind Baseline in Clinical Disease Activity Index (CDAI) Score Double Blind Week 10- Withdrawal Arm	1.4 units on a scale Standard Deviation 2.85	1.0 units on a scale Standard Deviation 2.45	—
Mean Change From Double-blind Baseline in Clinical Disease Activity Index (CDAI) Score Double Blind Week 16- Tapering Arm	0.4 units on a scale Standard Deviation 1.30	7.0 units on a scale Standard Deviation 9.35	—
Mean Change From Double-blind Baseline in Clinical Disease Activity Index (CDAI) Score Double Blind Week 16- Withdrawal Arm	-0.1 units on a scale Standard Deviation 0.88	2.9 units on a scale Standard Deviation 2.42	—
Mean Change From Double-blind Baseline in Clinical Disease Activity Index (CDAI) Score Double Blind Week 22- Tapering Arm	0.3 units on a scale Standard Deviation 1.38	3.2 units on a scale Standard Deviation 4.98	—
Mean Change From Double-blind Baseline in Clinical Disease Activity Index (CDAI) Score Double Blind Week 22- Withdrawal Arm	0.1 units on a scale Standard Deviation 0.73	2.2 units on a scale Standard Deviation 1.93	—
Mean Change From Double-blind Baseline in Clinical Disease Activity Index (CDAI) Score Double Blind Week 28- Tapering arm	0.5 units on a scale Standard Deviation 1.37	3.7 units on a scale Standard Deviation 6.19	—
Mean Change From Double-blind Baseline in Clinical Disease Activity Index (CDAI) Score Double Blind Week 28- Withdrawal arm	-0.1 units on a scale Standard Deviation 0.80	6.3 units on a scale Standard Deviation 8.40	—
Mean Change From Double-blind Baseline in Clinical Disease Activity Index (CDAI) Score Double Blind Week 34- Tapering Arm	0.2 units on a scale Standard Deviation 1.08	2.7 units on a scale Standard Deviation 3.04	—
Mean Change From Double-blind Baseline in Clinical Disease Activity Index (CDAI) Score Double Blind Week 34- Withdrawal Arm	0.0 units on a scale Standard Deviation 0.92	-0.1 units on a scale Standard Deviation 0.14	—
Mean Change From Double-blind Baseline in Clinical Disease Activity Index (CDAI) Score Double Blind Week 40- Tapering Arm	0.1 units on a scale Standard Deviation 1.33	7.4 units on a scale Standard Deviation 10.04	—
Mean Change From Double-blind Baseline in Clinical Disease Activity Index (CDAI) Score Double Blind Week 40- Withdrawal Arm	-0.3 units on a scale Standard Deviation 0.48	7.7 units on a scale Standard Deviation 11.38	—
Mean Change From Double-blind Baseline in Clinical Disease Activity Index (CDAI) Score Flare Week 0- Tapering Arm	—	12.3 units on a scale Standard Deviation 9.56	—
Mean Change From Double-blind Baseline in Clinical Disease Activity Index (CDAI) Score Flare Week 0- Withdrawal Arm	—	9.4 units on a scale Standard Deviation 9.13	—
Mean Change From Double-blind Baseline in Clinical Disease Activity Index (CDAI) Score Flare Week 4- Tapering Arm	—	5.0 units on a scale Standard Deviation 6.55	—
Mean Change From Double-blind Baseline in Clinical Disease Activity Index (CDAI) Score Flare Week 4- Withdrawal Arm	—	5.4 units on a scale Standard Deviation 9.59	—
Mean Change From Double-blind Baseline in Clinical Disease Activity Index (CDAI) Score Flare Week 10- Tapering Arm	—	3.5 units on a scale Standard Deviation 4.55	—
Mean Change From Double-blind Baseline in Clinical Disease Activity Index (CDAI) Score Flare Week 10- Withdrawal Arm	—	3.6 units on a scale Standard Deviation 2.52	—
Mean Change From Double-blind Baseline in Clinical Disease Activity Index (CDAI) Score Flare Week 16- Tapering Arm	—	4.5 units on a scale Standard Deviation 6.14	—
Mean Change From Double-blind Baseline in Clinical Disease Activity Index (CDAI) Score Flare Week 16- Withdrawal Arm	—	2.8 units on a scale Standard Deviation 4.19	—

SECONDARY outcome

Timeframe: From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16

Population: Double-blind Treated Subject population: participants who received at least 1 dose of study drug during the Double-blind period and had at least Double-blind Baseline data for this endpoint

The SDAI is a validated measure of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, global health assessed by the participant on a visual analogue scale from 0 to 10 (cm), global health assessed by an investigator on a visual analogue scale from 0 to 10 (cm), and serum levels of C-reactive protein levels (mg/dL) were included in the SDAI score. Scores on the SDAI range from 0 to 86; higher scores indicate more disease activity. Negative values indicate improvement from the Double-blind baseline score.

Outcome measures

Outcome measures
Measure	Non-Flared Participants n=76 Participants Participants who did not experience flare during the Double-blind Period	Flared Participants n=46 Participants Participants who experienced flare during the Double-blind Period	CDAI ≤ 2.8 Clinical Disease Activity Index (CDAI) score ≤ 2.8
Mean Change From Double-blind Baseline in Simplified Disease Activity Index (SDAI) Score Double Blind Week 16- Tapering Arm	0.4 units on a scale Standard Deviation 1.35	6.3 units on a scale Standard Deviation 10.25	—
Mean Change From Double-blind Baseline in Simplified Disease Activity Index (SDAI) Score Double Blind Week 10- Tapering Arm	0.8 units on a scale Standard Deviation 1.85	3.7 units on a scale Standard Deviation 8.57	—
Mean Change From Double-blind Baseline in Simplified Disease Activity Index (SDAI) Score Double Blind Week 10- Withdrawal Arm	1.3 units on a scale Standard Deviation 2.67	0.9 units on a scale Standard Deviation 2.59	—
Mean Change From Double-blind Baseline in Simplified Disease Activity Index (SDAI) Score Double Blind Week 16- Withdrawal Arm	-0.1 units on a scale Standard Deviation 0.90	3.6 units on a scale Standard Deviation 2.80	—
Mean Change From Double-blind Baseline in Simplified Disease Activity Index (SDAI) Score Double Blind Week 22- Tapering Arm	0.3 units on a scale Standard Deviation 1.47	3.6 units on a scale Standard Deviation 5.18	—
Mean Change From Double-blind Baseline in Simplified Disease Activity Index (SDAI) Score Double Blind Week 22- Withdrawal Arm	-0.0 units on a scale Standard Deviation 0.88	2.3 units on a scale Standard Deviation 1.95	—
Mean Change From Double-blind Baseline in Simplified Disease Activity Index (SDAI) Score Double Blind Week 28- Tapering arm	0.4 units on a scale Standard Deviation 1.37	3.8 units on a scale Standard Deviation 6.34	—
Mean Change From Double-blind Baseline in Simplified Disease Activity Index (SDAI) Score Double Blind Week 28- Withdrawal arm	0.1 units on a scale Standard Deviation 1.61	6.4 units on a scale Standard Deviation 8.40	—
Mean Change From Double-blind Baseline in Simplified Disease Activity Index (SDAI) Score Double Blind Week 34- Tapering Arm	0.2 units on a scale Standard Deviation 1.17	3.0 units on a scale Standard Deviation 3.29	—
Mean Change From Double-blind Baseline in Simplified Disease Activity Index (SDAI) Score Double Blind Week 34- Withdrawal Arm	0.1 units on a scale Standard Deviation 1.07	0.1 units on a scale Standard Deviation 0.33	—
Mean Change From Double-blind Baseline in Simplified Disease Activity Index (SDAI) Score Double Blind Week 40- Tapering Arm	0.1 units on a scale Standard Deviation 1.37	7.5 units on a scale Standard Deviation 10.27	—
Mean Change From Double-blind Baseline in Simplified Disease Activity Index (SDAI) Score Double Blind Week 40- Withdrawal Arm	-0.3 units on a scale Standard Deviation 0.62	8.5 units on a scale Standard Deviation 10.23	—
Mean Change From Double-blind Baseline in Simplified Disease Activity Index (SDAI) Score Flare Week 0- Tapering Arm	—	11.6 units on a scale Standard Deviation 11.17	—
Mean Change From Double-blind Baseline in Simplified Disease Activity Index (SDAI) Score Flare Week 0- Withdrawal Arm	—	9.9 units on a scale Standard Deviation 8.31	—
Mean Change From Double-blind Baseline in Simplified Disease Activity Index (SDAI) Score Flare Week 4- Tapering Arm	—	4.1 units on a scale Standard Deviation 8.73	—
Mean Change From Double-blind Baseline in Simplified Disease Activity Index (SDAI) Score Flare Week 4- Withdrawal Arm	—	5.2 units on a scale Standard Deviation 9.64	—
Mean Change From Double-blind Baseline in Simplified Disease Activity Index (SDAI) Score Flare Week 10- Tapering Arm	—	2.5 units on a scale Standard Deviation 7.53	—
Mean Change From Double-blind Baseline in Simplified Disease Activity Index (SDAI) Score Flare Week 10- Withdrawal Arm	—	3.5 units on a scale Standard Deviation 2.51	—
Mean Change From Double-blind Baseline in Simplified Disease Activity Index (SDAI) Score Flare Week 16- Tapering Arm	—	3.6 units on a scale Standard Deviation 6.63	—
Mean Change From Double-blind Baseline in Simplified Disease Activity Index (SDAI) Score Flare Week 16- Withdrawal Arm	—	2.7 units on a scale Standard Deviation 4.20	—

SECONDARY outcome

Timeframe: From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16

Population: Double-blind Treated Subject population: participants who received at least 1 dose of study drug during the Double-blind period; last observation carried forward

The maintenance of clinical remission after regaining remission during the Open-label rescue period was defined as either Disease Activity Score 28 (DAS28 ESR) \< 2.6, Simplified Disease Activity Index (SDAI) score ≤ 3.3, or Clinical Disease Activity Index (CDAI) score ≤ 2.8).

Outcome measures

Outcome measures
Measure	Non-Flared Participants n=122 Participants Participants who did not experience flare during the Double-blind Period	Flared Participants n=122 Participants Participants who experienced flare during the Double-blind Period	CDAI ≤ 2.8 n=122 Participants Clinical Disease Activity Index (CDAI) score ≤ 2.8
Number of Participants Maintaining Clinical Remission Defined By DAS28 (ESR) < 2.6, SDAI ≤ 3.3, and CDAI ≤ 2.8 at Each Visit By Treatment Arm Double Blind Baseline- Tapering Arm	89 Participants	102 Participants	85 Participants
Number of Participants Maintaining Clinical Remission Defined By DAS28 (ESR) < 2.6, SDAI ≤ 3.3, and CDAI ≤ 2.8 at Each Visit By Treatment Arm Double Blind Baseline- Withdrawal Arm	19 Participants	20 Participants	19 Participants
Number of Participants Maintaining Clinical Remission Defined By DAS28 (ESR) < 2.6, SDAI ≤ 3.3, and CDAI ≤ 2.8 at Each Visit By Treatment Arm Double Blind Week 10- Tapering Arm	63 Participants	85 Participants	62 Participants
Number of Participants Maintaining Clinical Remission Defined By DAS28 (ESR) < 2.6, SDAI ≤ 3.3, and CDAI ≤ 2.8 at Each Visit By Treatment Arm Double Blind Week 10- Withdrawal Arm	16 Participants	18 Participants	14 Participants
Number of Participants Maintaining Clinical Remission Defined By DAS28 (ESR) < 2.6, SDAI ≤ 3.3, and CDAI ≤ 2.8 at Each Visit By Treatment Arm Double Blind Week 16- Tapering Arm	64 Participants	78 Participants	62 Participants
Number of Participants Maintaining Clinical Remission Defined By DAS28 (ESR) < 2.6, SDAI ≤ 3.3, and CDAI ≤ 2.8 at Each Visit By Treatment Arm Double Blind Week 16- Withdrawal arm	13 Participants	15 Participants	15 Participants
Number of Participants Maintaining Clinical Remission Defined By DAS28 (ESR) < 2.6, SDAI ≤ 3.3, and CDAI ≤ 2.8 at Each Visit By Treatment Arm Double Blind Week 22- Tapering Arm	59 Participants	75 Participants	58 Participants
Number of Participants Maintaining Clinical Remission Defined By DAS28 (ESR) < 2.6, SDAI ≤ 3.3, and CDAI ≤ 2.8 at Each Visit By Treatment Arm Double Blind Week 22- Withdrawal Arm	13 Participants	14 Participants	13 Participants
Number of Participants Maintaining Clinical Remission Defined By DAS28 (ESR) < 2.6, SDAI ≤ 3.3, and CDAI ≤ 2.8 at Each Visit By Treatment Arm Double Blind Week 28- Tapering Arm	58 Participants	69 Participants	57 Participants
Number of Participants Maintaining Clinical Remission Defined By DAS28 (ESR) < 2.6, SDAI ≤ 3.3, and CDAI ≤ 2.8 at Each Visit By Treatment Arm Double Blind Week 28- Withdrawal Arm	12 Participants	13 Participants	13 Participants
Number of Participants Maintaining Clinical Remission Defined By DAS28 (ESR) < 2.6, SDAI ≤ 3.3, and CDAI ≤ 2.8 at Each Visit By Treatment Arm Double Blind Week 34- Tapering Arm	58 Participants	70 Participants	58 Participants
Number of Participants Maintaining Clinical Remission Defined By DAS28 (ESR) < 2.6, SDAI ≤ 3.3, and CDAI ≤ 2.8 at Each Visit By Treatment Arm Double Blind Week 34- Withdrawal Arm	13 Participants	13 Participants	13 Participants
Number of Participants Maintaining Clinical Remission Defined By DAS28 (ESR) < 2.6, SDAI ≤ 3.3, and CDAI ≤ 2.8 at Each Visit By Treatment Arm Double Blind Week 40- Tapering Arm	57 Participants	64 Participants	56 Participants
Number of Participants Maintaining Clinical Remission Defined By DAS28 (ESR) < 2.6, SDAI ≤ 3.3, and CDAI ≤ 2.8 at Each Visit By Treatment Arm Double Blind Week 40- Withdrawal Arm	12 Participants	11 Participants	12 Participants
Number of Participants Maintaining Clinical Remission Defined By DAS28 (ESR) < 2.6, SDAI ≤ 3.3, and CDAI ≤ 2.8 at Each Visit By Treatment Arm Flare Week 0- Tapering Arm	4 Participants	4 Participants	4 Participants
Number of Participants Maintaining Clinical Remission Defined By DAS28 (ESR) < 2.6, SDAI ≤ 3.3, and CDAI ≤ 2.8 at Each Visit By Treatment Arm Flare Week 0- Withdrawal Arm	0 Participants	1 Participants	2 Participants
Number of Participants Maintaining Clinical Remission Defined By DAS28 (ESR) < 2.6, SDAI ≤ 3.3, and CDAI ≤ 2.8 at Each Visit By Treatment Arm Flare Week 4- Tapering Arm	13 Participants	14 Participants	13 Participants
Number of Participants Maintaining Clinical Remission Defined By DAS28 (ESR) < 2.6, SDAI ≤ 3.3, and CDAI ≤ 2.8 at Each Visit By Treatment Arm Flare Week 4- Withdrawal Arm	2 Participants	1 Participants	2 Participants
Number of Participants Maintaining Clinical Remission Defined By DAS28 (ESR) < 2.6, SDAI ≤ 3.3, and CDAI ≤ 2.8 at Each Visit By Treatment Arm Flare Week 10- Tapering Arm	14 Participants	17 Participants	14 Participants
Number of Participants Maintaining Clinical Remission Defined By DAS28 (ESR) < 2.6, SDAI ≤ 3.3, and CDAI ≤ 2.8 at Each Visit By Treatment Arm Flare Week 10- Withdrawal Arm	2 Participants	3 Participants	2 Participants
Number of Participants Maintaining Clinical Remission Defined By DAS28 (ESR) < 2.6, SDAI ≤ 3.3, and CDAI ≤ 2.8 at Each Visit By Treatment Arm Flare Week 16- Tapering Arm	13 Participants	13 Participants	13 Participants
Number of Participants Maintaining Clinical Remission Defined By DAS28 (ESR) < 2.6, SDAI ≤ 3.3, and CDAI ≤ 2.8 at Each Visit By Treatment Arm Flare Week 16- Withdrawal Arm	4 Participants	4 Participants	4 Participants

SECONDARY outcome

Timeframe: From Week 4 to Week 40 or Final visit

Population: Double-blind Treated Subject population: participants who received at least 1 dose of study drug during the Double-blind period and had at least Double-blind Baseline data for this endpoint

Synovitis was assessed in three wrist regions (the distal radioulnar joint; the radiocarpal joint; the intercarpal and carpometacarpal joints) and in each Metacarpophalangeal joint (MCP) joint. The first carpometacarpal joint and the first MCP joint are not scored. The scale is 0-3. Score 0 is normal, and 1-3 (mild, moderate, severe) are by thirds of the presumed maximum volume of enhancing tissue in the synovial compartment.

Outcome measures

Outcome measures
Measure	Non-Flared Participants n=76 Participants Participants who did not experience flare during the Double-blind Period	Flared Participants n=45 Participants Participants who experienced flare during the Double-blind Period	CDAI ≤ 2.8 Clinical Disease Activity Index (CDAI) score ≤ 2.8
Mean Change From Double-blind Baseline to Week 40 or Final Visit in Magnetic Resonance Imaging (MRI) Synovitis Score Double Blind Week 40- Tapering Arm	0.1 units on a scale Standard Deviation 1.33	-0.1 units on a scale Standard Deviation 1.20	—
Mean Change From Double-blind Baseline to Week 40 or Final Visit in Magnetic Resonance Imaging (MRI) Synovitis Score Double Blind Week 40- Withdrawal Arm	-0.1 units on a scale Standard Deviation 0.90	0.0 units on a scale	—
Mean Change From Double-blind Baseline to Week 40 or Final Visit in Magnetic Resonance Imaging (MRI) Synovitis Score Flare Week 16- Tapering Arm	—	0.8 units on a scale Standard Deviation 1.84	—
Mean Change From Double-blind Baseline to Week 40 or Final Visit in Magnetic Resonance Imaging (MRI) Synovitis Score Flare Week 16- Withdrawal Arm	—	0.1 units on a scale Standard Deviation 1.81	—

SECONDARY outcome

Timeframe: From Week 4 to Week 40 or Final visit

Population: Double-blind Treated Subject population: participants who received at least 1 dose of study drug during the Double-blind period and had at least Double-blind Baseline data for this endpoint

Bone edema in each bone was scored separately. The scale is 0-3 based on the proportion of bone with edema, as follows-0: no edema; 1: 1-33% of bone edematous; 2: 34-66% of bone edematous; 3: 67-100%.

Outcome measures

Outcome measures
Measure	Non-Flared Participants n=76 Participants Participants who did not experience flare during the Double-blind Period	Flared Participants n=46 Participants Participants who experienced flare during the Double-blind Period	CDAI ≤ 2.8 Clinical Disease Activity Index (CDAI) score ≤ 2.8
Mean Change From Double-blind Baseline to Week 40 or Final Visit in Bone Marrow Edema (BME) Score Double Blind Week 40- Tapering Arm	0.0 units on a scale Standard Deviation 1.07	-0.5 units on a scale Standard Deviation 0.84	—
Mean Change From Double-blind Baseline to Week 40 or Final Visit in Bone Marrow Edema (BME) Score Double Blind Week 40- Withdrawal Arm	1.2 units on a scale Standard Deviation 3.52	0.0 units on a scale	—
Mean Change From Double-blind Baseline to Week 40 or Final Visit in Bone Marrow Edema (BME) Score Flare Week 16- Tapering Arm	—	-0.1 units on a scale Standard Deviation 0.47	—
Mean Change From Double-blind Baseline to Week 40 or Final Visit in Bone Marrow Edema (BME) Score Flare Week 16- Withdrawal Arm	—	0.3 units on a scale Standard Deviation 0.38	—

SECONDARY outcome

Timeframe: From Week 4 to Week 40 or Final Visit

Population: Double-blind Treated Subject population: participants who received at least 1 dose of study drug during the Double-blind period and had at least Double-blind Baseline data for this endpoint

Bone erosions in each bone (wrists: carpal bones, distal radius, distal ulna, metacarpal bases; MCP joints: metacarpal heads, phalangeal bases) were scored separately. The scale is 0-10, based on the proportion of eroded bone compared to the ''assessed bone volume'', judged on all available images-0: no erosion; 1: 1-10% of bone eroded; 2; 11-20%, etc.

Outcome measures

Outcome measures
Measure	Non-Flared Participants n=76 Participants Participants who did not experience flare during the Double-blind Period	Flared Participants n=46 Participants Participants who experienced flare during the Double-blind Period	CDAI ≤ 2.8 Clinical Disease Activity Index (CDAI) score ≤ 2.8
Mean Change From Double-blind Baseline to Week 40 or Final Visit in Bone Erosions Rheumatoid Arthritis Magnetic Resonance Imaging Scoring System (RAMRIS) Score Double Blind Week 40- Tapering Arm	0.1 units on a scale Standard Deviation 0.52	-0.5 units on a scale Standard Deviation 1.73	—
Mean Change From Double-blind Baseline to Week 40 or Final Visit in Bone Erosions Rheumatoid Arthritis Magnetic Resonance Imaging Scoring System (RAMRIS) Score Double Blind Week 40- Withdrawal Arm	0.0 units on a scale Standard Deviation 1.08	-2.0 units on a scale	—
Mean Change From Double-blind Baseline to Week 40 or Final Visit in Bone Erosions Rheumatoid Arthritis Magnetic Resonance Imaging Scoring System (RAMRIS) Score Flare Week 16- Tapering Arm	—	0.3 units on a scale Standard Deviation 1.02	—
Mean Change From Double-blind Baseline to Week 40 or Final Visit in Bone Erosions Rheumatoid Arthritis Magnetic Resonance Imaging Scoring System (RAMRIS) Score Flare Week 16- Withdrawal Arm	—	0.1 units on a scale Standard Deviation 0.88	—

SECONDARY outcome

Timeframe: From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16

Population: Double-blind Treated Subject population: participants who received at least 1 dose of study drug during the Double-blind period and had at least Double-blind Baseline data for this endpoint

The Health Assessment Questionnaire - Disability Index (HAQ-DI) is a participant-reported questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task were summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. The minimal clinically important difference (MCID) defined for the HAQ-DI is ≥ 0.22.

Outcome measures

Outcome measures
Measure	Non-Flared Participants n=76 Participants Participants who did not experience flare during the Double-blind Period	Flared Participants n=46 Participants Participants who experienced flare during the Double-blind Period	CDAI ≤ 2.8 Clinical Disease Activity Index (CDAI) score ≤ 2.8
Mean Change From Double-blind Baseline in Health Assessment Questionnaire- Disability Index (HAQ-DI) Score Over Time Double Blind Week 10- Tapering Arm	0.0 units on a scale Standard Deviation 0.18	0.1 units on a scale Standard Deviation 0.3	—
Mean Change From Double-blind Baseline in Health Assessment Questionnaire- Disability Index (HAQ-DI) Score Over Time Double Blind Week 10- Withdrawal Arm	0.0 units on a scale Standard Deviation 0.17	0.3 units on a scale Standard Deviation 0.61	—
Mean Change From Double-blind Baseline in Health Assessment Questionnaire- Disability Index (HAQ-DI) Score Over Time Double Blind Week 16- Tapering Arm	-0.0 units on a scale Standard Deviation 0.28	0.2 units on a scale Standard Deviation 0.40	—
Mean Change From Double-blind Baseline in Health Assessment Questionnaire- Disability Index (HAQ-DI) Score Over Time Double Blind Week 16- Withdrawal Arm	-0.0 units on a scale Standard Deviation 0.12	0.3 units on a scale Standard Deviation 0.54	—
Mean Change From Double-blind Baseline in Health Assessment Questionnaire- Disability Index (HAQ-DI) Score Over Time Double Blind Week 22- Tapering Arm	-0.0 units on a scale Standard Deviation 0.26	0.1 units on a scale Standard Deviation 0.37	—
Mean Change From Double-blind Baseline in Health Assessment Questionnaire- Disability Index (HAQ-DI) Score Over Time Double Blind Week 22- Withdrawal Arm	0.1 units on a scale Standard Deviation 0.39	0.4 units on a scale Standard Deviation 0.79	—
Mean Change From Double-blind Baseline in Health Assessment Questionnaire- Disability Index (HAQ-DI) Score Over Time Double Blind Week 28- Tapering Arm	-0.0 units on a scale Standard Deviation 0.27	0.2 units on a scale Standard Deviation 0.43	—
Mean Change From Double-blind Baseline in Health Assessment Questionnaire- Disability Index (HAQ-DI) Score Over Time Double Blind Week 28- Withdrawal Arm	-0.1 units on a scale Standard Deviation 0.15	0.7 units on a scale Standard Deviation 0.69	—
Mean Change From Double-blind Baseline in Health Assessment Questionnaire- Disability Index (HAQ-DI) Score Over Time Double Blind Week 34- Tapering Arm	-0.0 units on a scale Standard Deviation 0.30	0.3 units on a scale Standard Deviation 0.49	—
Mean Change From Double-blind Baseline in Health Assessment Questionnaire- Disability Index (HAQ-DI) Score Over Time Double Blind Week 34- Withdrawal Arm	0.1 units on a scale Standard Deviation 0.17	0.2 units on a scale Standard Deviation 0.27	—
Mean Change From Double-blind Baseline in Health Assessment Questionnaire- Disability Index (HAQ-DI) Score Over Time Double Blind Week 40- Tapering Arm	-0.1 units on a scale Standard Deviation 0.33	0.4 units on a scale Standard Deviation 0.40	—
Mean Change From Double-blind Baseline in Health Assessment Questionnaire- Disability Index (HAQ-DI) Score Over Time Double Blind Week 40- Withdrawal Arm	0.0 units on a scale Standard Deviation 0.16	1.9 units on a scale	—
Mean Change From Double-blind Baseline in Health Assessment Questionnaire- Disability Index (HAQ-DI) Score Over Time Flare Week 0- Tapering Arm	—	0.4 units on a scale Standard Deviation 0.57	—
Mean Change From Double-blind Baseline in Health Assessment Questionnaire- Disability Index (HAQ-DI) Score Over Time Flare Week 0- Withdrawal Arm	—	0.3 units on a scale Standard Deviation 0.29	—
Mean Change From Double-blind Baseline in Health Assessment Questionnaire- Disability Index (HAQ-DI) Score Over Time Flare Week 4- Tapering Arm	—	0.2 units on a scale Standard Deviation 0.49	—
Mean Change From Double-blind Baseline in Health Assessment Questionnaire- Disability Index (HAQ-DI) Score Over Time Flare Week 4- Withdrawal Arm	—	0.2 units on a scale Standard Deviation 0.35	—
Mean Change From Double-blind Baseline in Health Assessment Questionnaire- Disability Index (HAQ-DI) Score Over Time Flare Week 10- Tapering Arm	—	0.1 units on a scale Standard Deviation 0.24	—
Mean Change From Double-blind Baseline in Health Assessment Questionnaire- Disability Index (HAQ-DI) Score Over Time Flare Week 10- Withdrawal Arm	—	0.1 units on a scale Standard Deviation 0.20	—
Mean Change From Double-blind Baseline in Health Assessment Questionnaire- Disability Index (HAQ-DI) Score Over Time Flare Week 16- Tapering Arm	—	0.2 units on a scale Standard Deviation 0.39	—
Mean Change From Double-blind Baseline in Health Assessment Questionnaire- Disability Index (HAQ-DI) Score Over Time Flare Week 16- Withdrawal Arm	—	0.1 units on a scale Standard Deviation 0.24	—

SECONDARY outcome

Timeframe: Week 4 and Week 40

Population: Double-blind Treated Subject population: participants who received at least 1 dose of study drug during the Double-blind period and had at least Double-blind Baseline data for this endpoint

The Health Assessment Questionnaire - Disability Index (HAQ-DI) is a participant-reported questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task were summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. The number of participants with HAQ-DI score ≤ 0.5 (considered to be normal) was recorded.

Outcome measures

Outcome measures
Measure	Non-Flared Participants n=76 Participants Participants who did not experience flare during the Double-blind Period	Flared Participants n=46 Participants Participants who experienced flare during the Double-blind Period	CDAI ≤ 2.8 Clinical Disease Activity Index (CDAI) score ≤ 2.8
Number of Participants With Health Assessment Questionnaire- Disability Index (HAQ-DI) Score ≤ 0.5 at Double-blind Baseline and at Week 40 Double Blind Week 4- Tapering Arm	50 Participants	21 Participants	—
Number of Participants With Health Assessment Questionnaire- Disability Index (HAQ-DI) Score ≤ 0.5 at Double-blind Baseline and at Week 40 Double Blind Week 4- Withdrawal Arm	10 Participants	7 Participants	—
Number of Participants With Health Assessment Questionnaire- Disability Index (HAQ-DI) Score ≤ 0.5 at Double-blind Baseline and at Week 40 Double Blind Week 40- Tapering Arm	48 Participants	2 Participants	—
Number of Participants With Health Assessment Questionnaire- Disability Index (HAQ-DI) Score ≤ 0.5 at Double-blind Baseline and at Week 40 Double Blind Week 40- Withdrawal Arm	9 Participants	0 Participants	—

SECONDARY outcome

Timeframe: From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16

Population: Double-blind Treated Subject population: participants who received at least 1 dose of study drug during the Double-blind period and had at least Double-blind Baseline data for this endpoint

The RAPID3 is an activity index derived from the Multi-dimensional Health Assessment Questionnaire (MD-HAQ). It includes an assessment of physical function, a pain Visual Analog Scale (VAS), and a participant global assessment of disease activity VAS. The total RAPID3 score ranges from 0 to 30 where higher scores represent severe disease. Negative values indicate improvement from the Double-blind baseline score.

Outcome measures

Outcome measures
Measure	Non-Flared Participants n=76 Participants Participants who did not experience flare during the Double-blind Period	Flared Participants n=46 Participants Participants who experienced flare during the Double-blind Period	CDAI ≤ 2.8 Clinical Disease Activity Index (CDAI) score ≤ 2.8
Mean Change From Double-blind Baseline in Routine Assessment of Patient Index Data (RAPID3) Questionnaire Scores Assessed During In-office Visits Double Blind Week 10- Tapering Arm	0.7 units on a scale Standard Deviation 3.20	1.9 units on a scale Standard Deviation 3.92	—
Mean Change From Double-blind Baseline in Routine Assessment of Patient Index Data (RAPID3) Questionnaire Scores Assessed During In-office Visits Double Blind Week 10- Withdrawal Arm	1.5 units on a scale Standard Deviation 4.67	1.4 units on a scale Standard Deviation 3.73	—
Mean Change From Double-blind Baseline in Routine Assessment of Patient Index Data (RAPID3) Questionnaire Scores Assessed During In-office Visits Double Blind Week 16- Tapering Arm	0.8 units on a scale Standard Deviation 2.80	4.7 units on a scale Standard Deviation 5.66	—
Mean Change From Double-blind Baseline in Routine Assessment of Patient Index Data (RAPID3) Questionnaire Scores Assessed During In-office Visits Double Blind Week 16- Withdrawal Arm	0.1 units on a scale Standard Deviation 1.37	2.5 units on a scale Standard Deviation 4.59	—
Mean Change From Double-blind Baseline in Routine Assessment of Patient Index Data (RAPID3) Questionnaire Scores Assessed During In-office Visits Double Blind Week 22- Tapering Arm	0.3 units on a scale Standard Deviation 2.83	2.6 units on a scale Standard Deviation 4.83	—
Mean Change From Double-blind Baseline in Routine Assessment of Patient Index Data (RAPID3) Questionnaire Scores Assessed During In-office Visits Double Blind Week 22- Withdrawal arm	0.6 units on a scale Standard Deviation 3.31	3.6 units on a scale Standard Deviation 4.18	—
Mean Change From Double-blind Baseline in Routine Assessment of Patient Index Data (RAPID3) Questionnaire Scores Assessed During In-office Visits Double Blind Week 28- Tapering arm	0.6 units on a scale Standard Deviation 2.47	2.2 units on a scale Standard Deviation 4.20	—
Mean Change From Double-blind Baseline in Routine Assessment of Patient Index Data (RAPID3) Questionnaire Scores Assessed During In-office Visits Double Blind Week 28- Withdrawal Arm	-0.3 units on a scale Standard Deviation 1.61	3.7 units on a scale Standard Deviation 4.45	—
Mean Change From Double-blind Baseline in Routine Assessment of Patient Index Data (RAPID3) Questionnaire Scores Assessed During In-office Visits Double Blind Week 34- Tapering Arm	-0.0 units on a scale Standard Deviation 1.93	2.2 units on a scale Standard Deviation 3.77	—
Mean Change From Double-blind Baseline in Routine Assessment of Patient Index Data (RAPID3) Questionnaire Scores Assessed During In-office Visits Double Blind Week 34- Withdrawal Arm	1.6 units on a scale Standard Deviation 2.33	1.9 units on a scale Standard Deviation 2.62	—
Mean Change From Double-blind Baseline in Routine Assessment of Patient Index Data (RAPID3) Questionnaire Scores Assessed During In-office Visits Double Blind Week 40- Tapering Arm	0.0 units on a scale Standard Deviation 2.39	4.7 units on a scale Standard Deviation 6.22	—
Mean Change From Double-blind Baseline in Routine Assessment of Patient Index Data (RAPID3) Questionnaire Scores Assessed During In-office Visits Double Blind Week 40- Withdrawal Arm	0.8 units on a scale Standard Deviation 1.62	0.4 units on a scale Standard Deviation 0.92	—
Mean Change From Double-blind Baseline in Routine Assessment of Patient Index Data (RAPID3) Questionnaire Scores Assessed During In-office Visits Flare Week 0- Tapering Arm	—	6.1 units on a scale Standard Deviation 6.64	—
Mean Change From Double-blind Baseline in Routine Assessment of Patient Index Data (RAPID3) Questionnaire Scores Assessed During In-office Visits Flare Week 0- Withdrawal Arm	—	3.9 units on a scale Standard Deviation 5.60	—
Mean Change From Double-blind Baseline in Routine Assessment of Patient Index Data (RAPID3) Questionnaire Scores Assessed During In-office Visits Flare Week 4- Tapering Arm	—	3.1 units on a scale Standard Deviation 5.38	—
Mean Change From Double-blind Baseline in Routine Assessment of Patient Index Data (RAPID3) Questionnaire Scores Assessed During In-office Visits Flare Week 4- Withdrawal Arm	—	3.2 units on a scale Standard Deviation 4.15	—
Mean Change From Double-blind Baseline in Routine Assessment of Patient Index Data (RAPID3) Questionnaire Scores Assessed During In-office Visits Flare Week 10- Tapering Arm	—	2.8 units on a scale Standard Deviation 3.93	—
Mean Change From Double-blind Baseline in Routine Assessment of Patient Index Data (RAPID3) Questionnaire Scores Assessed During In-office Visits Flare Week 10- Withdrawal Arm	—	2.3 units on a scale Standard Deviation 2.61	—
Mean Change From Double-blind Baseline in Routine Assessment of Patient Index Data (RAPID3) Questionnaire Scores Assessed During In-office Visits Flare Week 16- Tapering Arm	—	2.9 units on a scale Standard Deviation 4.22	—
Mean Change From Double-blind Baseline in Routine Assessment of Patient Index Data (RAPID3) Questionnaire Scores Assessed During In-office Visits Flare Week 16- Withdrawal Arm	—	2.1 units on a scale Standard Deviation 3.01	—

SECONDARY outcome

Timeframe: Flare Week 0 and Flare Weeks 1, 2, 3, 5, 6, 7, 8, 9, 11, 12, 13, 14, 15

Population: All Open-label rescue treated participants with available data; last observation carried forward

The RAPID3 is an activity index derived from the Multi-dimensional Health Assessment Questionnaire (MD-HAQ). It includes an assessment of physical function, a pain Visual Analog Scale (VAS), and a participant global assessment of disease activity VAS. The total RAPID3 score ranges from 0 to 30 where higher scores represent severe disease. Negative values indicate improvement from the Double-blind baseline score.

Outcome measures

Outcome measures
Measure	Non-Flared Participants Participants who did not experience flare during the Double-blind Period	Flared Participants n=33 Participants Participants who experienced flare during the Double-blind Period	CDAI ≤ 2.8 Clinical Disease Activity Index (CDAI) score ≤ 2.8
Mean Change From Flare Week 0 in Routine Assessment of Patient Index Data (RAPID3) Questionnaire Scores Assessed at Home Flare Week 1- Tapering Arm	—	-1.6 units on a scale Standard Deviation 4.92	—
Mean Change From Flare Week 0 in Routine Assessment of Patient Index Data (RAPID3) Questionnaire Scores Assessed at Home Flare Week 1- Withdrawal Arm	—	3.7 units on a scale Standard Deviation 7.20	—
Mean Change From Flare Week 0 in Routine Assessment of Patient Index Data (RAPID3) Questionnaire Scores Assessed at Home Flare Week 2- Tapering Arm	—	-3.1 units on a scale Standard Deviation 5.41	—
Mean Change From Flare Week 0 in Routine Assessment of Patient Index Data (RAPID3) Questionnaire Scores Assessed at Home Flare Week 2- Withdrawal Arm	—	0.8 units on a scale Standard Deviation 6.89	—
Mean Change From Flare Week 0 in Routine Assessment of Patient Index Data (RAPID3) Questionnaire Scores Assessed at Home Flare Week 3- Tapering Arm	—	-3.8 units on a scale Standard Deviation 6.78	—
Mean Change From Flare Week 0 in Routine Assessment of Patient Index Data (RAPID3) Questionnaire Scores Assessed at Home Flare Week 3- Withdrawal Arm	—	-0.4 units on a scale Standard Deviation 7.94	—
Mean Change From Flare Week 0 in Routine Assessment of Patient Index Data (RAPID3) Questionnaire Scores Assessed at Home Flare Week 5- Tapering Arm	—	-3.8 units on a scale Standard Deviation 6.61	—
Mean Change From Flare Week 0 in Routine Assessment of Patient Index Data (RAPID3) Questionnaire Scores Assessed at Home Flare Week 5- Withdrawal Arm	—	-0.8 units on a scale Standard Deviation 6.56	—
Mean Change From Flare Week 0 in Routine Assessment of Patient Index Data (RAPID3) Questionnaire Scores Assessed at Home Flare Week 6- Tapering Arm	—	-4.1 units on a scale Standard Deviation 6.81	—
Mean Change From Flare Week 0 in Routine Assessment of Patient Index Data (RAPID3) Questionnaire Scores Assessed at Home Flare Week 6- Withdrawal Arm	—	-0.9 units on a scale Standard Deviation 6.97	—
Mean Change From Flare Week 0 in Routine Assessment of Patient Index Data (RAPID3) Questionnaire Scores Assessed at Home Flare Week 7- Tapering Arm	—	-3.7 units on a scale Standard Deviation 6.86	—
Mean Change From Flare Week 0 in Routine Assessment of Patient Index Data (RAPID3) Questionnaire Scores Assessed at Home Flare Week 7- Withdrawal Arm	—	-0.6 units on a scale Standard Deviation 6.26	—
Mean Change From Flare Week 0 in Routine Assessment of Patient Index Data (RAPID3) Questionnaire Scores Assessed at Home Flare Week 8- Tapering Arm	—	-4.4 units on a scale Standard Deviation 7.17	—
Mean Change From Flare Week 0 in Routine Assessment of Patient Index Data (RAPID3) Questionnaire Scores Assessed at Home Flare Week 8- Withdrawal Arm	—	-0.6 units on a scale Standard Deviation 5.56	—
Mean Change From Flare Week 0 in Routine Assessment of Patient Index Data (RAPID3) Questionnaire Scores Assessed at Home Flare Week 9- Tapering Arm	—	-3.3 units on a scale Standard Deviation 5.81	—
Mean Change From Flare Week 0 in Routine Assessment of Patient Index Data (RAPID3) Questionnaire Scores Assessed at Home Flare Week 9- Withdrawal Arm	—	-1.0 units on a scale Standard Deviation 5.89	—
Mean Change From Flare Week 0 in Routine Assessment of Patient Index Data (RAPID3) Questionnaire Scores Assessed at Home Flare Week 11- Tapering Arm	—	-3.7 units on a scale Standard Deviation 5.69	—
Mean Change From Flare Week 0 in Routine Assessment of Patient Index Data (RAPID3) Questionnaire Scores Assessed at Home Flare Week 11- Withdrawal Arm	—	-1.0 units on a scale Standard Deviation 5.85	—
Mean Change From Flare Week 0 in Routine Assessment of Patient Index Data (RAPID3) Questionnaire Scores Assessed at Home Flare Week 12- Tapering Arm	—	-3.4 units on a scale Standard Deviation 5.84	—
Mean Change From Flare Week 0 in Routine Assessment of Patient Index Data (RAPID3) Questionnaire Scores Assessed at Home Flare Week 12- Withdrawal Arm	—	-2.3 units on a scale Standard Deviation 4.46	—
Mean Change From Flare Week 0 in Routine Assessment of Patient Index Data (RAPID3) Questionnaire Scores Assessed at Home Flare Week 13- Tapering Arm	—	-3.5 units on a scale Standard Deviation 5.72	—
Mean Change From Flare Week 0 in Routine Assessment of Patient Index Data (RAPID3) Questionnaire Scores Assessed at Home Flare Week 13- Withdrawal Arm	—	-2.5 units on a scale Standard Deviation 4.78	—
Mean Change From Flare Week 0 in Routine Assessment of Patient Index Data (RAPID3) Questionnaire Scores Assessed at Home Flare Week 14- Tapering Arm	—	-3.1 units on a scale Standard Deviation 5.54	—
Mean Change From Flare Week 0 in Routine Assessment of Patient Index Data (RAPID3) Questionnaire Scores Assessed at Home Flare Week 14- Withdrawal Arm	—	-2.4 units on a scale Standard Deviation 4.79	—
Mean Change From Flare Week 0 in Routine Assessment of Patient Index Data (RAPID3) Questionnaire Scores Assessed at Home Flare Week 15- Tapering Arm	—	-3.5 units on a scale Standard Deviation 6.69	—
Mean Change From Flare Week 0 in Routine Assessment of Patient Index Data (RAPID3) Questionnaire Scores Assessed at Home Flare Week 15- Withdrawal Arm	—	-2.2 units on a scale Standard Deviation 4.70	—

SECONDARY outcome

Timeframe: From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16

Population: Double-blind Treated Subject population: participants who received at least 1 dose of study drug during the Double-blind period and had at least Double-blind Baseline data for this endpoint

Twenty-eight joints, excluding hip joints, were assessed for swelling by physical examination. Swelling of each joint was classified as present (1) or absent (0), for a total possible score of 0 (0 joints with swelling) to 28 (worst possible score/28 joints with swelling). Negative values indicate improvement from baseline.

Outcome measures

SECONDARY outcome

Timeframe: From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16

Population: Double-blind Treated Subject population: participants who received at least 1 dose of study drug during the Double-blind period and had at least Double-blind Baseline data for this endpoint

Sixty-six joints were assessed for swelling by physical examination. Swelling of each joint was classified as present (1) or absent (0), for a total possible score of 0 (0 joints with swelling) to 66 (worst possible score/66 joints with swelling). Negative values indicate improvement from baseline.

Outcome measures

SECONDARY outcome

Timeframe: From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16

Population: Double-blind Treated Subject population: participants who received at least 1 dose of study drug during the Double-blind period and had at least Double-blind Baseline data for this endpoint

Twenty-eight joints were assessed for tenderness by physical examination. Pain or tenderness of each joint was classified as present (1) or absent (0), for a total possible score of 0 (0 joints with tenderness) to 28 (worst possible score/28 joints with tenderness). Negative values indicate improvement from baseline.

Outcome measures

SECONDARY outcome

Timeframe: From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16

Population: Double-blind Treated Subject population: participants who received at least 1 dose of study drug during the Double-blind period and had at least Double-blind Baseline data for this endpoint

Sixty-eight joints were assessed for tenderness by physical examination. Pain or tenderness of each joint was classified as present (1) or absent (0), for a total possible score of 0 (0 joints with tenderness) to 68 (worst possible score/68 joints with tenderness). Negative values indicate improvement from baseline.

Outcome measures

SECONDARY outcome

Timeframe: From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16

Population: Double-blind Treated Subject population: participants who received at least 1 dose of study drug during the Double-blind period and had at least Double-blind Baseline data for this endpoint

Participants rated the severity of their rheumatoid arthritis symptoms and how well they were doing during the last 24 hours by placing a vertical mark on a line with a range of 0 (very well) to 100 mm (very poorly). Negative values indicate improvement from baseline.

Outcome measures

Outcome measures
Measure	Non-Flared Participants n=76 Participants Participants who did not experience flare during the Double-blind Period	Flared Participants n=46 Participants Participants who experienced flare during the Double-blind Period	CDAI ≤ 2.8 Clinical Disease Activity Index (CDAI) score ≤ 2.8
Mean Change From Double-blind Baseline in Participant's Global Assessment of Disease Activity Double Blind Week 10- Tapering Arm	2.6 units on a scale Standard Deviation 8.49	11.6 units on a scale Standard Deviation 19.00	—
Mean Change From Double-blind Baseline in Participant's Global Assessment of Disease Activity Double Blind Week 10- Withdrawal Arm	9.6 units on a scale Standard Deviation 20.27	8.0 units on a scale Standard Deviation 21.66	—
Mean Change From Double-blind Baseline in Participant's Global Assessment of Disease Activity Double Blind Week 16- Tapering Arm	2.4 units on a scale Standard Deviation 9.27	20.5 units on a scale Standard Deviation 26.97	—
Mean Change From Double-blind Baseline in Participant's Global Assessment of Disease Activity Double Blind Week 16- Withdrawal Arm	-0.3 units on a scale Standard Deviation 5.76	10.7 units on a scale Standard Deviation 19.97	—
Mean Change From Double-blind Baseline in Participant's Global Assessment of Disease Activity Double Blind Week 22- Tapering Arm	1.7 units on a scale Standard Deviation 9.14	10.7 units on a scale Standard Deviation 17.74	—
Mean Change From Double-blind Baseline in Participant's Global Assessment of Disease Activity Double Blind Week 22- Withdrawal arm	0.2 units on a scale Standard Deviation 8.87	5.8 units on a scale Standard Deviation 8.73	—
Mean Change From Double-blind Baseline in Participant's Global Assessment of Disease Activity Double Blind Week 28- Tapering arm	2.7 units on a scale Standard Deviation 10.03	9.4 units on a scale Standard Deviation 21.03	—
Mean Change From Double-blind Baseline in Participant's Global Assessment of Disease Activity Double Blind Week 28- Withdrawal Arm	-1.0 units on a scale Standard Deviation 7.82	15.0 units on a scale Standard Deviation 25.76	—
Mean Change From Double-blind Baseline in Participant's Global Assessment of Disease Activity Double Blind Week 34- Tapering Arm	1.2 units on a scale Standard Deviation 7.23	11.5 units on a scale Standard Deviation 13.70	—
Mean Change From Double-blind Baseline in Participant's Global Assessment of Disease Activity Double Blind Week 34- Withdrawal Arm	0.7 units on a scale Standard Deviation 7.25	-1.0 units on a scale Standard Deviation 1.41	—
Mean Change From Double-blind Baseline in Participant's Global Assessment of Disease Activity Double Blind Week 40- Tapering Arm	0.0 units on a scale Standard Deviation 7.60	22.9 units on a scale Standard Deviation 35.32	—
Mean Change From Double-blind Baseline in Participant's Global Assessment of Disease Activity Double Blind Week 40- Withdrawal Arm	-1.7 units on a scale Standard Deviation 4.45	2.0 units on a scale Standard Deviation 9.90	—
Mean Change From Double-blind Baseline in Participant's Global Assessment of Disease Activity Flare Week 0- Tapering Arm	—	29.5 units on a scale Standard Deviation 29.43	—
Mean Change From Double-blind Baseline in Participant's Global Assessment of Disease Activity Flare Week 0- Withdrawal Arm	—	21.6 units on a scale Standard Deviation 27.07	—
Mean Change From Double-blind Baseline in Participant's Global Assessment of Disease Activity Flare Week 4- Tapering Arm	—	13.7 units on a scale Standard Deviation 22.93	—
Mean Change From Double-blind Baseline in Participant's Global Assessment of Disease Activity Flare Week 4- Withdrawal Arm	—	11.7 units on a scale Standard Deviation 21.96	—
Mean Change From Double-blind Baseline in Participant's Global Assessment of Disease Activity Flare Week 10- Tapering Arm	—	11.7 units on a scale Standard Deviation 16.89	—
Mean Change From Double-blind Baseline in Participant's Global Assessment of Disease Activity Flare Week 10- Withdrawal Arm	—	14.1 units on a scale Standard Deviation 10.35	—
Mean Change From Double-blind Baseline in Participant's Global Assessment of Disease Activity Flare Week 16- Tapering Arm	—	9.4 units on a scale Standard Deviation 13.47	—
Mean Change From Double-blind Baseline in Participant's Global Assessment of Disease Activity Flare Week 16- Withdrawal Arm	—	6.9 units on a scale Standard Deviation 9.31	—

SECONDARY outcome

Timeframe: From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16

Population: Double-blind Treated Subject population: participants who received at least 1 dose of study drug during the Double-blind period and had at least Double-blind Baseline data for this endpoint

Participants rated the severity of their rheumatoid arthritis pain in the past week by placing a vertical mark on a line with a range of 0 (no pain) to 100 mm (severe pain). Negative values indicate improvement from baseline.

Outcome measures

Outcome measures
Measure	Non-Flared Participants n=76 Participants Participants who did not experience flare during the Double-blind Period	Flared Participants n=46 Participants Participants who experienced flare during the Double-blind Period	CDAI ≤ 2.8 Clinical Disease Activity Index (CDAI) score ≤ 2.8
Mean Change From Double-blind Baseline in Participant's Global Assessment of Rheumatoid Arthritis Pain Double Blind Week 10- Tapering Arm	3.5 units on a scale Standard Deviation 14.33	8.0 units on a scale Standard Deviation 17.96	—
Mean Change From Double-blind Baseline in Participant's Global Assessment of Rheumatoid Arthritis Pain Double Blind Week 10- Withdrawal Arm	9.3 units on a scale Standard Deviation 21.04	6.4 units on a scale Standard Deviation 19.05	—
Mean Change From Double-blind Baseline in Participant's Global Assessment of Rheumatoid Arthritis Pain Double Blind Week 16- Tapering Arm	3.0 units on a scale Standard Deviation 12.48	17.8 units on a scale Standard Deviation 27.16	—
Mean Change From Double-blind Baseline in Participant's Global Assessment of Rheumatoid Arthritis Pain Double Blind Week 16- Withdrawal Arm	-0.6 units on a scale Standard Deviation 9.65	10.7 units on a scale Standard Deviation 18.93	—
Mean Change From Double-blind Baseline in Participant's Global Assessment of Rheumatoid Arthritis Pain Double Blind Week 22- Tapering Arm	0.3 units on a scale Standard Deviation 7.82	10.4 units on a scale Standard Deviation 19.55	—
Mean Change From Double-blind Baseline in Participant's Global Assessment of Rheumatoid Arthritis Pain Double Blind Week 22- Withdrawal arm	-1.1 units on a scale Standard Deviation 11.20	4.0 units on a scale Standard Deviation 4.90	—
Mean Change From Double-blind Baseline in Participant's Global Assessment of Rheumatoid Arthritis Pain Double Blind Week 28- Tapering arm	1.6 units on a scale Standard Deviation 9.83	8.3 units on a scale Standard Deviation 17.57	—
Mean Change From Double-blind Baseline in Participant's Global Assessment of Rheumatoid Arthritis Pain Double Blind Week 28- Withdrawal Arm	-1.4 units on a scale Standard Deviation 10.93	14.0 units on a scale Standard Deviation 24.59	—
Mean Change From Double-blind Baseline in Participant's Global Assessment of Rheumatoid Arthritis Pain Double Blind Week 34- Tapering Arm	-0.3 units on a scale Standard Deviation 7.61	11.6 units on a scale Standard Deviation 14.61	—
Mean Change From Double-blind Baseline in Participant's Global Assessment of Rheumatoid Arthritis Pain Double Blind Week 34- Withdrawal Arm	2.1 units on a scale Standard Deviation 8.40	-3.5 units on a scale Standard Deviation 2.12	—
Mean Change From Double-blind Baseline in Participant's Global Assessment of Rheumatoid Arthritis Pain Double Blind Week 40- Tapering Arm	-0.5 units on a scale Standard Deviation 10.00	24.0 units on a scale Standard Deviation 32.67	—
Mean Change From Double-blind Baseline in Participant's Global Assessment of Rheumatoid Arthritis Pain Double Blind Week 40- Withdrawal Arm	-0.9 units on a scale Standard Deviation 5.07	-0.5 units on a scale Standard Deviation 20.51	—
Mean Change From Double-blind Baseline in Participant's Global Assessment of Rheumatoid Arthritis Pain Flare Week 0- Tapering Arm	—	24.4 units on a scale Standard Deviation 31.66	—
Mean Change From Double-blind Baseline in Participant's Global Assessment of Rheumatoid Arthritis Pain Flare Week 0- Withdrawal Arm	—	17.0 units on a scale Standard Deviation 19.38	—
Mean Change From Double-blind Baseline in Participant's Global Assessment of Rheumatoid Arthritis Pain Flare Week 4- Tapering Arm	—	9.0 units on a scale Standard Deviation 21.68	—
Mean Change From Double-blind Baseline in Participant's Global Assessment of Rheumatoid Arthritis Pain Flare Week 4- Withdrawal Arm	—	11.1 units on a scale Standard Deviation 17.46	—
Mean Change From Double-blind Baseline in Participant's Global Assessment of Rheumatoid Arthritis Pain Flare Week 10- Tapering Arm	—	7.5 units on a scale Standard Deviation 14.93	—
Mean Change From Double-blind Baseline in Participant's Global Assessment of Rheumatoid Arthritis Pain Flare Week 10- Withdrawal Arm	—	8.3 units on a scale Standard Deviation 9.60	—
Mean Change From Double-blind Baseline in Participant's Global Assessment of Rheumatoid Arthritis Pain Flare Week 16- Tapering Arm	—	8.0 units on a scale Standard Deviation 14.41	—
Mean Change From Double-blind Baseline in Participant's Global Assessment of Rheumatoid Arthritis Pain Flare Week 16- Withdrawal Arm	—	4.3 units on a scale Standard Deviation 6.32	—

SECONDARY outcome

Timeframe: From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16

Population: Double-blind Treated Subject population: participants who received at least 1 dose of study drug during the Double-blind period and had at least Double-blind Baseline data for this endpoint

Physicians assessed participants' current rheumatoid arthritis disease activity at the time of the visit (independent of the participant's self-assessment) by placing a vertical mark on a line with a range of 0 (very low) to 100 mm (very high). Negative values indicate improvement from baseline.

Outcome measures

Outcome measures
Measure	Non-Flared Participants n=76 Participants Participants who did not experience flare during the Double-blind Period	Flared Participants n=46 Participants Participants who experienced flare during the Double-blind Period	CDAI ≤ 2.8 Clinical Disease Activity Index (CDAI) score ≤ 2.8
Mean Change From Double-blind Baseline in Physician's Global Assessment of Disease Activity Double Blind Week 10- Tapering Arm	1.3 units on a scale Standard Deviation 4.27	10.2 units on a scale Standard Deviation 19.54	—
Mean Change From Double-blind Baseline in Physician's Global Assessment of Disease Activity Double Blind Week 10- Withdrawal Arm	0.5 units on a scale Standard Deviation 4.74	1.6 units on a scale Standard Deviation 4.67	—
Mean Change From Double-blind Baseline in Physician's Global Assessment of Disease Activity Double Blind Week 16- Tapering Arm	0.9 units on a scale Standard Deviation 5.07	13.2 units on a scale Standard Deviation 21.48	—
Mean Change From Double-blind Baseline in Physician's Global Assessment of Disease Activity Double Blind Week 16- Withdrawal Arm	-0.5 units on a scale Standard Deviation 2.98	5.0 units on a scale Standard Deviation 3.35	—
Mean Change From Double-blind Baseline in Physician's Global Assessment of Disease Activity Double Blind Week 22- Tapering Arm	0.9 units on a scale Standard Deviation 5.05	6.9 units on a scale Standard Deviation 14.83	—
Mean Change From Double-blind Baseline in Physician's Global Assessment of Disease Activity Double Blind Week 22- Withdrawal arm	0.4 units on a scale Standard Deviation 3.26	3.8 units on a scale Standard Deviation 2.87	—
Mean Change From Double-blind Baseline in Physician's Global Assessment of Disease Activity Double Blind Week 28- Tapering arm	1.7 units on a scale Standard Deviation 5.51	7.3 units on a scale Standard Deviation 16.51	—
Mean Change From Double-blind Baseline in Physician's Global Assessment of Disease Activity Double Blind Week 28- Withdrawal Arm	-0.9 units on a scale Standard Deviation 2.74	10.0 units on a scale Standard Deviation 10.89	—
Mean Change From Double-blind Baseline in Physician's Global Assessment of Disease Activity Double Blind Week 34- Tapering Arm	0.8 units on a scale Standard Deviation 3.60	5.5 units on a scale Standard Deviation 12.27	—
Mean Change From Double-blind Baseline in Physician's Global Assessment of Disease Activity Double Blind Week 34- Withdrawal Arm	0.6 units on a scale Standard Deviation 4.13	0.0 units on a scale Standard Deviation 0.00	—
Mean Change From Double-blind Baseline in Physician's Global Assessment of Disease Activity Double Blind Week 40- Tapering Arm	1.0 units on a scale Standard Deviation 5.32	16.2 units on a scale Standard Deviation 26.91	—
Mean Change From Double-blind Baseline in Physician's Global Assessment of Disease Activity Double Blind Week 40- Withdrawal Arm	-0.6 units on a scale Standard Deviation 2.42	19.5 units on a scale Standard Deviation 26.16	—
Mean Change From Double-blind Baseline in Physician's Global Assessment of Disease Activity Flare Week 0- Tapering Arm	—	26.5 units on a scale Standard Deviation 23.28	—
Mean Change From Double-blind Baseline in Physician's Global Assessment of Disease Activity Flare Week 0- Withdrawal Arm	—	17.4 units on a scale Standard Deviation 15.37	—
Mean Change From Double-blind Baseline in Physician's Global Assessment of Disease Activity Flare Week 4- Tapering Arm	—	12.2 units on a scale Standard Deviation 17.06	—
Mean Change From Double-blind Baseline in Physician's Global Assessment of Disease Activity Flare Week 4- Withdrawal Arm	—	9.3 units on a scale Standard Deviation 20.27	—
Mean Change From Double-blind Baseline in Physician's Global Assessment of Disease Activity Flare Week 10- Tapering Arm	—	10.2 units on a scale Standard Deviation 13.82	—
Mean Change From Double-blind Baseline in Physician's Global Assessment of Disease Activity Flare Week 10- Withdrawal Arm	—	12.9 units on a scale Standard Deviation 11.51	—
Mean Change From Double-blind Baseline in Physician's Global Assessment of Disease Activity Flare Week 16- Tapering Arm	—	8.6 units on a scale Standard Deviation 12.48	—
Mean Change From Double-blind Baseline in Physician's Global Assessment of Disease Activity Flare Week 16- Withdrawal Arm	—	7.6 units on a scale Standard Deviation 20.00	—

SECONDARY outcome

Timeframe: From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16

Population: Double-blind Treated Subject population: participants who received at least 1 dose of study drug during the Double-blind period and had at least Double-blind Baseline data for this endpoint

The duration of morning stiffness was reported by participants as the average daily length during the past week in minutes (from time of awaking to time of maximal improvement). Negative values indicate improvement from baseline.

Outcome measures

Outcome measures
Measure	Non-Flared Participants n=74 Participants Participants who did not experience flare during the Double-blind Period	Flared Participants n=45 Participants Participants who experienced flare during the Double-blind Period	CDAI ≤ 2.8 Clinical Disease Activity Index (CDAI) score ≤ 2.8
Mean Change From Double-blind Baseline in Morning Stiffness Duration Double Blind Week 10- Tapering Arm	1.8 minutes Standard Deviation 7.19	3.5 minutes Standard Deviation 17.33	—
Mean Change From Double-blind Baseline in Morning Stiffness Duration Double Blind Week 10- Withdrawal Arm	1.5 minutes Standard Deviation 5.97	1.1 minutes Standard Deviation 3.60	—
Mean Change From Double-blind Baseline in Morning Stiffness Duration Double Blind Week 16- Tapering Arm	2.3 minutes Standard Deviation 12.54	6.6 minutes Standard Deviation 24.41	—
Mean Change From Double-blind Baseline in Morning Stiffness Duration Double Blind Week 16- Withdrawal Arm	-0.6 minutes Standard Deviation 5.05	9.2 minutes Standard Deviation 19.78	—
Mean Change From Double-blind Baseline in Morning Stiffness Duration Double Blind Week 22- Tapering Arm	1.5 minutes Standard Deviation 9.67	-1.6 minutes Standard Deviation 8.07	—
Mean Change From Double-blind Baseline in Morning Stiffness Duration Double Blind Week 22- Withdrawal arm	0.5 minutes Standard Deviation 3.70	1.0 minutes Standard Deviation 2.00	—
Mean Change From Double-blind Baseline in Morning Stiffness Duration Double Blind Week 28- Tapering arm	2.4 minutes Standard Deviation 10.53	2.6 minutes Standard Deviation 13.09	—
Mean Change From Double-blind Baseline in Morning Stiffness Duration Double Blind Week 28- Withdrawal Arm	0.0 minutes Standard Deviation 3.71	17.3 minutes Standard Deviation 28.81	—
Mean Change From Double-blind Baseline in Morning Stiffness Duration Double Blind Week 34- Tapering Arm	1.4 minutes Standard Deviation 8.86	0.6 minutes Standard Deviation 10.97	—
Mean Change From Double-blind Baseline in Morning Stiffness Duration Double Blind Week 34- Withdrawal Arm	-1.1 minutes Standard Deviation 6.64	0.0 minutes Standard Deviation 0.00	—
Mean Change From Double-blind Baseline in Morning Stiffness Duration Double Blind Week 40- Tapering Arm	0.4 minutes Standard Deviation 9.33	2.0 minutes Standard Deviation 12.49	—
Mean Change From Double-blind Baseline in Morning Stiffness Duration Double Blind Week 40- Withdrawal Arm	-0.2 minutes Standard Deviation 5.78	0.0 minutes Standard Deviation 0.00	—
Mean Change From Double-blind Baseline in Morning Stiffness Duration Flare Week 0- Tapering Arm	—	13.5 minutes Standard Deviation 25.21	—
Mean Change From Double-blind Baseline in Morning Stiffness Duration Flare Week 0- Withdrawal Arm	—	18.5 minutes Standard Deviation 26.25	—
Mean Change From Double-blind Baseline in Morning Stiffness Duration Flare Week 4- Tapering Arm	—	25.0 minutes Standard Deviation 110.77	—
Mean Change From Double-blind Baseline in Morning Stiffness Duration Flare Week 4- Withdrawal Arm	—	19.9 minutes Standard Deviation 26.51	—
Mean Change From Double-blind Baseline in Morning Stiffness Duration Flare Week 10- Tapering Arm	—	8.1 minutes Standard Deviation 30.20	—
Mean Change From Double-blind Baseline in Morning Stiffness Duration Flare Week 10- Withdrawal Arm	—	7.9 minutes Standard Deviation 9.72	—
Mean Change From Double-blind Baseline in Morning Stiffness Duration Flare Week 16- Tapering Arm	—	17.3 minutes Standard Deviation 36.46	—
Mean Change From Double-blind Baseline in Morning Stiffness Duration Flare Week 16- Withdrawal Arm	—	9.6 minutes Standard Deviation 20.65	—

SECONDARY outcome

Timeframe: From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16

Population: Double-blind Treated Subject population: participants who received at least 1 dose of study drug during the Double-blind period and had at least Double-blind Baseline data for this endpoint

Morning stiffness severity was assessed by a numeric rating-scale (NRS). Participants rated the severity of morning stiffness during the past week from 0 to 10 with 0 representing "not severe" and 10 "very severe". Negative values indicate improvement from baseline.

Outcome measures

Outcome measures
Measure	Non-Flared Participants n=76 Participants Participants who did not experience flare during the Double-blind Period	Flared Participants n=46 Participants Participants who experienced flare during the Double-blind Period	CDAI ≤ 2.8 Clinical Disease Activity Index (CDAI) score ≤ 2.8
Mean Change From Double-blind Baseline in Morning Stiffness Severity Double Blind Week 10- Tapering Arm	0.4 units on a scale Standard Deviation 1.01	0.6 units on a scale Standard Deviation 1.51	—
Mean Change From Double-blind Baseline in Morning Stiffness Severity Double Blind Week 10- Withdrawal Arm	0.6 units on a scale Standard Deviation 1.29	0.4 units on a scale Standard Deviation 1.81	—
Mean Change From Double-blind Baseline in Morning Stiffness Severity Double Blind Week 16- Tapering Arm	0.3 units on a scale Standard Deviation 1.11	0.8 units on a scale Standard Deviation 1.73	—
Mean Change From Double-blind Baseline in Morning Stiffness Severity Double Blind Week 16- Withdrawal Arm	-0.1 units on a scale Standard Deviation 1.04	0.7 units on a scale Standard Deviation 2.24	—
Mean Change From Double-blind Baseline in Morning Stiffness Severity Double Blind Week 22- Tapering Arm	0.2 units on a scale Standard Deviation 0.85	0.9 units on a scale Standard Deviation 1.27	—
Mean Change From Double-blind Baseline in Morning Stiffness Severity Double Blind Week 22- Withdrawal arm	0.4 units on a scale Standard Deviation 1.75	0.8 units on a scale Standard Deviation 0.96	—
Mean Change From Double-blind Baseline in Morning Stiffness Severity Double Blind Week 28- Tapering arm	0.2 units on a scale Standard Deviation 1.10	0.9 units on a scale Standard Deviation 1.69	—
Mean Change From Double-blind Baseline in Morning Stiffness Severity Double Blind Week 28- Withdrawal Arm	-0.2 units on a scale Standard Deviation 0.87	1.3 units on a scale Standard Deviation 2.75	—
Mean Change From Double-blind Baseline in Morning Stiffness Severity Double Blind Week 34- Tapering Arm	0.1 units on a scale Standard Deviation 0.85	1.3 units on a scale Standard Deviation 1.71	—
Mean Change From Double-blind Baseline in Morning Stiffness Severity Double Blind Week 34- Withdrawal Arm	-0.2 units on a scale Standard Deviation 1.08	0.0 units on a scale Standard Deviation 1.41	—
Mean Change From Double-blind Baseline in Morning Stiffness Severity Double Blind Week 40- Tapering Arm	0.1 units on a scale Standard Deviation 0.94	1.8 units on a scale Standard Deviation 2.52	—
Mean Change From Double-blind Baseline in Morning Stiffness Severity Double Blind Week 40- Withdrawal Arm	-0.4 units on a scale Standard Deviation 1.03	-1.0 units on a scale Standard Deviation 1.41	—
Mean Change From Double-blind Baseline in Morning Stiffness Severity Flare Week 0- Tapering Arm	—	1.6 units on a scale Standard Deviation 2.11	—
Mean Change From Double-blind Baseline in Morning Stiffness Severity Flare Week 0- Withdrawal Arm	—	0.9 units on a scale Standard Deviation 1.96	—
Mean Change From Double-blind Baseline in Morning Stiffness Severity Flare Week 4- Tapering Arm	—	0.8 units on a scale Standard Deviation 2.21	—
Mean Change From Double-blind Baseline in Morning Stiffness Severity Flare Week 4- Withdrawal Arm	—	0.6 units on a scale Standard Deviation 1.72	—
Mean Change From Double-blind Baseline in Morning Stiffness Severity Flare Week 10- Tapering Arm	—	0.6 units on a scale Standard Deviation 1.40	—
Mean Change From Double-blind Baseline in Morning Stiffness Severity Flare Week 10- Withdrawal Arm	—	0.6 units on a scale Standard Deviation 1.27	—
Mean Change From Double-blind Baseline in Morning Stiffness Severity Flare Week 16- Tapering Arm	—	0.6 units on a scale Standard Deviation 1.45	—
Mean Change From Double-blind Baseline in Morning Stiffness Severity Flare Week 16- Withdrawal Arm	—	-0.1 units on a scale Standard Deviation 1.13	—

SECONDARY outcome

Timeframe: From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16

Population: Double-blind Treated Subject population: participants who received at least 1 dose of study drug during the Double-blind period and had at least Double-blind Baseline data for this endpoint

Participants rated the severity of their sleep disturbance in the past week by placing a vertical mark on a line with a range of 0 (sleep is no problem) to 100 mm (sleep is a major problem). Negative values indicate improvement from baseline.

Outcome measures

Outcome measures
Measure	Non-Flared Participants n=76 Participants Participants who did not experience flare during the Double-blind Period	Flared Participants n=46 Participants Participants who experienced flare during the Double-blind Period	CDAI ≤ 2.8 Clinical Disease Activity Index (CDAI) score ≤ 2.8
Mean Change From Double-blind Baseline in Participant's Assessment of Sleep Disturbance Flare Week 10- Tapering Arm	—	0.2 units on a scale Standard Deviation 21.26	—
Mean Change From Double-blind Baseline in Participant's Assessment of Sleep Disturbance Double Blind Week 10- Tapering Arm	0.0 units on a scale Standard Deviation 8.99	2.1 units on a scale Standard Deviation 15.37	—
Mean Change From Double-blind Baseline in Participant's Assessment of Sleep Disturbance Double Blind Week 10- Withdrawal Arm	0.8 units on a scale Standard Deviation 1.54	-3.2 units on a scale Standard Deviation 29.39	—
Mean Change From Double-blind Baseline in Participant's Assessment of Sleep Disturbance Double Blind Week 16- Tapering Arm	1.7 units on a scale Standard Deviation 15.96	10.2 units on a scale Standard Deviation 19.12	—
Mean Change From Double-blind Baseline in Participant's Assessment of Sleep Disturbance Double Blind Week 16- Withdrawal Arm	1.1 units on a scale Standard Deviation 3.02	7.1 units on a scale Standard Deviation 22.42	—
Mean Change From Double-blind Baseline in Participant's Assessment of Sleep Disturbance Double Blind Week 22- Tapering Arm	-0.3 units on a scale Standard Deviation 10.91	8.2 units on a scale Standard Deviation 19.59	—
Mean Change From Double-blind Baseline in Participant's Assessment of Sleep Disturbance Double Blind Week 22- Withdrawal arm	3.5 units on a scale Standard Deviation 8.70	8.3 units on a scale Standard Deviation 31.35	—
Mean Change From Double-blind Baseline in Participant's Assessment of Sleep Disturbance Double Blind Week 28- Tapering arm	2.1 units on a scale Standard Deviation 12.67	1.8 units on a scale Standard Deviation 27.81	—
Mean Change From Double-blind Baseline in Participant's Assessment of Sleep Disturbance Double Blind Week 28- Withdrawal Arm	-1.0 units on a scale Standard Deviation 7.63	4.5 units on a scale Standard Deviation 19.82	—
Mean Change From Double-blind Baseline in Participant's Assessment of Sleep Disturbance Double Blind Week 34- Tapering Arm	-0.4 units on a scale Standard Deviation 11.48	5.6 units on a scale Standard Deviation 22.99	—
Mean Change From Double-blind Baseline in Participant's Assessment of Sleep Disturbance Double Blind Week 34- Withdrawal Arm	-0.4 units on a scale Standard Deviation 2.77	-0.5 units on a scale Standard Deviation 30.41	—
Mean Change From Double-blind Baseline in Participant's Assessment of Sleep Disturbance Double Blind Week 40- Tapering Arm	-0.2 units on a scale Standard Deviation 12.40	17.7 units on a scale Standard Deviation 34.04	—
Mean Change From Double-blind Baseline in Participant's Assessment of Sleep Disturbance Double Blind Week 40- Withdrawal Arm	-1.0 units on a scale Standard Deviation 4.43	-8.0 units on a scale Standard Deviation 15.56	—
Mean Change From Double-blind Baseline in Participant's Assessment of Sleep Disturbance Flare Week 0- Tapering Arm	—	18.9 units on a scale Standard Deviation 26.53	—
Mean Change From Double-blind Baseline in Participant's Assessment of Sleep Disturbance Flare Week 0- Withdrawal Arm	—	4.0 units on a scale Standard Deviation 14.61	—
Mean Change From Double-blind Baseline in Participant's Assessment of Sleep Disturbance Flare Week 4- Tapering Arm	—	4.9 units on a scale Standard Deviation 24.33	—
Mean Change From Double-blind Baseline in Participant's Assessment of Sleep Disturbance Flare Week 4- Withdrawal Arm	—	1.6 units on a scale Standard Deviation 10.05	—
Mean Change From Double-blind Baseline in Participant's Assessment of Sleep Disturbance Flare Week 10- Withdrawal Arm	—	3.9 units on a scale Standard Deviation 12.98	—
Mean Change From Double-blind Baseline in Participant's Assessment of Sleep Disturbance Flare Week 16- Tapering Arm	—	2.3 units on a scale Standard Deviation 20.17	—
Mean Change From Double-blind Baseline in Participant's Assessment of Sleep Disturbance Flare Week 16- Withdrawal Arm	—	-7.3 units on a scale Standard Deviation 14.14	—

SECONDARY outcome

Timeframe: At Weeks 4, 16, 28, and 40 and from Flare Week 0 to Flare Week 16

Population: Double-blind Treated Subject population: participants who received at least 1 dose of study drug during the Double-blind period and had at least Double-blind Baseline data for this endpoint

Participants completed the 14-item Treatment Satisfaction Questionnaire for Medication (TSQM; Version 1.4) to assess satisfaction with their current rheumatoid arthritis treatment over the previous 2-3 weeks or since the last time that they took the medication. The TSQM consists of fourteen items over four domains (effectiveness, side effects, convenience, and global satisfaction). The 14 questions are answered either with yes/no or by means of a five or seven stage scale (ranging from very unsatisfied to satisfied). TSQM Scale scores for each domain range from 0 to 100 and higher scores represent higher satisfaction. Negative values indicate worsening from baseline.

Outcome measures

Outcome measures
Measure	Non-Flared Participants n=74 Participants Participants who did not experience flare during the Double-blind Period	Flared Participants n=46 Participants Participants who experienced flare during the Double-blind Period	CDAI ≤ 2.8 Clinical Disease Activity Index (CDAI) score ≤ 2.8
Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Effectiveness Score Double Blind Week 16- Tapering Arm	0.2 units on a scale Standard Deviation 23.74	-8.3 units on a scale Standard Deviation 35.30	—
Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Effectiveness Score Double Blind Week 16- Withdrawal Arm	-13.6 units on a scale Standard Deviation 43.84	2.8 units on a scale Standard Deviation 39.51	—
Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Effectiveness Score Double Blind Week 28- Tapering arm	-3.8 units on a scale Standard Deviation 17.82	-10.1 units on a scale Standard Deviation 24.28	—
Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Effectiveness Score Double Blind Week 28- Withdrawal Arm	-17.2 units on a scale Standard Deviation 30.48	-5.6 units on a scale Standard Deviation 45.59	—
Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Effectiveness Score Double Blind Week 40- Tapering Arm	-4.4 units on a scale Standard Deviation 27.82	-15.2 units on a scale Standard Deviation 33.53	—
Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Effectiveness Score Double Blind Week 40- Withdrawal Arm	-16.2 units on a scale Standard Deviation 45.10	-19.4 units on a scale Standard Deviation 27.50	—
Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Effectiveness Score Flare Week 0- Tapering Arm	—	-10.9 units on a scale Standard Deviation 39.82	—
Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Effectiveness Score Flare Week 0- Withdrawal Arm	—	-9.5 units on a scale Standard Deviation 38.05	—
Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Effectiveness Score Flare Week 4- Tapering Arm	—	-17.3 units on a scale Standard Deviation 40.07	—
Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Effectiveness Score Flare Week 4- Withdrawal Arm	—	-6.5 units on a scale Standard Deviation 48.23	—
Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Effectiveness Score Flare Week 10- Tapering Arm	—	-10.7 units on a scale Standard Deviation 44.07	—
Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Effectiveness Score Flare Week 10- Withdrawal Arm	—	7.9 units on a scale Standard Deviation 34.23	—
Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Effectiveness Score Flare Week 16- Tapering Arm	—	-7.5 units on a scale Standard Deviation 25.49	—
Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Effectiveness Score Flare Week 16- Withdrawal Arm	—	-16.7 units on a scale Standard Deviation 39.67	—

SECONDARY outcome

Timeframe: At Weeks 4, 16, 28, and 40 and from Flare Week 0 to Flare Week 16

Population: Double-blind Treated Subject population: participants who received at least 1 dose of study drug during the Double-blind period and had at least Double-blind Baseline data for this endpoint

Participants completed the 14-item Treatment Satisfaction Questionnaire for Medication (TSQM; Version 1.4) to assess satisfaction with their current rheumatoid arthritis treatment over the previous 2-3 weeks or since the last time that they took the medication. The TSQM consists of fourteen items over four domains (effectiveness, side effects, convenience, and global satisfaction). The 14 questions are answered either with yes/no or by means of a five or seven stage scale (ranging from very unsatisfied to satisfied). TSQM Scale scores for each domain range from 0 to 100 and higher scores represent higher satisfaction. Negative values indicate worsening from baseline.

Outcome measures

Outcome measures
Measure	Non-Flared Participants n=74 Participants Participants who did not experience flare during the Double-blind Period	Flared Participants n=46 Participants Participants who experienced flare during the Double-blind Period	CDAI ≤ 2.8 Clinical Disease Activity Index (CDAI) score ≤ 2.8
Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Side Effects Score Flare Week 16- Withdrawal Arm	—	2.7 units on a scale Standard Deviation 7.09	—
Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Side Effects Score Double Blind Week 16- Tapering Arm	-0.5 units on a scale Standard Deviation 11.26	-8.0 units on a scale Standard Deviation 17.25	—
Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Side Effects Score Double Blind Week 16- Withdrawal Arm	2.8 units on a scale Standard Deviation 9.42	9.4 units on a scale Standard Deviation 20.04	—
Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Side Effects Score Double Blind Week 28- Tapering arm	1.1 units on a scale Standard Deviation 7.44	-2.7 units on a scale Standard Deviation 12.28	—
Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Side Effects Score Double Blind Week 28- Withdrawal Arm	2.8 units on a scale Standard Deviation 9.42	14.1 units on a scale Standard Deviation 28.13	—
Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Side Effects Score Double Blind Week 40- Tapering Arm	1.1 units on a scale Standard Deviation 11.61	-2.3 units on a scale Standard Deviation 14.86	—
Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Side Effects Score Double Blind Week 40- Withdrawal Arm	2.8 units on a scale Standard Deviation 9.42	28.1 units on a scale Standard Deviation 39.77	—
Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Side Effects Score Flare Week 0- Tapering Arm	—	-5.1 units on a scale Standard Deviation 15.96	—
Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Side Effects Score Flare Week 0- Withdrawal Arm	—	2.7 units on a scale Standard Deviation 7.09	—
Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Side Effects Score Flare Week 4- Tapering Arm	—	-5.0 units on a scale Standard Deviation 19.52	—
Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Side Effects Score Flare Week 4- Withdrawal Arm	—	3.1 units on a scale Standard Deviation 7.65	—
Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Side Effects Score Flare Week 10- Tapering Arm	—	-3.7 units on a scale Standard Deviation 13.90	—
Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Side Effects Score Flare Week 10- Withdrawal Arm	—	2.7 units on a scale Standard Deviation 7.09	—
Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Side Effects Score Flare Week 16- Tapering Arm	—	-2.0 units on a scale Standard Deviation 6.60	—

SECONDARY outcome

Timeframe: At Weeks 4, 16, 28, and 40 and from Flare Week 0 to Flare Week 16

Population: Double-blind Treated Subject population: participants who received at least 1 dose of study drug during the Double-blind period and had at least Double-blind Baseline data for this endpoint

Participants completed the 14-item Treatment Satisfaction Questionnaire for Medication (TSQM; Version 1.4) to assess satisfaction with their current rheumatoid arthritis treatment over the previous 2-3 weeks or since the last time that they took the medication. The TSQM consists of fourteen items over four domains (effectiveness, side effects, convenience, and global satisfaction). The 14 questions are answered either with yes/no or by means of a five or seven stage scale (ranging from very unsatisfied to satisfied). TSQM Scale scores for each domain range from 0 to 100 and higher scores represent higher satisfaction. Negative values indicate worsening from baseline.

Outcome measures

Outcome measures
Measure	Non-Flared Participants n=74 Participants Participants who did not experience flare during the Double-blind Period	Flared Participants n=46 Participants Participants who experienced flare during the Double-blind Period	CDAI ≤ 2.8 Clinical Disease Activity Index (CDAI) score ≤ 2.8
Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Convenience Score Double Blind Week 16- Tapering Arm	0.8 units on a scale Standard Deviation 13.45	-0.2 units on a scale Standard Deviation 16.96	—
Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Convenience Score Double Blind Week 16- Withdrawal Arm	4.0 units on a scale Standard Deviation 10.86	-4.9 units on a scale Standard Deviation 19.57	—
Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Convenience Score Double Blind Week 28- Tapering arm	-1.0 units on a scale Standard Deviation 15.47	0.0 units on a scale Standard Deviation 18.70	—
Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Convenience Score Double Blind Week 28- Withdrawal Arm	-3.5 units on a scale Standard Deviation 13.21	-4.2 units on a scale Standard Deviation 12.32	—
Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Convenience Score Double Blind Week 40- Tapering Arm	-0.1 units on a scale Standard Deviation 16.50	-4.0 units on a scale Standard Deviation 9.65	—
Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Convenience Score Double Blind Week 40- Withdrawal Arm	2.5 units on a scale Standard Deviation 18.32	-16.7 units on a scale Standard Deviation 23.57	—
Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Convenience Score Flare Week 0- Tapering Arm	—	4.2 units on a scale Standard Deviation 12.53	—
Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Convenience Score Flare Week 0- Withdrawal Arm	—	-7.1 units on a scale Standard Deviation 14.60	—
Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Convenience Score Flare Week 4- Tapering Arm	—	4.4 units on a scale Standard Deviation 19.84	—
Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Convenience Score Flare Week 4- Withdrawal Arm	—	5.6 units on a scale Standard Deviation 18.92	—
Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Convenience Score Flare Week 10- Tapering Arm	—	1.2 units on a scale Standard Deviation 10.60	—
Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Convenience Score Flare Week 10- Withdrawal Arm	—	0.8 units on a scale Standard Deviation 16.49	—
Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Convenience Score Flare Week 16- Tapering Arm	—	1.6 units on a scale Standard Deviation 19.65	—
Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Convenience Score Flare Week 16- Withdrawal Arm	—	0.8 units on a scale Standard Deviation 20.89	—

SECONDARY outcome

Timeframe: At Weeks 4, 16, 28, and 40 and from Flare Week 0 to Flare Week 16

Population: Double-blind Treated Subject population: participants who received at least 1 dose of study drug during the Double-blind period and had at least Double-blind Baseline data for this endpoint

Participants completed the 14-item Treatment Satisfaction Questionnaire for Medication (TSQM; Version 1.4) to assess satisfaction with their current rheumatoid arthritis treatment over the previous 2-3 weeks or since the last time that they took the medication. The TSQM consists of fourteen items over four domains (effectiveness, side effects, convenience, and global satisfaction). The 14 questions are answered either with yes/no or by means of a five or seven stage scale (ranging from very unsatisfied to satisfied). TSQM Scale scores for each domain range from 0 to 100 and higher scores represent higher satisfaction. Negative values indicate worsening from baseline.

Outcome measures

Outcome measures
Measure	Non-Flared Participants n=74 Participants Participants who did not experience flare during the Double-blind Period	Flared Participants n=46 Participants Participants who experienced flare during the Double-blind Period	CDAI ≤ 2.8 Clinical Disease Activity Index (CDAI) score ≤ 2.8
Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Global Satisfaction Score Double Blind Week 16- Tapering Arm	-3.4 units on a scale Standard Deviation 17.91	-11.6 units on a scale Standard Deviation 24.99	—
Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Global Satisfaction Score Double Blind Week 16- Withdrawal Arm	0.6 units on a scale Standard Deviation 22.69	-2.7 units on a scale Standard Deviation 15.24	—
Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Global Satisfaction Score Double Blind Week 28- Tapering arm	-5.7 units on a scale Standard Deviation 14.97	-2.2 units on a scale Standard Deviation 12.70	—
Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Global Satisfaction Score Double Blind Week 28- Withdrawal Arm	-4.5 units on a scale Standard Deviation 25.81	5.4 units on a scale Standard Deviation 15.84	—
Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Global Satisfaction Score Double Blind Week 40- Tapering Arm	-2.6 units on a scale Standard Deviation 15.10	-3.2 units on a scale Standard Deviation 13.31	—
Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Global Satisfaction Score Double Blind Week 40- Withdrawal Arm	-3.2 units on a scale Standard Deviation 21.98	0.0 units on a scale Standard Deviation 10.10	—
Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Global Satisfaction Score Flare Week 0- Tapering Arm	—	-11.7 units on a scale Standard Deviation 27.58	—
Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Global Satisfaction Score Flare Week 0- Withdrawal Arm	—	-9.2 units on a scale Standard Deviation 25.66	—
Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Global Satisfaction Score Flare Week 4- Tapering Arm	—	-3.1 units on a scale Standard Deviation 20.32	—
Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Global Satisfaction Score Flare Week 4- Withdrawal Arm	—	-1.2 units on a scale Standard Deviation 24.08	—
Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Global Satisfaction Score Flare Week 10- Tapering Arm	—	-0.8 units on a scale Standard Deviation 13.77	—
Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Global Satisfaction Score Flare Week 10- Withdrawal Arm	—	-2.0 units on a scale Standard Deviation 18.77	—
Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Global Satisfaction Score Flare Week 16- Tapering Arm	—	-6.6 units on a scale Standard Deviation 24.20	—
Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Global Satisfaction Score Flare Week 16- Withdrawal Arm	—	-8.2 units on a scale Standard Deviation 16.72	—

SECONDARY outcome

Timeframe: At Weeks 4, 28, and 40 and Flare Weeks 0, 10, and 16

Population: Double-blind Treated Subject population: participants who received at least 1 dose of study drug during the Double-blind period and had at least Double-blind Baseline data for this endpoint

The Work Productivity and Activity Impairment (WPAI) questionnaire for general health is a validated tool in rheumatoid arthritis consisting of 6 questions, based on participant recall of the previous 7 days. WPAI assesses work time missed due to illness (absenteeism), impairment at work due to health (presenteeism), overall work impairment due to health (an aggregate measure of both absenteeism and presenteeism), and total non-occupational activity impairment due to health. WPAI scores are expressed as impairment percentages, with higher scores indicating worse outcomes. A negative change from baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Non-Flared Participants n=75 Participants Participants who did not experience flare during the Double-blind Period	Flared Participants n=46 Participants Participants who experienced flare during the Double-blind Period	CDAI ≤ 2.8 Clinical Disease Activity Index (CDAI) score ≤ 2.8
Mean Change From Double-blind Baseline in Work Productivity and Activity Impairment (WPAI) Overall Work Impairment and Activity Impairment Scores Overall Work Impairment at Week 28- Withdrawal Arm	0.6 percent impairment Standard Deviation 8.12	0.0 percent impairment	—
Mean Change From Double-blind Baseline in Work Productivity and Activity Impairment (WPAI) Overall Work Impairment and Activity Impairment Scores Activity Impairment at Week 28- Tapering arm	2.8 percent impairment Standard Deviation 13.43	5.0 percent impairment Standard Deviation 19.51	—
Mean Change From Double-blind Baseline in Work Productivity and Activity Impairment (WPAI) Overall Work Impairment and Activity Impairment Scores Overall Work Impairment at Week 28- Tapering Arm	3.5 percent impairment Standard Deviation 10.68	15.0 percent impairment Standard Deviation 21.21	—
Mean Change From Double-blind Baseline in Work Productivity and Activity Impairment (WPAI) Overall Work Impairment and Activity Impairment Scores Activity Impairment at Week 28- Withdrawal Arm	-0.9 percent impairment Standard Deviation 7.01	10.0 percent impairment Standard Deviation 17.32	—
Mean Change From Double-blind Baseline in Work Productivity and Activity Impairment (WPAI) Overall Work Impairment and Activity Impairment Scores Overall Work Impairment at Week 40- Tapering Arm	3.4 percent impairment Standard Deviation 18.78	—	—
Mean Change From Double-blind Baseline in Work Productivity and Activity Impairment (WPAI) Overall Work Impairment and Activity Impairment Scores Overall Work Impairment at Week 40- Withdrawal Arm	0.6 percent impairment Standard Deviation 8.12	—	—
Mean Change From Double-blind Baseline in Work Productivity and Activity Impairment (WPAI) Overall Work Impairment and Activity Impairment Scores Activity Impairment at Week 40- Tapering arm	0.5 percent impairment Standard Deviation 13.59	15.7 percent impairment Standard Deviation 9.76	—
Mean Change From Double-blind Baseline in Work Productivity and Activity Impairment (WPAI) Overall Work Impairment and Activity Impairment Scores Activity Impairment at Week 40- Withdrawal Arm	0.0 percent impairment Standard Deviation 6.32	20.0 percent impairment	—
Mean Change From Double-blind Baseline in Work Productivity and Activity Impairment (WPAI) Overall Work Impairment and Activity Impairment Scores Overall Work Impairment Flare Wk 0- Tapering Arm	—	14.0 percent impairment Standard Deviation 27.02	—
Mean Change From Double-blind Baseline in Work Productivity and Activity Impairment (WPAI) Overall Work Impairment and Activity Impairment Scores Overall Work Impairment Flare Wk 0- Withdrawal Arm	—	5.0 percent impairment Standard Deviation 7.07	—
Mean Change From Double-blind Baseline in Work Productivity and Activity Impairment (WPAI) Overall Work Impairment and Activity Impairment Scores Activity Impairment Flare Week 0- Tapering Arm	—	25.9 percent impairment Standard Deviation 31.57	—
Mean Change From Double-blind Baseline in Work Productivity and Activity Impairment (WPAI) Overall Work Impairment and Activity Impairment Scores Activity Impairment Flare Week 0- Withdrawal Arm	—	8.0 percent impairment Standard Deviation 25.88	—
Mean Change From Double-blind Baseline in Work Productivity and Activity Impairment (WPAI) Overall Work Impairment and Activity Impairment Scores Overall Work Impairment Flare Wk 10- Tapering Arm	—	-0.2 percent impairment Standard Deviation 8.78	—
Mean Change From Double-blind Baseline in Work Productivity and Activity Impairment (WPAI) Overall Work Impairment and Activity Impairment Scores Overall Work Impairment Flare W 10- Withdrawal Arm	—	5.0 percent impairment Standard Deviation 7.07	—
Mean Change From Double-blind Baseline in Work Productivity and Activity Impairment (WPAI) Overall Work Impairment and Activity Impairment Scores Activity Impairment Flare Wk 10- Tapering Arm	—	6.5 percent impairment Standard Deviation 15.48	—
Mean Change From Double-blind Baseline in Work Productivity and Activity Impairment (WPAI) Overall Work Impairment and Activity Impairment Scores Activity Impairment Flare W 10- Withdrawal Arm	—	12.9 percent impairment Standard Deviation 13.80	—
Mean Change From Double-blind Baseline in Work Productivity and Activity Impairment (WPAI) Overall Work Impairment and Activity Impairment Scores Overall Work Impairment Flare Wk 16- Tapering Arm	—	10.0 percent impairment Standard Deviation 14.82	—
Mean Change From Double-blind Baseline in Work Productivity and Activity Impairment (WPAI) Overall Work Impairment and Activity Impairment Scores Overall Work Impairment Flare W 16- Withdrawal Arm	—	10.0 percent impairment Standard Deviation 10.00	—
Mean Change From Double-blind Baseline in Work Productivity and Activity Impairment (WPAI) Overall Work Impairment and Activity Impairment Scores Activity Impairment Flare Wk 16- Tapering Arm	—	11.0 percent impairment Standard Deviation 17.39	—
Mean Change From Double-blind Baseline in Work Productivity and Activity Impairment (WPAI) Overall Work Impairment and Activity Impairment Scores Activity Impairment Flare Wk 16- Withdrawal Arm	—	8.8 percent impairment Standard Deviation 11.26	—

SECONDARY outcome

Timeframe: At Weeks 4, 28, and 40 and from Flare Week 0 to Flare Week 16

Population: Double-blind Treated Subject population: participants who received at least 1 dose of study drug during the Double-blind period and had at least Double-blind Baseline data for this endpoint

The SF-36v2 is a non-disease specific Health Related Quality of Life (HRQoL) instrument. The SF-36v2 comprises 36 total items (questions) targeting a subject's functional health and well-being in 8 domains (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional and mental health) with a recall period of four weeks. Domain scores are aggregated into a Physical Component Summary (PCS) score and a Mental Component Summary (MCS) score. SF-36v2 scores for each domain and PCS/MCS range from 0-100: higher scores indicate a better state of health and a decrease from baseline represents worsening.

Outcome measures

Outcome measures
Measure	Non-Flared Participants n=74 Participants Participants who did not experience flare during the Double-blind Period	Flared Participants n=45 Participants Participants who experienced flare during the Double-blind Period	CDAI ≤ 2.8 Clinical Disease Activity Index (CDAI) score ≤ 2.8
Mean Change From Double-blind Baseline in Short-Form 36 Version 2 Health Survey (SF-36v2) Physical Component Summary (PCS) Score Double Blind Week 28- Tapering arm	-1.1 units on a scale Standard Deviation 4.18	-2.9 units on a scale Standard Deviation 7.53	—
Mean Change From Double-blind Baseline in Short-Form 36 Version 2 Health Survey (SF-36v2) Physical Component Summary (PCS) Score Double Blind Week 28- Withdrawal Arm	-2.4 units on a scale Standard Deviation 3.97	-1.9 units on a scale Standard Deviation 7.39	—
Mean Change From Double-blind Baseline in Short-Form 36 Version 2 Health Survey (SF-36v2) Physical Component Summary (PCS) Score Double Blind Week 40- Tapering Arm	-0.4 units on a scale Standard Deviation 5.53	-5.5 units on a scale Standard Deviation 6.42	—
Mean Change From Double-blind Baseline in Short-Form 36 Version 2 Health Survey (SF-36v2) Physical Component Summary (PCS) Score Double Blind Week 40- Withdrawal Arm	-2.1 units on a scale Standard Deviation 5.22	-1.6 units on a scale	—
Mean Change From Double-blind Baseline in Short-Form 36 Version 2 Health Survey (SF-36v2) Physical Component Summary (PCS) Score Flare Week 0- Tapering Arm	—	-10.8 units on a scale Standard Deviation 10.85	—
Mean Change From Double-blind Baseline in Short-Form 36 Version 2 Health Survey (SF-36v2) Physical Component Summary (PCS) Score Flare Week 0- Withdrawal Arm	—	-2.4 units on a scale Standard Deviation 10.81	—
Mean Change From Double-blind Baseline in Short-Form 36 Version 2 Health Survey (SF-36v2) Physical Component Summary (PCS) Score Flare Week 4- Tapering Arm	—	-5.2 units on a scale Standard Deviation 8.37	—
Mean Change From Double-blind Baseline in Short-Form 36 Version 2 Health Survey (SF-36v2) Physical Component Summary (PCS) Score Flare Week 4- Withdrawal Arm	—	-8.0 units on a scale Standard Deviation 7.35	—
Mean Change From Double-blind Baseline in Short-Form 36 Version 2 Health Survey (SF-36v2) Physical Component Summary (PCS) Score Flare Week 10- Tapering Arm	—	-4.0 units on a scale Standard Deviation 7.22	—
Mean Change From Double-blind Baseline in Short-Form 36 Version 2 Health Survey (SF-36v2) Physical Component Summary (PCS) Score Flare Week 10- Withdrawal Arm	—	-4.0 units on a scale Standard Deviation 4.57	—
Mean Change From Double-blind Baseline in Short-Form 36 Version 2 Health Survey (SF-36v2) Physical Component Summary (PCS) Score Flare Week 16- Tapering Arm	—	-3.8 units on a scale Standard Deviation 7.38	—
Mean Change From Double-blind Baseline in Short-Form 36 Version 2 Health Survey (SF-36v2) Physical Component Summary (PCS) Score Flare Week 16- Withdrawal Arm	—	-2.5 units on a scale Standard Deviation 2.80	—

SECONDARY outcome

Timeframe: At Weeks 4, 28, and 40 and from Flare Week 0 to Flare Week 16

Population: Double-blind Treated Subject population: participants who received at least 1 dose of study drug during the Double-blind period and had at least Double-blind Baseline data for this endpoint

The SF-36v2 is a non-disease specific Health Related Quality of Life (HRQoL) instrument. The SF-36v2 comprises 36 total items (questions) targeting a subject's functional health and well-being in 8 domains (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional and mental health) with a recall period of four weeks. Domain scores are aggregated into a Physical Component Summary (PCS) score and a Mental Component Summary (MCS) score. SF-36v2 scores for each domain and PCS/MCS range from 0-100: higher scores indicate a better state of health and a decrease from baseline represents worsening.

Outcome measures

Outcome measures
Measure	Non-Flared Participants n=74 Participants Participants who did not experience flare during the Double-blind Period	Flared Participants n=45 Participants Participants who experienced flare during the Double-blind Period	CDAI ≤ 2.8 Clinical Disease Activity Index (CDAI) score ≤ 2.8
Mean Change From Double-blind Baseline in Short-Form 36 Version 2 Health Survey (SF-36v2) Mental Component Summary (MCS) Score Double Blind Week 28- Tapering arm	-0.8 units on a scale Standard Deviation 6.02	-5.5 units on a scale Standard Deviation 11.31	—
Mean Change From Double-blind Baseline in Short-Form 36 Version 2 Health Survey (SF-36v2) Mental Component Summary (MCS) Score Double Blind Week 28- Withdrawal Arm	-0.1 units on a scale Standard Deviation 7.20	-5.2 units on a scale Standard Deviation 5.90	—
Mean Change From Double-blind Baseline in Short-Form 36 Version 2 Health Survey (SF-36v2) Mental Component Summary (MCS) Score Double Blind Week 40- Tapering Arm	-0.8 units on a scale Standard Deviation 5.89	-3.5 units on a scale Standard Deviation 11.14	—
Mean Change From Double-blind Baseline in Short-Form 36 Version 2 Health Survey (SF-36v2) Mental Component Summary (MCS) Score Double Blind Week 40- Withdrawal Arm	-0.4 units on a scale Standard Deviation 6.71	-8.5 units on a scale	—
Mean Change From Double-blind Baseline in Short-Form 36 Version 2 Health Survey (SF-36v2) Mental Component Summary (MCS) Score Flare Week 0- Tapering Arm	—	-4.1 units on a scale Standard Deviation 11.43	—
Mean Change From Double-blind Baseline in Short-Form 36 Version 2 Health Survey (SF-36v2) Mental Component Summary (MCS) Score Flare Week 0- Withdrawal Arm	—	0.4 units on a scale Standard Deviation 4.59	—
Mean Change From Double-blind Baseline in Short-Form 36 Version 2 Health Survey (SF-36v2) Mental Component Summary (MCS) Score Flare Week 4- Tapering Arm	—	-2.0 units on a scale Standard Deviation 5.95	—
Mean Change From Double-blind Baseline in Short-Form 36 Version 2 Health Survey (SF-36v2) Mental Component Summary (MCS) Score Flare Week 4- Withdrawal Arm	—	-0.5 units on a scale Standard Deviation 2.51	—
Mean Change From Double-blind Baseline in Short-Form 36 Version 2 Health Survey (SF-36v2) Mental Component Summary (MCS) Score Flare Week 10- Tapering Arm	—	-1.1 units on a scale Standard Deviation 10.14	—
Mean Change From Double-blind Baseline in Short-Form 36 Version 2 Health Survey (SF-36v2) Mental Component Summary (MCS) Score Flare Week 10- Withdrawal Arm	—	-0.4 units on a scale Standard Deviation 3.06	—
Mean Change From Double-blind Baseline in Short-Form 36 Version 2 Health Survey (SF-36v2) Mental Component Summary (MCS) Score Flare Week 16- Tapering Arm	—	-4.0 units on a scale Standard Deviation 11.01	—
Mean Change From Double-blind Baseline in Short-Form 36 Version 2 Health Survey (SF-36v2) Mental Component Summary (MCS) Score Flare Week 16- Withdrawal Arm	—	0.1 units on a scale Standard Deviation 2.55	—

SECONDARY outcome

Timeframe: At Weeks 4, 16, 28, and 40 and from Flare Week 0 to Flare Week 16

Population: Double-blind Treated Subject population: participants who received at least 1 dose of study drug during the Double-blind period and had at least Double-blind Baseline data for this endpoint

The FACIT-Fatigue questionnaire is a participant questionnaire that consists of 13 questions designed to measure the degree of fatigue experienced by participants in the previous 7 days. Participants respond to the questions on a scale from 'not at all' (0) to 'very much' (4). The scale score is computed by summing the item scores, after reversing those items that are worded in the negative direction. The FACIT-Fatigue subscale score ranges from 0 to 52, where higher scores represent less fatigue. A negative change from baseline indicates worsening.

Outcome measures

Outcome measures
Measure	Non-Flared Participants n=74 Participants Participants who did not experience flare during the Double-blind Period	Flared Participants n=46 Participants Participants who experienced flare during the Double-blind Period	CDAI ≤ 2.8 Clinical Disease Activity Index (CDAI) score ≤ 2.8
Mean Change From Double-blind Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale Double Blind Week 16- Tapering Arm	-1.5 units on a scale Standard Deviation 5.42	-6.0 units on a scale Standard Deviation 9.80	—
Mean Change From Double-blind Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale Double Blind Week 16- Withdrawal Arm	-1.9 units on a scale Standard Deviation 3.27	-2.3 units on a scale Standard Deviation 3.39	—
Mean Change From Double-blind Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale Double Blind Week 28- Tapering arm	-1.6 units on a scale Standard Deviation 5.60	-3.5 units on a scale Standard Deviation 7.58	—
Mean Change From Double-blind Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale Double Blind Week 28- Withdrawal Arm	-2.2 units on a scale Standard Deviation 4.67	-4.3 units on a scale Standard Deviation 7.23	—
Mean Change From Double-blind Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale Double Blind Week 40- Tapering Arm	-0.4 units on a scale Standard Deviation 4.00	-6.4 units on a scale Standard Deviation 8.44	—
Mean Change From Double-blind Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale Flare Week 0- Withdrawal Arm	—	-3.6 units on a scale Standard Deviation 4.75	—
Mean Change From Double-blind Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale Double Blind Week 40- Withdrawal Arm	-1.5 units on a scale Standard Deviation 4.78	-2.5 units on a scale Standard Deviation 6.36	—
Mean Change From Double-blind Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale Flare Week 0- Tapering Arm	—	-7.4 units on a scale Standard Deviation 11.17	—
Mean Change From Double-blind Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale Flare Week 4- Tapering Arm	—	-3.8 units on a scale Standard Deviation 9.19	—
Mean Change From Double-blind Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale Flare Week 4- Withdrawal Arm	—	-4.7 units on a scale Standard Deviation 5.43	—
Mean Change From Double-blind Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale Flare Week 10- Tapering Arm	—	-3.9 units on a scale Standard Deviation 8.44	—
Mean Change From Double-blind Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale Flare Week 10- Withdrawal Arm	—	-2.4 units on a scale Standard Deviation 4.47	—
Mean Change From Double-blind Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale Flare Week 16- Tapering Arm	—	-4.5 units on a scale Standard Deviation 9.01	—
Mean Change From Double-blind Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale Flare Week 16- Withdrawal Arm	—	-1.7 units on a scale Standard Deviation 1.89	—

SECONDARY outcome

Timeframe: From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16

Population: Double-blind Treated Subject population: participants who received at least 1 dose of study drug during the Double-blind period and had at least Double-blind Baseline data for this endpoint

C-Reactive Protein (CRP; mg/L) was measured from blood samples as a marker for inflammation. Higher levels are indicative of more inflammation. Negative values indicate improvement from baseline.

Outcome measures

Outcome measures
Measure	Non-Flared Participants n=76 Participants Participants who did not experience flare during the Double-blind Period	Flared Participants n=46 Participants Participants who experienced flare during the Double-blind Period	CDAI ≤ 2.8 Clinical Disease Activity Index (CDAI) score ≤ 2.8
Mean Change From Double-blind Baseline in Serum Levels of C-reactive Protein (CRP) Double Blind Week 10- Tapering Arm	1.7 mg/L Standard Deviation 12.92	-7.9 mg/L Standard Deviation 48.87	—
Mean Change From Double-blind Baseline in Serum Levels of C-reactive Protein (CRP) Double Blind Week 10- Withdrawal Arm	-0.6 mg/L Standard Deviation 2.53	-0.2 mg/L Standard Deviation 3.55	—
Mean Change From Double-blind Baseline in Serum Levels of C-reactive Protein (CRP) Double Blind Week 16- Tapering Arm	-0.4 mg/L Standard Deviation 4.26	-7.4 mg/L Standard Deviation 49.77	—
Mean Change From Double-blind Baseline in Serum Levels of C-reactive Protein (CRP) Double Blind Week 16- Withdrawal Arm	-0.1 mg/L Standard Deviation 3.67	6.6 mg/L Standard Deviation 12.26	—
Mean Change From Double-blind Baseline in Serum Levels of C-reactive Protein (CRP) Double Blind Week 22- Tapering Arm	-0.0 mg/L Standard Deviation 5.43	3.6 mg/L Standard Deviation 9.69	—
Mean Change From Double-blind Baseline in Serum Levels of C-reactive Protein (CRP) Double Blind Week 22- Withdrawal arm	-0.9 mg/L Standard Deviation 3.38	0.6 mg/L Standard Deviation 0.37	—
Mean Change From Double-blind Baseline in Serum Levels of C-reactive Protein (CRP) Double Blind Week 28- Tapering arm	-0.4 mg/L Standard Deviation 4.65	0.5 mg/L Standard Deviation 3.85	—
Mean Change From Double-blind Baseline in Serum Levels of C-reactive Protein (CRP) Double Blind Week 28- Withdrawal Arm	2.5 mg/L Standard Deviation 11.60	1.1 mg/L Standard Deviation 1.34	—
Mean Change From Double-blind Baseline in Serum Levels of C-reactive Protein (CRP) Double Blind Week 34- Tapering Arm	-0.4 mg/L Standard Deviation 4.41	3.2 mg/L Standard Deviation 10.13	—
Mean Change From Double-blind Baseline in Serum Levels of C-reactive Protein (CRP) Double Blind Week 34- Withdrawal Arm	0.3 mg/L Standard Deviation 5.98	1.8 mg/L Standard Deviation 1.89	—
Mean Change From Double-blind Baseline in Serum Levels of C-reactive Protein (CRP) Double Blind Week 40- Tapering Arm	-0.3 mg/L Standard Deviation 4.18	1.0 mg/L Standard Deviation 5.69	—
Mean Change From Double-blind Baseline in Serum Levels of C-reactive Protein (CRP) Double Blind Week 40- Withdrawal Arm	-0.1 mg/L Standard Deviation 3.43	8.3 mg/L Standard Deviation 11.60	—
Mean Change From Double-blind Baseline in Serum Levels of C-reactive Protein (CRP) Flare Week 0- Tapering Arm	—	-7.4 mg/L Standard Deviation 54.12	—
Mean Change From Double-blind Baseline in Serum Levels of C-reactive Protein (CRP) Flare Week 0- Withdrawal Arm	—	5.4 mg/L Standard Deviation 12.67	—
Mean Change From Double-blind Baseline in Serum Levels of C-reactive Protein (CRP) Flare Week 4- Tapering Arm	—	-8.5 mg/L Standard Deviation 55.47	—
Mean Change From Double-blind Baseline in Serum Levels of C-reactive Protein (CRP) Flare Week 4- Withdrawal Arm	—	-1.3 mg/L Standard Deviation 4.01	—
Mean Change From Double-blind Baseline in Serum Levels of C-reactive Protein (CRP) Flare Week 10- Tapering Arm	—	-9.5 mg/L Standard Deviation 55.61	—
Mean Change From Double-blind Baseline in Serum Levels of C-reactive Protein (CRP) Flare Week 10- Withdrawal Arm	—	-0.6 mg/L Standard Deviation 0.97	—
Mean Change From Double-blind Baseline in Serum Levels of C-reactive Protein (CRP) Flare Week 16- Tapering Arm	—	-9.1 mg/L Standard Deviation 53.70	—
Mean Change From Double-blind Baseline in Serum Levels of C-reactive Protein (CRP) Flare Week 16- Withdrawal Arm	—	-0.8 mg/L Standard Deviation 2.74	—

SECONDARY outcome

Timeframe: From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16

Population: Double-blind Treated Subject population: participants who received at least 1 dose of study drug during the Double-blind period and had at least Double-blind Baseline data for this endpoint

Erythrocyte sedimentation rate (ESR; mm/hour) indirectly measures how much inflammation is in the body. A higher ESR is indicative of increased inflammation. Negative values indicate improvement from baseline.

Outcome measures

Outcome measures
Measure	Non-Flared Participants n=76 Participants Participants who did not experience flare during the Double-blind Period	Flared Participants n=46 Participants Participants who experienced flare during the Double-blind Period	CDAI ≤ 2.8 Clinical Disease Activity Index (CDAI) score ≤ 2.8
Mean Change From Double-blind Baseline in Serum Levels of Erythrocyte Sedimentation Rate (ESR) Double Blind Week 10- Tapering Arm	0.7 mm/hour Standard Deviation 5.22	4.1 mm/hour Standard Deviation 11.25	—
Mean Change From Double-blind Baseline in Serum Levels of Erythrocyte Sedimentation Rate (ESR) Double Blind Week 10- Withdrawal Arm	-1.5 mm/hour Standard Deviation 5.43	0.9 mm/hour Standard Deviation 9.24	—
Mean Change From Double-blind Baseline in Serum Levels of Erythrocyte Sedimentation Rate (ESR) Double Blind Week 16- Tapering Arm	0.5 mm/hour Standard Deviation 5.82	4.6 mm/hour Standard Deviation 10.73	—
Mean Change From Double-blind Baseline in Serum Levels of Erythrocyte Sedimentation Rate (ESR) Double Blind Week 16- Withdrawal Arm	-0.3 mm/hour Standard Deviation 5.31	5.2 mm/hour Standard Deviation 15.23	—
Mean Change From Double-blind Baseline in Serum Levels of Erythrocyte Sedimentation Rate (ESR) Double Blind Week 22- Tapering Arm	-0.5 mm/hour Standard Deviation 7.38	3.5 mm/hour Standard Deviation 10.73	—
Mean Change From Double-blind Baseline in Serum Levels of Erythrocyte Sedimentation Rate (ESR) Double Blind Week 22- Withdrawal arm	-0.3 mm/hour Standard Deviation 4.22	2.8 mm/hour Standard Deviation 9.22	—
Mean Change From Double-blind Baseline in Serum Levels of Erythrocyte Sedimentation Rate (ESR) Double Blind Week 28- Tapering arm	0.4 mm/hour Standard Deviation 6.93	3.4 mm/hour Standard Deviation 8.18	—
Mean Change From Double-blind Baseline in Serum Levels of Erythrocyte Sedimentation Rate (ESR) Double Blind Week 28- Withdrawal Arm	1.0 mm/hour Standard Deviation 5.04	6.0 mm/hour Standard Deviation 10.10	—
Mean Change From Double-blind Baseline in Serum Levels of Erythrocyte Sedimentation Rate (ESR) Double Blind Week 34- Tapering Arm	0.3 mm/hour Standard Deviation 7.57	4.8 mm/hour Standard Deviation 7.28	—
Mean Change From Double-blind Baseline in Serum Levels of Erythrocyte Sedimentation Rate (ESR) Double Blind Week 34- Withdrawal Arm	-0.5 mm/hour Standard Deviation 5.94	-5.0 mm/hour Standard Deviation 1.41	—
Mean Change From Double-blind Baseline in Serum Levels of Erythrocyte Sedimentation Rate (ESR) Double Blind Week 40- Tapering Arm	1.4 mm/hour Standard Deviation 7.19	10.2 mm/hour Standard Deviation 13.22	—
Mean Change From Double-blind Baseline in Serum Levels of Erythrocyte Sedimentation Rate (ESR) Flare Week 0- Tapering Arm	—	10.4 mm/hour Standard Deviation 12.50	—
Mean Change From Double-blind Baseline in Serum Levels of Erythrocyte Sedimentation Rate (ESR) Flare Week 0- Withdrawal Arm	—	13.0 mm/hour Standard Deviation 11.90	—
Mean Change From Double-blind Baseline in Serum Levels of Erythrocyte Sedimentation Rate (ESR) Flare Week 4- Tapering Arm	—	7.2 mm/hour Standard Deviation 9.82	—
Mean Change From Double-blind Baseline in Serum Levels of Erythrocyte Sedimentation Rate (ESR) Flare Week 4- Withdrawal Arm	—	8.5 mm/hour Standard Deviation 9.52	—
Mean Change From Double-blind Baseline in Serum Levels of Erythrocyte Sedimentation Rate (ESR) Flare Week 10- Tapering Arm	—	5.8 mm/hour Standard Deviation 10.16	—
Mean Change From Double-blind Baseline in Serum Levels of Erythrocyte Sedimentation Rate (ESR) Flare Week 10- Withdrawal Arm	—	4.4 mm/hour Standard Deviation 6.91	—
Mean Change From Double-blind Baseline in Serum Levels of Erythrocyte Sedimentation Rate (ESR) Flare Week 16- Tapering Arm	—	8.0 mm/hour Standard Deviation 10.95	—
Mean Change From Double-blind Baseline in Serum Levels of Erythrocyte Sedimentation Rate (ESR) Flare Week 16- Withdrawal Arm	—	7.0 mm/hour Standard Deviation 14.40	—
Mean Change From Double-blind Baseline in Serum Levels of Erythrocyte Sedimentation Rate (ESR) Double Blind Week 40- Withdrawal Arm	4.7 mm/hour Standard Deviation 8.89	-2.0 mm/hour Standard Deviation 5.66	—

Adverse Events

Adalimumab 40 mg Eow

Serious events: 4 serious events

Other events: 11 other events

Deaths: 0 deaths

Adalimumab Tapering

Serious events: 1 serious events

Other events: 33 other events

Deaths: 0 deaths

Adalimumab Withdrawal Arm

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Adalimumab 40 mg Eow Rescue Arm

Serious events: 3 serious events

Other events: 13 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Adalimumab 40 mg Eow n=146 participants at risk 40 mg adalimumab administered subcutaneously every other week (eow) from Week 0 to Week 4	Adalimumab Tapering n=102 participants at risk 40 mg adalimumab administered subcutaneously every three weeks from Week 4 to Week 40 (Double-blind Period)	Adalimumab Withdrawal Arm n=20 participants at risk Placebo administered subcutaneously every three weeks from Week 4 to Week 40 (Double-blind Period)	Adalimumab 40 mg Eow Rescue Arm n=39 participants at risk 40 mg adalimumab administered subcutaneously every other week from Flare Week 0 to Flare Week 16 (Open-label Rescue Period)
Cardiac disorders ATRIAL FIBRILLATION	0.68% 1/146 • Number of events 1 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from first dose of study drug until 70 days after the last dose of study drug in the Double-blind Period (up to 50 weeks); for participants who experienced flare during the double-blind period, AEs were collected until 70 days after the last dose of study drug in the 16-week Open-label Rescue Period (up to 66 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is on or after the first dose of study drug until 70 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.	0.00% 0/102 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from first dose of study drug until 70 days after the last dose of study drug in the Double-blind Period (up to 50 weeks); for participants who experienced flare during the double-blind period, AEs were collected until 70 days after the last dose of study drug in the 16-week Open-label Rescue Period (up to 66 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is on or after the first dose of study drug until 70 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.	0.00% 0/20 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from first dose of study drug until 70 days after the last dose of study drug in the Double-blind Period (up to 50 weeks); for participants who experienced flare during the double-blind period, AEs were collected until 70 days after the last dose of study drug in the 16-week Open-label Rescue Period (up to 66 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is on or after the first dose of study drug until 70 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.	0.00% 0/39 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from first dose of study drug until 70 days after the last dose of study drug in the Double-blind Period (up to 50 weeks); for participants who experienced flare during the double-blind period, AEs were collected until 70 days after the last dose of study drug in the 16-week Open-label Rescue Period (up to 66 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is on or after the first dose of study drug until 70 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.
Eye disorders RETINAL VEIN OCCLUSION	0.00% 0/146 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from first dose of study drug until 70 days after the last dose of study drug in the Double-blind Period (up to 50 weeks); for participants who experienced flare during the double-blind period, AEs were collected until 70 days after the last dose of study drug in the 16-week Open-label Rescue Period (up to 66 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is on or after the first dose of study drug until 70 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.	0.00% 0/102 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from first dose of study drug until 70 days after the last dose of study drug in the Double-blind Period (up to 50 weeks); for participants who experienced flare during the double-blind period, AEs were collected until 70 days after the last dose of study drug in the 16-week Open-label Rescue Period (up to 66 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is on or after the first dose of study drug until 70 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.	0.00% 0/20 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from first dose of study drug until 70 days after the last dose of study drug in the Double-blind Period (up to 50 weeks); for participants who experienced flare during the double-blind period, AEs were collected until 70 days after the last dose of study drug in the 16-week Open-label Rescue Period (up to 66 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is on or after the first dose of study drug until 70 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.	2.6% 1/39 • Number of events 1 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from first dose of study drug until 70 days after the last dose of study drug in the Double-blind Period (up to 50 weeks); for participants who experienced flare during the double-blind period, AEs were collected until 70 days after the last dose of study drug in the 16-week Open-label Rescue Period (up to 66 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is on or after the first dose of study drug until 70 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.
Infections and infestations PNEUMONIA	0.68% 1/146 • Number of events 1 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from first dose of study drug until 70 days after the last dose of study drug in the Double-blind Period (up to 50 weeks); for participants who experienced flare during the double-blind period, AEs were collected until 70 days after the last dose of study drug in the 16-week Open-label Rescue Period (up to 66 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is on or after the first dose of study drug until 70 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.	0.00% 0/102 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from first dose of study drug until 70 days after the last dose of study drug in the Double-blind Period (up to 50 weeks); for participants who experienced flare during the double-blind period, AEs were collected until 70 days after the last dose of study drug in the 16-week Open-label Rescue Period (up to 66 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is on or after the first dose of study drug until 70 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.	0.00% 0/20 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from first dose of study drug until 70 days after the last dose of study drug in the Double-blind Period (up to 50 weeks); for participants who experienced flare during the double-blind period, AEs were collected until 70 days after the last dose of study drug in the 16-week Open-label Rescue Period (up to 66 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is on or after the first dose of study drug until 70 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.	0.00% 0/39 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from first dose of study drug until 70 days after the last dose of study drug in the Double-blind Period (up to 50 weeks); for participants who experienced flare during the double-blind period, AEs were collected until 70 days after the last dose of study drug in the 16-week Open-label Rescue Period (up to 66 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is on or after the first dose of study drug until 70 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.
Injury, poisoning and procedural complications COMMINUTED FRACTURE	0.68% 1/146 • Number of events 1 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from first dose of study drug until 70 days after the last dose of study drug in the Double-blind Period (up to 50 weeks); for participants who experienced flare during the double-blind period, AEs were collected until 70 days after the last dose of study drug in the 16-week Open-label Rescue Period (up to 66 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is on or after the first dose of study drug until 70 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.	0.00% 0/102 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from first dose of study drug until 70 days after the last dose of study drug in the Double-blind Period (up to 50 weeks); for participants who experienced flare during the double-blind period, AEs were collected until 70 days after the last dose of study drug in the 16-week Open-label Rescue Period (up to 66 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is on or after the first dose of study drug until 70 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.	0.00% 0/20 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from first dose of study drug until 70 days after the last dose of study drug in the Double-blind Period (up to 50 weeks); for participants who experienced flare during the double-blind period, AEs were collected until 70 days after the last dose of study drug in the 16-week Open-label Rescue Period (up to 66 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is on or after the first dose of study drug until 70 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.	0.00% 0/39 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from first dose of study drug until 70 days after the last dose of study drug in the Double-blind Period (up to 50 weeks); for participants who experienced flare during the double-blind period, AEs were collected until 70 days after the last dose of study drug in the 16-week Open-label Rescue Period (up to 66 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is on or after the first dose of study drug until 70 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.
Musculoskeletal and connective tissue disorders OSTEOARTHRITIS	0.00% 0/146 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from first dose of study drug until 70 days after the last dose of study drug in the Double-blind Period (up to 50 weeks); for participants who experienced flare during the double-blind period, AEs were collected until 70 days after the last dose of study drug in the 16-week Open-label Rescue Period (up to 66 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is on or after the first dose of study drug until 70 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.	0.00% 0/102 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from first dose of study drug until 70 days after the last dose of study drug in the Double-blind Period (up to 50 weeks); for participants who experienced flare during the double-blind period, AEs were collected until 70 days after the last dose of study drug in the 16-week Open-label Rescue Period (up to 66 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is on or after the first dose of study drug until 70 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.	0.00% 0/20 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from first dose of study drug until 70 days after the last dose of study drug in the Double-blind Period (up to 50 weeks); for participants who experienced flare during the double-blind period, AEs were collected until 70 days after the last dose of study drug in the 16-week Open-label Rescue Period (up to 66 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is on or after the first dose of study drug until 70 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.	2.6% 1/39 • Number of events 1 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from first dose of study drug until 70 days after the last dose of study drug in the Double-blind Period (up to 50 weeks); for participants who experienced flare during the double-blind period, AEs were collected until 70 days after the last dose of study drug in the 16-week Open-label Rescue Period (up to 66 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is on or after the first dose of study drug until 70 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) BREAST CANCER	0.00% 0/146 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from first dose of study drug until 70 days after the last dose of study drug in the Double-blind Period (up to 50 weeks); for participants who experienced flare during the double-blind period, AEs were collected until 70 days after the last dose of study drug in the 16-week Open-label Rescue Period (up to 66 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is on or after the first dose of study drug until 70 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.	0.98% 1/102 • Number of events 1 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from first dose of study drug until 70 days after the last dose of study drug in the Double-blind Period (up to 50 weeks); for participants who experienced flare during the double-blind period, AEs were collected until 70 days after the last dose of study drug in the 16-week Open-label Rescue Period (up to 66 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is on or after the first dose of study drug until 70 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.	0.00% 0/20 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from first dose of study drug until 70 days after the last dose of study drug in the Double-blind Period (up to 50 weeks); for participants who experienced flare during the double-blind period, AEs were collected until 70 days after the last dose of study drug in the 16-week Open-label Rescue Period (up to 66 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is on or after the first dose of study drug until 70 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.	0.00% 0/39 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from first dose of study drug until 70 days after the last dose of study drug in the Double-blind Period (up to 50 weeks); for participants who experienced flare during the double-blind period, AEs were collected until 70 days after the last dose of study drug in the 16-week Open-label Rescue Period (up to 66 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is on or after the first dose of study drug until 70 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.
Nervous system disorders TRANSIENT ISCHAEMIC ATTACK	0.68% 1/146 • Number of events 1 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from first dose of study drug until 70 days after the last dose of study drug in the Double-blind Period (up to 50 weeks); for participants who experienced flare during the double-blind period, AEs were collected until 70 days after the last dose of study drug in the 16-week Open-label Rescue Period (up to 66 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is on or after the first dose of study drug until 70 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.	0.00% 0/102 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from first dose of study drug until 70 days after the last dose of study drug in the Double-blind Period (up to 50 weeks); for participants who experienced flare during the double-blind period, AEs were collected until 70 days after the last dose of study drug in the 16-week Open-label Rescue Period (up to 66 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is on or after the first dose of study drug until 70 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.	0.00% 0/20 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from first dose of study drug until 70 days after the last dose of study drug in the Double-blind Period (up to 50 weeks); for participants who experienced flare during the double-blind period, AEs were collected until 70 days after the last dose of study drug in the 16-week Open-label Rescue Period (up to 66 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is on or after the first dose of study drug until 70 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.	0.00% 0/39 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from first dose of study drug until 70 days after the last dose of study drug in the Double-blind Period (up to 50 weeks); for participants who experienced flare during the double-blind period, AEs were collected until 70 days after the last dose of study drug in the 16-week Open-label Rescue Period (up to 66 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is on or after the first dose of study drug until 70 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.
Respiratory, thoracic and mediastinal disorders PLEURAL EFFUSION	0.00% 0/146 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from first dose of study drug until 70 days after the last dose of study drug in the Double-blind Period (up to 50 weeks); for participants who experienced flare during the double-blind period, AEs were collected until 70 days after the last dose of study drug in the 16-week Open-label Rescue Period (up to 66 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is on or after the first dose of study drug until 70 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.	0.00% 0/102 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from first dose of study drug until 70 days after the last dose of study drug in the Double-blind Period (up to 50 weeks); for participants who experienced flare during the double-blind period, AEs were collected until 70 days after the last dose of study drug in the 16-week Open-label Rescue Period (up to 66 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is on or after the first dose of study drug until 70 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.	0.00% 0/20 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from first dose of study drug until 70 days after the last dose of study drug in the Double-blind Period (up to 50 weeks); for participants who experienced flare during the double-blind period, AEs were collected until 70 days after the last dose of study drug in the 16-week Open-label Rescue Period (up to 66 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is on or after the first dose of study drug until 70 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.	2.6% 1/39 • Number of events 1 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from first dose of study drug until 70 days after the last dose of study drug in the Double-blind Period (up to 50 weeks); for participants who experienced flare during the double-blind period, AEs were collected until 70 days after the last dose of study drug in the 16-week Open-label Rescue Period (up to 66 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is on or after the first dose of study drug until 70 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.

Other adverse events

Additional Information

Global Medical Services

AbbVie

Phone: 800-633-9110

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee AbbVie requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. AbbVie requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if AbbVie needs to secure patent or proprietary protection.
Publication restrictions are in place

Restriction type: OTHER

Measure	Non-Flared Participants n=76 Participants Participants who did not experience flare during the Double-blind Period	Flared Participants n=46 Participants Participants who experienced flare during the Double-blind Period	CDAI ≤ 2.8 Clinical Disease Activity Index (CDAI) score ≤ 2.8
Mean Change From Double-blind Baseline in Swollen Joint Count 28 Double Blind Week 10- Tapering Arm	0.1 swollen joint counts Standard Deviation 0.58	0.9 swollen joint counts Standard Deviation 2.09	—
Mean Change From Double-blind Baseline in Swollen Joint Count 28 Double Blind Week 10- Withdrawal Arm	-0.1 swollen joint counts Standard Deviation 0.30	0.1 swollen joint counts Standard Deviation 0.33	—
Mean Change From Double-blind Baseline in Swollen Joint Count 28 Double Blind Week 16- Tapering Arm	-0.0 swollen joint counts Standard Deviation 0.34	1.2 swollen joint counts Standard Deviation 2.15	—
Mean Change From Double-blind Baseline in Swollen Joint Count 28 Double Blind Week 16- Withdrawal Arm	0.0 swollen joint counts Standard Deviation 0.45	0.3 swollen joint counts Standard Deviation 0.50	—
Mean Change From Double-blind Baseline in Swollen Joint Count 28 Double Blind Week 22- Tapering Arm	0.1 swollen joint counts Standard Deviation 0.64	0.6 swollen joint counts Standard Deviation 1.64	—
Mean Change From Double-blind Baseline in Swollen Joint Count 28 Double Blind Week 22- Withdrawal arm	-0.1 swollen joint counts Standard Deviation 0.30	0.5 swollen joint counts Standard Deviation 0.58	—
Mean Change From Double-blind Baseline in Swollen Joint Count 28 Double Blind Week 28- Tapering arm	0.0 swollen joint counts Standard Deviation 0.33	0.5 swollen joint counts Standard Deviation 0.89	—
Mean Change From Double-blind Baseline in Swollen Joint Count 28 Double Blind Week 28- Withdrawal Arm	-0.1 swollen joint counts Standard Deviation 0.30	2.0 swollen joint counts Standard Deviation 2.45	—
Mean Change From Double-blind Baseline in Swollen Joint Count 28 Double Blind Week 34- Tapering Arm	0.0 swollen joint counts Standard Deviation 0.46	0.0 swollen joint counts Standard Deviation 0.43	—
Mean Change From Double-blind Baseline in Swollen Joint Count 28 Double Blind Week 34- Withdrawal Arm	-0.1 swollen joint counts Standard Deviation 0.30	0.0 swollen joint counts Standard Deviation 0.00	—
Mean Change From Double-blind Baseline in Swollen Joint Count 28 Double Blind Week 40- Tapering Arm	0.0 swollen joint counts Standard Deviation 0.42	1.5 swollen joint counts Standard Deviation 3.01	—
Mean Change From Double-blind Baseline in Swollen Joint Count 28 Double Blind Week 40- Withdrawal Arm	-0.1 swollen joint counts Standard Deviation 0.30	2.0 swollen joint counts Standard Deviation 2.83	—
Mean Change From Double-blind Baseline in Swollen Joint Count 28 Flare Week 0- Tapering Arm	—	2.3 swollen joint counts Standard Deviation 2.60	—
Mean Change From Double-blind Baseline in Swollen Joint Count 28 Flare Week 0- Withdrawal Arm	—	1.9 swollen joint counts Standard Deviation 2.10	—
Mean Change From Double-blind Baseline in Swollen Joint Count 28 Flare Week 4- Tapering Arm	—	1.2 swollen joint counts Standard Deviation 1.98	—
Mean Change From Double-blind Baseline in Swollen Joint Count 28 Flare Week 4- Withdrawal Arm	—	0.6 swollen joint counts Standard Deviation 1.06	—
Mean Change From Double-blind Baseline in Swollen Joint Count 28 Flare Week 10- Tapering Arm	—	0.4 swollen joint counts Standard Deviation 0.89	—
Mean Change From Double-blind Baseline in Swollen Joint Count 28 Flare Week 10- Withdrawal Arm	—	0.1 swollen joint counts Standard Deviation 0.35	—
Mean Change From Double-blind Baseline in Swollen Joint Count 28 Flare Week 16- Tapering Arm	—	0.9 swollen joint counts Standard Deviation 1.81	—
Mean Change From Double-blind Baseline in Swollen Joint Count 28 Flare Week 16- Withdrawal Arm	—	0.3 swollen joint counts Standard Deviation 0.46	—

Measure	Non-Flared Participants n=76 Participants Participants who did not experience flare during the Double-blind Period	Flared Participants n=46 Participants Participants who experienced flare during the Double-blind Period	CDAI ≤ 2.8 Clinical Disease Activity Index (CDAI) score ≤ 2.8
Mean Change From Double-blind Baseline in Swollen Joint Count 66 Double Blind Week 10- Tapering Arm	0.1 swollen joint counts Standard Deviation 0.67	1.1 swollen joint counts Standard Deviation 2.36	—
Mean Change From Double-blind Baseline in Swollen Joint Count 66 Double Blind Week 10- Withdrawal Arm	-0.2 swollen joint counts Standard Deviation 0.40	0.1 swollen joint counts Standard Deviation 0.33	—
Mean Change From Double-blind Baseline in Swollen Joint Count 66 Double Blind Week 16- Tapering Arm	-0.0 swollen joint counts Standard Deviation 0.34	1.4 swollen joint counts Standard Deviation 2.56	—
Mean Change From Double-blind Baseline in Swollen Joint Count 66 Double Blind Week 16- Withdrawal Arm	0.0 swollen joint counts Standard Deviation 0.45	0.4 swollen joint counts Standard Deviation 0.53	—
Mean Change From Double-blind Baseline in Swollen Joint Count 66 Double Blind Week 22- Tapering Arm	0.1 swollen joint counts Standard Deviation 0.73	0.6 swollen joint counts Standard Deviation 1.64	—
Mean Change From Double-blind Baseline in Swollen Joint Count 66 Double Blind Week 22- Withdrawal arm	-0.1 swollen joint counts Standard Deviation 0.30	1.0 swollen joint counts Standard Deviation 1.41	—
Mean Change From Double-blind Baseline in Swollen Joint Count 66 Double Blind Week 28- Tapering arm	0.1 swollen joint counts Standard Deviation 0.66	0.5 swollen joint counts Standard Deviation 0.89	—
Mean Change From Double-blind Baseline in Swollen Joint Count 66 Double Blind Week 28- Withdrawal Arm	-0.2 swollen joint counts Standard Deviation 0.40	3.3 swollen joint counts Standard Deviation 4.72	—
Mean Change From Double-blind Baseline in Swollen Joint Count 66 Double Blind Week 34- Tapering Arm	0.0 swollen joint counts Standard Deviation 0.54	0.0 swollen joint counts Standard Deviation 0.43	—
Mean Change From Double-blind Baseline in Swollen Joint Count 66 Double Blind Week 34- Withdrawal Arm	-0.2 swollen joint counts Standard Deviation 0.40	0.0 swollen joint counts Standard Deviation 0.00	—
Mean Change From Double-blind Baseline in Swollen Joint Count 66 Double Blind Week 40- Tapering Arm	0.0 swollen joint counts Standard Deviation 0.46	1.5 swollen joint counts Standard Deviation 3.01	—
Mean Change From Double-blind Baseline in Swollen Joint Count 66 Double Blind Week 40- Withdrawal Arm	-0.2 swollen joint counts Standard Deviation 0.40	2.0 swollen joint counts Standard Deviation 2.83	—
Mean Change From Double-blind Baseline in Swollen Joint Count 66 Flare Week 0- Tapering Arm	—	2.6 swollen joint counts Standard Deviation 2.90	—
Mean Change From Double-blind Baseline in Swollen Joint Count 66 Flare Week 0- Withdrawal Arm	—	2.6 swollen joint counts Standard Deviation 3.38	—
Mean Change From Double-blind Baseline in Swollen Joint Count 66 Flare Week 4- Tapering Arm	—	1.3 swollen joint counts Standard Deviation 1.99	—
Mean Change From Double-blind Baseline in Swollen Joint Count 66 Flare Week 4- Withdrawal Arm	—	0.6 swollen joint counts Standard Deviation 1.06	—
Mean Change From Double-blind Baseline in Swollen Joint Count 66 Flare Week 10- Tapering Arm	—	0.6 swollen joint counts Standard Deviation 1.10	—
Mean Change From Double-blind Baseline in Swollen Joint Count 66 Flare Week 10- Withdrawal Arm	—	0.4 swollen joint counts Standard Deviation 0.52	—
Mean Change From Double-blind Baseline in Swollen Joint Count 66 Flare Week 16- Tapering Arm	—	1.1 swollen joint counts Standard Deviation 2.21	—
Mean Change From Double-blind Baseline in Swollen Joint Count 66 Flare Week 16- Withdrawal Arm	—	0.4 swollen joint counts Standard Deviation 0.74	—

Measure	Non-Flared Participants n=76 Participants Participants who did not experience flare during the Double-blind Period	Flared Participants n=46 Participants Participants who experienced flare during the Double-blind Period	CDAI ≤ 2.8 Clinical Disease Activity Index (CDAI) score ≤ 2.8
Mean Change From Double-blind Baseline in Tender Joint Count 28 Double Blind Week 10- Tapering Arm	0.1 tender joint counts Standard Deviation 0.54	1.3 tender joint counts Standard Deviation 2.74	—
Mean Change From Double-blind Baseline in Tender Joint Count 28 Double Blind Week 10- Withdrawal Arm	0.5 tender joint counts Standard Deviation 1.21	-0.1 tender joint counts Standard Deviation 0.60	—
Mean Change From Double-blind Baseline in Tender Joint Count 28 Double Blind Week 16- Tapering Arm	0.1 tender joint counts Standard Deviation 0.41	2.5 tender joint counts Standard Deviation 4.49	—
Mean Change From Double-blind Baseline in Tender Joint Count 28 Double Blind Week 16- Withdrawal Arm	0.0 tender joint counts Standard Deviation 0.00	1.0 tender joint counts Standard Deviation 0.87	—
Mean Change From Double-blind Baseline in Tender Joint Count 28 Double Blind Week 22- Tapering Arm	-0.0 tender joint counts Standard Deviation 0.42	0.9 tender joint counts Standard Deviation 1.66	—
Mean Change From Double-blind Baseline in Tender Joint Count 28 Double Blind Week 22- Withdrawal arm	0.1 tender joint counts Standard Deviation 0.30	0.8 tender joint counts Standard Deviation 1.50	—
Mean Change From Double-blind Baseline in Tender Joint Count 28 Double Blind Week 28- Tapering arm	0.0 tender joint counts Standard Deviation 0.51	1.6 tender joint counts Standard Deviation 3.39	—
Mean Change From Double-blind Baseline in Tender Joint Count 28 Double Blind Week 28- Withdrawal Arm	0.2 tender joint counts Standard Deviation 0.40	1.8 tender joint counts Standard Deviation 2.36	—
Mean Change From Double-blind Baseline in Tender Joint Count 28 Double Blind Week 34- Tapering Arm	-0.0 tender joint counts Standard Deviation 0.42	1.0 tender joint counts Standard Deviation 1.65	—
Mean Change From Double-blind Baseline in Tender Joint Count 28 Double Blind Week 34- Withdrawal Arm	0.0 tender joint counts Standard Deviation 0.00	0.0 tender joint counts Standard Deviation 0.00	—
Mean Change From Double-blind Baseline in Tender Joint Count 28 Double Blind Week 40- Tapering Arm	0.0 tender joint counts Standard Deviation 0.51	2.0 tender joint counts Standard Deviation 2.65	—
Mean Change From Double-blind Baseline in Tender Joint Count 28 Double Blind Week 40- Withdrawal Arm	0.0 tender joint counts Standard Deviation 0.00	3.5 tender joint counts Standard Deviation 4.95	—
Mean Change From Double-blind Baseline in Tender Joint Count 28 Flare Week 0- Tapering Arm	—	4.4 tender joint counts Standard Deviation 4.63	—
Mean Change From Double-blind Baseline in Tender Joint Count 28 Flare Week 0- Withdrawal Arm	—	3.6 tender joint counts Standard Deviation 3.81	—
Mean Change From Double-blind Baseline in Tender Joint Count 28 Flare Week 4- Tapering Arm	—	1.5 tender joint counts Standard Deviation 2.27	—
Mean Change From Double-blind Baseline in Tender Joint Count 28 Flare Week 4- Withdrawal Arm	—	2.5 tender joint counts Standard Deviation 5.13	—
Mean Change From Double-blind Baseline in Tender Joint Count 28 Flare Week 10- Tapering Arm	—	0.9 tender joint counts Standard Deviation 1.84	—
Mean Change From Double-blind Baseline in Tender Joint Count 28 Flare Week 10- Withdrawal Arm	—	1.1 tender joint counts Standard Deviation 1.46	—
Mean Change From Double-blind Baseline in Tender Joint Count 28 Flare Week 16- Tapering Arm	—	1.8 tender joint counts Standard Deviation 2.64	—
Mean Change From Double-blind Baseline in Tender Joint Count 28 Flare Week 16- Withdrawal Arm	—	1.1 tender joint counts Standard Deviation 1.89	—

Measure	Non-Flared Participants n=76 Participants Participants who did not experience flare during the Double-blind Period	Flared Participants n=46 Participants Participants who experienced flare during the Double-blind Period	CDAI ≤ 2.8 Clinical Disease Activity Index (CDAI) score ≤ 2.8
Mean Change From Double-blind Baseline in Tender Joint Count 68 Double Blind Week 10- Tapering Arm	0.3 tender joint counts Standard Deviation 1.47	1.9 tender joint counts Standard Deviation 3.45	—
Mean Change From Double-blind Baseline in Tender Joint Count 68 Double Blind Week 10- Withdrawal Arm	0.9 tender joint counts Standard Deviation 1.64	0.1 tender joint counts Standard Deviation 0.60	—
Mean Change From Double-blind Baseline in Tender Joint Count 68 Double Blind Week 16- Tapering Arm	0.2 tender joint counts Standard Deviation 1.36	3.5 tender joint counts Standard Deviation 6.33	—
Mean Change From Double-blind Baseline in Tender Joint Count 68 Double Blind Week 16- Withdrawal Arm	0.2 tender joint counts Standard Deviation 0.60	1.4 tender joint counts Standard Deviation 1.13	—
Mean Change From Double-blind Baseline in Tender Joint Count 68 Double Blind Week 22- Tapering Arm	0.2 tender joint counts Standard Deviation 1.35	1.2 tender joint counts Standard Deviation 2.27	—
Mean Change From Double-blind Baseline in Tender Joint Count 68 Double Blind Week 22- Withdrawal arm	0.4 tender joint counts Standard Deviation 1.03	2.0 tender joint counts Standard Deviation 2.83	—
Mean Change From Double-blind Baseline in Tender Joint Count 68 Double Blind Week 28- Tapering arm	0.1 tender joint counts Standard Deviation 0.96	2.5 tender joint counts Standard Deviation 5.34	—
Mean Change From Double-blind Baseline in Tender Joint Count 68 Double Blind Week 28- Withdrawal Arm	0.3 tender joint counts Standard Deviation 0.47	3.8 tender joint counts Standard Deviation 4.50	—
Mean Change From Double-blind Baseline in Tender Joint Count 68 Double Blind Week 34- Tapering Arm	0.0 tender joint counts Standard Deviation 0.73	1.9 tender joint counts Standard Deviation 2.87	—
Mean Change From Double-blind Baseline in Tender Joint Count 68 Double Blind Week 34- Withdrawal Arm	0.1 tender joint counts Standard Deviation 0.30	0.0 tender joint counts Standard Deviation 0.00	—
Mean Change From Double-blind Baseline in Tender Joint Count 68 Double Blind Week 40- Tapering Arm	0.0 tender joint counts Standard Deviation 0.68	3.0 tender joint counts Standard Deviation 4.24	—
Mean Change From Double-blind Baseline in Tender Joint Count 68 Double Blind Week 40- Withdrawal Arm	-0.1 tender joint counts Standard Deviation 0.30	9.0 tender joint counts Standard Deviation 12.73	—
Mean Change From Double-blind Baseline in Tender Joint Count 68 Flare Week 0- Tapering Arm	—	6.2 tender joint counts Standard Deviation 6.93	—
Mean Change From Double-blind Baseline in Tender Joint Count 68 Flare Week 0- Withdrawal Arm	—	6.1 tender joint counts Standard Deviation 6.27	—
Mean Change From Double-blind Baseline in Tender Joint Count 68 Flare Week 4- Tapering Arm	—	1.9 tender joint counts Standard Deviation 2.50	—
Mean Change From Double-blind Baseline in Tender Joint Count 68 Flare Week 4- Withdrawal Arm	—	4.1 tender joint counts Standard Deviation 8.48	—
Mean Change From Double-blind Baseline in Tender Joint Count 68 Flare Week 10- Tapering Arm	—	1.5 tender joint counts Standard Deviation 2.69	—
Mean Change From Double-blind Baseline in Tender Joint Count 68 Flare Week 10- Withdrawal Arm	—	2.3 tender joint counts Standard Deviation 2.31	—
Mean Change From Double-blind Baseline in Tender Joint Count 68 Flare Week 16- Tapering Arm	—	2.1 tender joint counts Standard Deviation 3.37	—
Mean Change From Double-blind Baseline in Tender Joint Count 68 Flare Week 16- Withdrawal Arm	—	1.6 tender joint counts Standard Deviation 1.85	—