Trial Outcomes & Findings for Efficacy and Safety of Adalimumab in Patients With Active Uveitis (NCT NCT01138657)

Last Updated: 2021-07-07

Results Overview

Time to treatment failure was analyzed using Kaplan-Meier methods. Treatment failures on or after Week 6 were counted as events. Dropouts for reasons other than treatment failure at any time during the study were censored at the dropout date. To be considered a treatment failure, ≥ 1 of these criteria had to be present in at least 1 eye: * New active, inflammatory chorioretinal or retinal vascular lesions relative to Baseline * Inability to achieve ≤ 0.5+ at Week 6 or a 2-step increase relative to best state achieved at all visits after Week 6 in anterior chamber cell grade or vitreous haze grade * Worsening of best corrected visual acuity by ≥ 15 letters relative to best state achieved. Per protocol, the primary analysis was performed in the Main Study population which included all randomized participants recruited outside Japan; for completeness results are also reported below for the Integrated dataset which includes participants recruited in Japan.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

239 participants

Primary outcome timeframe

From Baseline until end of study (up to 80 weeks)

Results posted on

2021-07-07

Participant Flow

This study includes a Japan sub-study. 239 participants with active non-infectious intermediate uveitis, posterior uveitis, or panuveitis were randomized worldwide, including 223 participants at 67 sites in Australia, Europe, Israel, Latin America, and North America (Main Study), and 16 participants randomized at 7 sites in Japan (Japan sub-study).

Participants were randomized in a 1:1 ratio double-masked fashion stratified by baseline immunosuppressant usage. Participants recruited in the Japan sub-study were randomized in a separate stratum with no stratification by baseline immunosuppressant usage. Study completion was defined as meeting treatment failure or reaching study Week 80.

Participant milestones

Participant milestones
Measure	Placebo Participants received placebo subcutaneous injection at Baseline followed by every other week (eow) dosing starting at Week 1 for up to 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 60 mg/day at study entry followed by a protocol-defined mandatory taper until Week 15.	Adalimumab Participants received adalimumab 80 mg subcutaneous loading dose at Baseline followed by 40 mg doses eow starting at Week 1 for a maximum of 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 60 mg/day at study entry followed by a protocol-defined mandatory taper until Week 15.
Overall Study STARTED	120	119
Overall Study Enrolled in Main Study	112	111
Overall Study Enrolled in Japan Sub-study	8	8
Overall Study COMPLETED	112	101
Overall Study NOT COMPLETED	8	18

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received placebo subcutaneous injection at Baseline followed by every other week (eow) dosing starting at Week 1 for up to 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 60 mg/day at study entry followed by a protocol-defined mandatory taper until Week 15.	Adalimumab Participants received adalimumab 80 mg subcutaneous loading dose at Baseline followed by 40 mg doses eow starting at Week 1 for a maximum of 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 60 mg/day at study entry followed by a protocol-defined mandatory taper until Week 15.
Overall Study Adverse Event	3	10
Overall Study Lack of Efficacy	2	1
Overall Study Lost to Follow-up	0	3
Overall Study Miscellaneous Reasons	3	4

Baseline Characteristics

Efficacy and Safety of Adalimumab in Patients With Active Uveitis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=120 Participants Participants received placebo subcutaneous injection at Baseline followed by eow dosing starting at Week 1 for up to 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 60 mg/day at study entry followed by a protocol-defined mandatory taper until Week 15.	Adalimumab n=119 Participants Participants received adalimumab 80 mg subcutaneous loading dose at Baseline followed by 40 mg doses eow starting at Week 1 for a maximum of 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 60 mg/day at study entry followed by a protocol-defined mandatory taper until Week 15.	Total n=239 Participants Total of all reporting groups
Age, Continuous	43.19 years STANDARD_DEVIATION 14.331 • n=5 Participants	43.46 years STANDARD_DEVIATION 15.458 • n=7 Participants	43.33 years STANDARD_DEVIATION 14.872 • n=5 Participants
Age, Customized < 40 years	56 participants n=5 Participants	47 participants n=7 Participants	103 participants n=5 Participants
Age, Customized 40 - 64 years	54 participants n=5 Participants	56 participants n=7 Participants	110 participants n=5 Participants
Age, Customized ≥ 65 years	10 participants n=5 Participants	16 participants n=7 Participants	26 participants n=5 Participants
Sex: Female, Male Female	73 Participants n=5 Participants	66 Participants n=7 Participants	139 Participants n=5 Participants
Sex: Female, Male Male	47 Participants n=5 Participants	53 Participants n=7 Participants	100 Participants n=5 Participants
Race/Ethnicity, Customized White	91 participants n=5 Participants	89 participants n=7 Participants	180 participants n=5 Participants
Race/Ethnicity, Customized Black	12 participants n=5 Participants	11 participants n=7 Participants	23 participants n=5 Participants
Race/Ethnicity, Customized Asian	10 participants n=5 Participants	12 participants n=7 Participants	22 participants n=5 Participants
Race/Ethnicity, Customized American Indian/Alaskan Native	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
Race/Ethnicity, Customized Other	5 participants n=5 Participants	6 participants n=7 Participants	11 participants n=5 Participants
Race/Ethnicity, Customized Multi Race	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants
Type of Uveitis Intermediate	24 participants n=5 Participants	25 participants n=7 Participants	49 participants n=5 Participants
Type of Uveitis Posterior	38 participants n=5 Participants	38 participants n=7 Participants	76 participants n=5 Participants
Type of Uveitis Panuveitis	58 participants n=5 Participants	56 participants n=7 Participants	114 participants n=5 Participants
Diagnosis Idiopathic	50 participants n=5 Participants	40 participants n=7 Participants	90 participants n=5 Participants
Diagnosis Birdshot Choroidopathy	21 participants n=5 Participants	24 participants n=7 Participants	45 participants n=5 Participants
Diagnosis Multifocal Choroiditis And Panuveitis	5 participants n=5 Participants	8 participants n=7 Participants	13 participants n=5 Participants
Diagnosis Vogt Koyanagi Harada	14 participants n=5 Participants	12 participants n=7 Participants	26 participants n=5 Participants
Diagnosis Sarcoid	12 participants n=5 Participants	12 participants n=7 Participants	24 participants n=5 Participants
Diagnosis Behcet's	4 participants n=5 Participants	14 participants n=7 Participants	18 participants n=5 Participants
Diagnosis Other	14 participants n=5 Participants	9 participants n=7 Participants	23 participants n=5 Participants
Eye Affected Left	5 participants n=5 Participants	6 participants n=7 Participants	11 participants n=5 Participants
Eye Affected Right	4 participants n=5 Participants	7 participants n=7 Participants	11 participants n=5 Participants
Eye Affected Both	111 participants n=5 Participants	106 participants n=7 Participants	217 participants n=5 Participants
Duration of Uveitis	58.56 months STANDARD_DEVIATION 85.308 • n=5 Participants	41.18 months STANDARD_DEVIATION 53.530 • n=7 Participants	49.90 months STANDARD_DEVIATION 71.660 • n=5 Participants

PRIMARY outcome

Timeframe: From Baseline until end of study (up to 80 weeks)

Population: The intent-to-treat (ITT) population which included all randomized participants; 6 participants at 2 sites were excluded from the ITT due to incomplete efficacy source data and compliance issues.

Outcome measures

Outcome measures
Measure	Main Study: Placebo n=107 Participants Participants, excluding those enrolled in the Japan sub-study, received placebo subcutaneous injection at Baseline followed by eow dosing starting at Week 1 for up to 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 60 mg/day at study entry followed by a protocol-defined mandatory taper until Week 15.	Main Study: Adalimumab n=110 Participants Participants, excluding those enrolled in the Japan sub-study, received adalimumab 80 mg subcutaneous loading dose at Baseline followed by 40 mg doses every other week (eow) starting at Week 1 for a maximum of 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 60 mg/day at study entry followed by a protocol-defined mandatory taper until Week 15.	Integrated Study (Main + Japan Sub-study): Placebo n=115 Participants Participants, including those enrolled in the Main Study and the Japan Sub-study, received placebo subcutaneous injection at Baseline followed by eow dosing starting at Week 1 for up to 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 60 mg/day at study entry followed by a protocol-defined mandatory taper until Week 15.	Integrated Study (Main + Japan Sub-study): Adalimumab n=118 Participants Participants, including those enrolled in the Main Study and the Japan Sub-study, received adalimumab 80 mg subcutaneous loading dose at Baseline followed by 40 mg doses every other week (eow) starting at Week 1 for a maximum of 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 60 mg/day at study entry followed by a protocol-defined mandatory taper until Week 15.
Time to Treatment Failure on or After Week 6	3.0 months Interval 1.5 to 5.6	5.6 months Interval 3.0 to Not estimable due to the low number of events	3.0 months Interval 1.5 to 5.6	4.8 months Interval 2.8 to Not estimable due to the low number of events

SECONDARY outcome

Timeframe: From Baseline to Week 6 and at the Final/Early Termination Visit (up to 80 weeks)

Population: Intent-to-treat population with values at both time points (best state achieved prior to Week 6 and at least 1 post-week 6 value); last observation carried forward (LOCF) imputation was used; participants with no values after Week 6 were excluded.

Slit lamp examinations were conducted at each visit to assess AC cell count. The number of AC cells observed within a 1 mm × 1 mm slit beam was used to determine the grade according to the Standardization of Uveitis Nomenclature (SUN) criteria: Grade 0 = \< 1 cell; Grade 0.5+ = 1-5 cells; Grade 1+ = 6-15 cells; Grade 2+ = 16-25 cells; Grade 3+ = 26-50 cells; Grade 4+ = \> 50 cells.

Outcome measures

Outcome measures
Measure	Main Study: Placebo n=102 Participants Participants, excluding those enrolled in the Japan sub-study, received placebo subcutaneous injection at Baseline followed by eow dosing starting at Week 1 for up to 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 60 mg/day at study entry followed by a protocol-defined mandatory taper until Week 15.	Main Study: Adalimumab n=101 Participants Participants, excluding those enrolled in the Japan sub-study, received adalimumab 80 mg subcutaneous loading dose at Baseline followed by 40 mg doses every other week (eow) starting at Week 1 for a maximum of 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 60 mg/day at study entry followed by a protocol-defined mandatory taper until Week 15.	Integrated Study (Main + Japan Sub-study): Placebo n=110 Participants Participants, including those enrolled in the Main Study and the Japan Sub-study, received placebo subcutaneous injection at Baseline followed by eow dosing starting at Week 1 for up to 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 60 mg/day at study entry followed by a protocol-defined mandatory taper until Week 15.	Integrated Study (Main + Japan Sub-study): Adalimumab n=109 Participants Participants, including those enrolled in the Main Study and the Japan Sub-study, received adalimumab 80 mg subcutaneous loading dose at Baseline followed by 40 mg doses every other week (eow) starting at Week 1 for a maximum of 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 60 mg/day at study entry followed by a protocol-defined mandatory taper until Week 15.
Change in Anterior Chamber (AC) Cell Grade in Each Eye From Best State Achieved Prior to Week 6 to the Final/Early Termination Visit Left Eye	0.59 units on a scale Standard Deviation 0.935	0.35 units on a scale Standard Deviation 0.763	0.56 units on a scale Standard Deviation 0.913	0.35 units on a scale Standard Deviation 0.744
Change in Anterior Chamber (AC) Cell Grade in Each Eye From Best State Achieved Prior to Week 6 to the Final/Early Termination Visit Right Eye	0.69 units on a scale Standard Deviation 1.067	0.36 units on a scale Standard Deviation 0.746	0.65 units on a scale Standard Deviation 1.039	0.36 units on a scale Standard Deviation 0.727

SECONDARY outcome

Timeframe: From Baseline to Week 6 and Final/Early Termination Visit (up to 80 weeks)

Population: Intent-to-treat population with values at both time points; last observation carried forward (LOCF) imputation was used; participants with no values after Week 6 were excluded.

Vitreous haze was measured using dilated indirect ophthalmoscopy (DIO) and assessed by the Investigator according to National Eye Institute (NEI) and SUN criteria: Grade 0: No evident vitreous haze; Grade 0.5+: Slight blurring of the optic disc margin because of the haze; normal striations and reflex of the nerve fiber layer cannot be visualized; Grade 1+: Permits a better definition of both the optic nerve head and the retinal vessels (compared to higher grades); Grade 2+: Permits better visualization of the retinal vessels (compared to higher grades); Grade 3+: Permits the observer to see the optic nerve head, but the borders are quite blurry; Grade 4+: Optic nerve head is obscured.

Outcome measures

Outcome measures
Measure	Main Study: Placebo n=103 Participants Participants, excluding those enrolled in the Japan sub-study, received placebo subcutaneous injection at Baseline followed by eow dosing starting at Week 1 for up to 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 60 mg/day at study entry followed by a protocol-defined mandatory taper until Week 15.	Main Study: Adalimumab n=101 Participants Participants, excluding those enrolled in the Japan sub-study, received adalimumab 80 mg subcutaneous loading dose at Baseline followed by 40 mg doses every other week (eow) starting at Week 1 for a maximum of 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 60 mg/day at study entry followed by a protocol-defined mandatory taper until Week 15.	Integrated Study (Main + Japan Sub-study): Placebo n=111 Participants Participants, including those enrolled in the Main Study and the Japan Sub-study, received placebo subcutaneous injection at Baseline followed by eow dosing starting at Week 1 for up to 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 60 mg/day at study entry followed by a protocol-defined mandatory taper until Week 15.	Integrated Study (Main + Japan Sub-study): Adalimumab n=109 Participants Participants, including those enrolled in the Main Study and the Japan Sub-study, received adalimumab 80 mg subcutaneous loading dose at Baseline followed by 40 mg doses every other week (eow) starting at Week 1 for a maximum of 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 60 mg/day at study entry followed by a protocol-defined mandatory taper until Week 15.
Change in Vitreous Haze (VH) Grade in Each Eye From Best State Achieved Prior to Week 6 to the Final/Early Termination Visit Right Eye	0.45 units on a scale Standard Deviation 0.781	0.13 units on a scale Standard Deviation 0.648	0.49 units on a scale Standard Deviation 0.815	0.16 units on a scale Standard Deviation 0.648
Change in Vitreous Haze (VH) Grade in Each Eye From Best State Achieved Prior to Week 6 to the Final/Early Termination Visit Left Eye	0.33 units on a scale Standard Deviation 0.666	0.11 units on a scale Standard Deviation 0.559	0.34 units on a scale Standard Deviation 0.675	0.11 units on a scale Standard Deviation 0.547

SECONDARY outcome

Timeframe: From Baseline to Week 6 and Final/Early Termination Visit (up to 80 weeks)

Population: Intent-to-treat population with values at both time points; last observation carried forward (LOCF) imputation was used; participants with no values after Week 6 were excluded.

Using corrective lenses based on that visit's refraction testing, participant's best corrected visual acuity was measured using an Early Treatment Diabetic Retinopathy Study (ETDRS) logMAR chart.

Outcome measures

Outcome measures
Measure	Main Study: Placebo n=103 Participants Participants, excluding those enrolled in the Japan sub-study, received placebo subcutaneous injection at Baseline followed by eow dosing starting at Week 1 for up to 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 60 mg/day at study entry followed by a protocol-defined mandatory taper until Week 15.	Main Study: Adalimumab n=101 Participants Participants, excluding those enrolled in the Japan sub-study, received adalimumab 80 mg subcutaneous loading dose at Baseline followed by 40 mg doses every other week (eow) starting at Week 1 for a maximum of 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 60 mg/day at study entry followed by a protocol-defined mandatory taper until Week 15.	Integrated Study (Main + Japan Sub-study): Placebo n=111 Participants Participants, including those enrolled in the Main Study and the Japan Sub-study, received placebo subcutaneous injection at Baseline followed by eow dosing starting at Week 1 for up to 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 60 mg/day at study entry followed by a protocol-defined mandatory taper until Week 15.	Integrated Study (Main + Japan Sub-study): Adalimumab n=109 Participants Participants, including those enrolled in the Main Study and the Japan Sub-study, received adalimumab 80 mg subcutaneous loading dose at Baseline followed by 40 mg doses every other week (eow) starting at Week 1 for a maximum of 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 60 mg/day at study entry followed by a protocol-defined mandatory taper until Week 15.
Change In Logarithm of the Minimum Angle of Resolution (LogMAR) Best Corrected Visual Acuity (BCVA) In Each Eye From Best State Achieved Prior to Week 6 to the Final/Early Termination Visit Left Eye	0.12 logMAR Standard Deviation 0.169	0.07 logMAR Standard Deviation 0.160	0.11 logMAR Standard Deviation 0.179	0.07 logMAR Standard Deviation 0.164
Change In Logarithm of the Minimum Angle of Resolution (LogMAR) Best Corrected Visual Acuity (BCVA) In Each Eye From Best State Achieved Prior to Week 6 to the Final/Early Termination Visit Right Eye	0.13 logMAR Standard Deviation 0.320	0.04 logMAR Standard Deviation 0.143	0.13 logMAR Standard Deviation 0.328	0.05 logMAR Standard Deviation 0.145

SECONDARY outcome

Timeframe: From Baseline until the Final Visit (up to 80 weeks)

Population: Intent to treat population with no macular edema at Baseline

Optical coherence tomography was performed at every visit using 1 of 3 approved machines. Images were evaluated by a central reader. Macular edema was defined as cystoid macular edema. OCT evidence of macular edema on or after Week 6 was to be counted as an event. Dropouts due to reasons other than OCT evidence of macular edema were to be considered as censored observations at the time of dropping out.

Outcome measures

Outcome measures
Measure	Main Study: Placebo n=45 Participants Participants, excluding those enrolled in the Japan sub-study, received placebo subcutaneous injection at Baseline followed by eow dosing starting at Week 1 for up to 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 60 mg/day at study entry followed by a protocol-defined mandatory taper until Week 15.	Main Study: Adalimumab n=55 Participants Participants, excluding those enrolled in the Japan sub-study, received adalimumab 80 mg subcutaneous loading dose at Baseline followed by 40 mg doses every other week (eow) starting at Week 1 for a maximum of 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 60 mg/day at study entry followed by a protocol-defined mandatory taper until Week 15.	Integrated Study (Main + Japan Sub-study): Placebo n=47 Participants Participants, including those enrolled in the Main Study and the Japan Sub-study, received placebo subcutaneous injection at Baseline followed by eow dosing starting at Week 1 for up to 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 60 mg/day at study entry followed by a protocol-defined mandatory taper until Week 15.	Integrated Study (Main + Japan Sub-study): Adalimumab n=57 Participants Participants, including those enrolled in the Main Study and the Japan Sub-study, received adalimumab 80 mg subcutaneous loading dose at Baseline followed by 40 mg doses every other week (eow) starting at Week 1 for a maximum of 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 60 mg/day at study entry followed by a protocol-defined mandatory taper until Week 15.
Time to Optical Coherence Tomography (OCT) Evidence of Macular Edema in At Least 1 Eye On or After Week 6	6.2 months Interval 1.4 to Could not be estimated due to the low number of events	11.1 months Interval 2.6 to 15.9	3.7 months Interval 1.4 to Could not be estimated due to the low number of events	9.2 months Interval 2.7 to 15.9

SECONDARY outcome

Timeframe: Baseline to Week 6 and Final/Early Termination Visit (up to 80 weeks)

Population: Intent-to-treat population with values at both time points; last observation carried forward (LOCF) imputation was used; participants with no values after Week 6 were excluded.

Central retinal thickness was measured using optical coherence tomography and assessed by a central reader.

Outcome measures

Outcome measures
Measure	Main Study: Placebo n=102 Participants Participants, excluding those enrolled in the Japan sub-study, received placebo subcutaneous injection at Baseline followed by eow dosing starting at Week 1 for up to 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 60 mg/day at study entry followed by a protocol-defined mandatory taper until Week 15.	Main Study: Adalimumab n=101 Participants Participants, excluding those enrolled in the Japan sub-study, received adalimumab 80 mg subcutaneous loading dose at Baseline followed by 40 mg doses every other week (eow) starting at Week 1 for a maximum of 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 60 mg/day at study entry followed by a protocol-defined mandatory taper until Week 15.	Integrated Study (Main + Japan Sub-study): Placebo n=108 Participants Participants, including those enrolled in the Main Study and the Japan Sub-study, received placebo subcutaneous injection at Baseline followed by eow dosing starting at Week 1 for up to 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 60 mg/day at study entry followed by a protocol-defined mandatory taper until Week 15.	Integrated Study (Main + Japan Sub-study): Adalimumab n=109 Participants Participants, including those enrolled in the Main Study and the Japan Sub-study, received adalimumab 80 mg subcutaneous loading dose at Baseline followed by 40 mg doses every other week (eow) starting at Week 1 for a maximum of 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 60 mg/day at study entry followed by a protocol-defined mandatory taper until Week 15.
Percent Change in Central Retinal Thickness in Each Eye From Best State Achieved Prior to Week 6 to the Final/Early Termination Visit Left eye (n=100, 100, 107, 108)	20.2 percent change Standard Deviation 52.01	9.6 percent change Standard Deviation 29.76	19.0 percent change Standard Deviation 50.57	13.9 percent change Standard Deviation 53.95
Percent Change in Central Retinal Thickness in Each Eye From Best State Achieved Prior to Week 6 to the Final/Early Termination Visit Right eye (n=102, 101, 108, 109)	22.0 percent change Standard Deviation 62.48	8.2 percent change Standard Deviation 25.78	21.7 percent change Standard Deviation 60.75	14.5 percent change Standard Deviation 57.05

SECONDARY outcome

Timeframe: Baseline to Week 6 and Final/Early Termination Visit (up 80 weeks)

Population: Intent-to-treat population with values at both time points; last observation carried forward (LOCF) imputation was used; participants with no values after Week 6 were excluded.

The National Eye Institute VFQ-25 is an ocular disease-specific survey that measures the influence of visual disability and visual symptoms on generic health domains such as emotional well-being and social functioning, in addition to task-oriented domains related to daily visual functioning. The VFQ-25 consists of a base set of 25 vision-targeted questions plus an additional single-item general health rating question. The overall composite score ranges from 0 to 100, where higher scores or increases in score indicate better vision-related functioning.

Outcome measures

Outcome measures
Measure	Main Study: Placebo n=102 Participants Participants, excluding those enrolled in the Japan sub-study, received placebo subcutaneous injection at Baseline followed by eow dosing starting at Week 1 for up to 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 60 mg/day at study entry followed by a protocol-defined mandatory taper until Week 15.	Main Study: Adalimumab n=101 Participants Participants, excluding those enrolled in the Japan sub-study, received adalimumab 80 mg subcutaneous loading dose at Baseline followed by 40 mg doses every other week (eow) starting at Week 1 for a maximum of 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 60 mg/day at study entry followed by a protocol-defined mandatory taper until Week 15.	Integrated Study (Main + Japan Sub-study): Placebo n=110 Participants Participants, including those enrolled in the Main Study and the Japan Sub-study, received placebo subcutaneous injection at Baseline followed by eow dosing starting at Week 1 for up to 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 60 mg/day at study entry followed by a protocol-defined mandatory taper until Week 15.	Integrated Study (Main + Japan Sub-study): Adalimumab n=109 Participants Participants, including those enrolled in the Main Study and the Japan Sub-study, received adalimumab 80 mg subcutaneous loading dose at Baseline followed by 40 mg doses every other week (eow) starting at Week 1 for a maximum of 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 60 mg/day at study entry followed by a protocol-defined mandatory taper until Week 15.
Change in Visual Functioning Questionnaire 25 (VFQ-25) Composite Score From Best State Achieved Prior to Week 6 to the Final/Early Termination Visit	-5.50 units on a scale Standard Deviation 11.968	-1.30 units on a scale Standard Deviation 10.980	-5.34 units on a scale Standard Deviation 11.899	-1.68 units on a scale Standard Deviation 10.924

SECONDARY outcome

Timeframe: Baseline to Week 6 and Final/Early Termination Visit (up 80 weeks)

Population: Intent-to-treat population with values at both time points; last observation carried forward (LOCF) imputation was used; participants with no values after Week 6 were excluded.

The National Eye Institute VFQ-25 is an ocular disease-specific survey that measures the influence of visual disability and visual symptoms on generic health domains such as emotional well-being and social functioning, in addition to task-oriented domains related to daily visual functioning. The VFQ-25 consists of a base set of 25 vision-targeted questions plus an additional single-item general health rating question. The distance vision subscore is calculated from the answers to 3 distance vision-related questions and ranges from 0 to 100, where higher scores or increases in score indicate better vision-related functioning.

Outcome measures

Outcome measures
Measure	Main Study: Placebo n=102 Participants Participants, excluding those enrolled in the Japan sub-study, received placebo subcutaneous injection at Baseline followed by eow dosing starting at Week 1 for up to 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 60 mg/day at study entry followed by a protocol-defined mandatory taper until Week 15.	Main Study: Adalimumab n=101 Participants Participants, excluding those enrolled in the Japan sub-study, received adalimumab 80 mg subcutaneous loading dose at Baseline followed by 40 mg doses every other week (eow) starting at Week 1 for a maximum of 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 60 mg/day at study entry followed by a protocol-defined mandatory taper until Week 15.	Integrated Study (Main + Japan Sub-study): Placebo n=110 Participants Participants, including those enrolled in the Main Study and the Japan Sub-study, received placebo subcutaneous injection at Baseline followed by eow dosing starting at Week 1 for up to 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 60 mg/day at study entry followed by a protocol-defined mandatory taper until Week 15.	Integrated Study (Main + Japan Sub-study): Adalimumab n=109 Participants Participants, including those enrolled in the Main Study and the Japan Sub-study, received adalimumab 80 mg subcutaneous loading dose at Baseline followed by 40 mg doses every other week (eow) starting at Week 1 for a maximum of 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 60 mg/day at study entry followed by a protocol-defined mandatory taper until Week 15.
Change in VFQ-25 Distance Vision Subscore From Best State Achieved Prior to Week 6 to the Final/Early Termination Visit	-5.64 units on a scale Standard Deviation 14.654	-3.77 units on a scale Standard Deviation 13.414	-5.72 units on a scale Standard Deviation 14.531	-4.42 units on a scale Standard Deviation 13.871

SECONDARY outcome

Timeframe: Baseline to Week 6 and Final/Early Termination Visit (up 80 weeks)

Population: Intent-to-treat population with values at both time points; last observation carried forward (LOCF) imputation was used; participants with no values after Week 6 were excluded.

The National Eye Institute VFQ-25 is an ocular disease-specific survey that measures the influence of visual disability and visual symptoms on generic health domains such as emotional well-being and social functioning, in addition to task-oriented domains related to daily visual functioning. The VFQ-25 consists of a base set of 25 vision-targeted questions plus an additional single-item general health rating question. The distance vision subscore is calculated from the answers to 3 near vision-related questions and ranges from 0 to 100, where higher scores or increases in score indicate better vision-related functioning.

Outcome measures

Outcome measures
Measure	Main Study: Placebo n=102 Participants Participants, excluding those enrolled in the Japan sub-study, received placebo subcutaneous injection at Baseline followed by eow dosing starting at Week 1 for up to 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 60 mg/day at study entry followed by a protocol-defined mandatory taper until Week 15.	Main Study: Adalimumab n=101 Participants Participants, excluding those enrolled in the Japan sub-study, received adalimumab 80 mg subcutaneous loading dose at Baseline followed by 40 mg doses every other week (eow) starting at Week 1 for a maximum of 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 60 mg/day at study entry followed by a protocol-defined mandatory taper until Week 15.	Integrated Study (Main + Japan Sub-study): Placebo n=110 Participants Participants, including those enrolled in the Main Study and the Japan Sub-study, received placebo subcutaneous injection at Baseline followed by eow dosing starting at Week 1 for up to 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 60 mg/day at study entry followed by a protocol-defined mandatory taper until Week 15.	Integrated Study (Main + Japan Sub-study): Adalimumab n=109 Participants Participants, including those enrolled in the Main Study and the Japan Sub-study, received adalimumab 80 mg subcutaneous loading dose at Baseline followed by 40 mg doses every other week (eow) starting at Week 1 for a maximum of 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 60 mg/day at study entry followed by a protocol-defined mandatory taper until Week 15.
Change in VFQ-25 Near Vision Subscore From Best State Achieved Prior to Week 6 to the Final/Early Termination Visit	-8.09 units on a scale Standard Deviation 17.754	-2.97 units on a scale Standard Deviation 16.784	-7.65 units on a scale Standard Deviation 17.808	-3.52 units on a scale Standard Deviation 16.494

SECONDARY outcome

Timeframe: Baseline to Week 6 and Final/Early Termination Visit (up 80 weeks)

Population: Intent-to-treat population with values at both time points; last observation carried forward (LOCF) imputation was used; participants with no values after Week 6 were excluded.

The National Eye Institute VFQ-25 is an ocular disease-specific survey that measures the influence of visual disability and visual symptoms on generic health domains such as emotional well-being and social functioning, in addition to task-oriented domains related to daily visual functioning. The VFQ-25 consists of a base set of 25 vision-targeted questions plus an additional single-item general health rating question. The ocular pain subscore is calculated from the answers to 2 ocular pain-related questions and ranges from 0 to 100, where higher scores or increases in score indicate less pain.

Outcome measures

Outcome measures
Measure	Main Study: Placebo n=102 Participants Participants, excluding those enrolled in the Japan sub-study, received placebo subcutaneous injection at Baseline followed by eow dosing starting at Week 1 for up to 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 60 mg/day at study entry followed by a protocol-defined mandatory taper until Week 15.	Main Study: Adalimumab n=101 Participants Participants, excluding those enrolled in the Japan sub-study, received adalimumab 80 mg subcutaneous loading dose at Baseline followed by 40 mg doses every other week (eow) starting at Week 1 for a maximum of 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 60 mg/day at study entry followed by a protocol-defined mandatory taper until Week 15.	Integrated Study (Main + Japan Sub-study): Placebo n=110 Participants Participants, including those enrolled in the Main Study and the Japan Sub-study, received placebo subcutaneous injection at Baseline followed by eow dosing starting at Week 1 for up to 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 60 mg/day at study entry followed by a protocol-defined mandatory taper until Week 15.	Integrated Study (Main + Japan Sub-study): Adalimumab n=109 Participants Participants, including those enrolled in the Main Study and the Japan Sub-study, received adalimumab 80 mg subcutaneous loading dose at Baseline followed by 40 mg doses every other week (eow) starting at Week 1 for a maximum of 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 60 mg/day at study entry followed by a protocol-defined mandatory taper until Week 15.
Change in VFQ-25 Ocular Pain Subscore From Best State Achieved Prior to Week 6 to the Final/Early Termination Visit	-12.62 units on a scale Standard Deviation 21.435	-2.60 units on a scale Standard Deviation 15.342	-12.39 units on a scale Standard Deviation 20.841	-3.56 units on a scale Standard Deviation 16.056

Adverse Events

Placebo

Serious events: 5 serious events

Other events: 61 other events

Deaths: 0 deaths

Adalimumab

Serious events: 16 serious events

Other events: 71 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Global Medical Services

AbbVie (prior sponsor, Abbott)

Phone: 800-633-9110

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	Placebo n=120 participants at risk Participants received placebo subcutaneous injection at Baseline followed by eow dosing starting at Week 1 for up to 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 60 mg/day at study entry followed by a protocol-defined mandatory taper until Week 15.	Adalimumab n=119 participants at risk Participants received adalimumab 80 mg subcutaneous loading dose at Baseline followed by 40 mg doses eow starting at Week 1 for a maximum of 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 60 mg/day at study entry followed by a protocol-defined mandatory taper until Week 15.
Eye disorders ANGLE CLOSURE GLAUCOMA	0.00% 0/120 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.	0.84% 1/119 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.
Hepatobiliary disorders HEPATITIS ACUTE	0.83% 1/120 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.	0.00% 0/119 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.
Immune system disorders ANAPHYLACTIC REACTION	0.00% 0/120 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.	0.84% 1/119 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.
Infections and infestations GASTROENTERITIS VIRAL	0.83% 1/120 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.	0.00% 0/119 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.
Infections and infestations PILONIDAL CYST	0.00% 0/120 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.	0.84% 1/119 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.
Infections and infestations PNEUMONIA	0.00% 0/120 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.	0.84% 1/119 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.
Infections and infestations PYELONEPHRITIS ACUTE	0.83% 1/120 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.	0.00% 0/119 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.
Infections and infestations SEPSIS	0.83% 1/120 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.	0.00% 0/119 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.
Infections and infestations TUBERCULOSIS	0.00% 0/120 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.	0.84% 1/119 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.
Infections and infestations UPPER RESPIRATORY TRACT INFECTION	0.00% 0/120 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.	0.84% 1/119 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.
Infections and infestations URINARY TRACT INFECTION	0.00% 0/120 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.	0.84% 1/119 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.
Injury, poisoning and procedural complications ACCIDENTAL OVERDOSE	0.00% 0/120 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.	0.84% 1/119 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.
Injury, poisoning and procedural complications LIGAMENT RUPTURE	0.00% 0/120 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.	0.84% 1/119 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.
Injury, poisoning and procedural complications TENDON RUPTURE	0.00% 0/120 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.	0.84% 1/119 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.
Injury, poisoning and procedural complications WRIST FRACTURE	0.83% 1/120 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.	0.00% 0/119 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.
Metabolism and nutrition disorders FLUID OVERLOAD	0.00% 0/120 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.	0.84% 1/119 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.
Musculoskeletal and connective tissue disorders LUPUS-LIKE SYNDROME	0.00% 0/120 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.	0.84% 1/119 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) CARCINOID TUMOUR OF THE GASTROINTESTINAL TRACT	0.00% 0/120 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.	0.84% 1/119 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) GLIOBLASTOMA MULTIFORME	0.00% 0/120 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.	0.84% 1/119 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.
Nervous system disorders DEMYELINATION	0.00% 0/120 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.	0.84% 1/119 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.
Renal and urinary disorders CALCULUS URETERIC	0.00% 0/120 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.	0.84% 1/119 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.
Renal and urinary disorders RENAL FAILURE CHRONIC	0.00% 0/120 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.	0.84% 1/119 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.
Skin and subcutaneous tissue disorders URTICARIA	0.00% 0/120 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.	0.84% 1/119 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.
Surgical and medical procedures ABORTION INDUCED	0.83% 1/120 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.	0.00% 0/119 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.
Vascular disorders NEOVASCULARISATION	0.00% 0/120 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.	0.84% 1/119 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.

Measure	Placebo n=120 participants at risk Participants received placebo subcutaneous injection at Baseline followed by eow dosing starting at Week 1 for up to 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 60 mg/day at study entry followed by a protocol-defined mandatory taper until Week 15.	Adalimumab n=119 participants at risk Participants received adalimumab 80 mg subcutaneous loading dose at Baseline followed by 40 mg doses eow starting at Week 1 for a maximum of 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 60 mg/day at study entry followed by a protocol-defined mandatory taper until Week 15.
Eye disorders CYSTOID MACULAR OEDEMA	5.0% 6/120 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.	2.5% 3/119 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.
Eye disorders EYE PAIN	1.7% 2/120 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.	7.6% 9/119 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.
Eye disorders UVEITIS	6.7% 8/120 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.	10.1% 12/119 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.
Eye disorders VISION BLURRED	1.7% 2/120 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.	6.7% 8/119 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.
Gastrointestinal disorders DRY MOUTH	0.83% 1/120 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.	5.0% 6/119 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.
Gastrointestinal disorders NAUSEA	5.8% 7/120 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.	5.0% 6/119 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.
General disorders FATIGUE	5.8% 7/120 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.	10.1% 12/119 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.
Infections and infestations BRONCHITIS	3.3% 4/120 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.	5.9% 7/119 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.
Infections and infestations INFLUENZA	5.0% 6/120 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.	0.84% 1/119 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.
Infections and infestations NASOPHARYNGITIS	9.2% 11/120 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.	17.6% 21/119 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.
Infections and infestations URINARY TRACT INFECTION	0.00% 0/120 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.	5.0% 6/119 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.
Musculoskeletal and connective tissue disorders ARTHRALGIA	10.0% 12/120 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.	8.4% 10/119 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.
Musculoskeletal and connective tissue disorders BACK PAIN	2.5% 3/120 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.	7.6% 9/119 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.
Musculoskeletal and connective tissue disorders MUSCLE SPASMS	3.3% 4/120 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.	5.9% 7/119 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.
Nervous system disorders HEADACHE	13.3% 16/120 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.	10.9% 13/119 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.
Nervous system disorders PARAESTHESIA	0.00% 0/120 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.	5.0% 6/119 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.
Psychiatric disorders ANXIETY	0.00% 0/120 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.	5.0% 6/119 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.
Psychiatric disorders INSOMNIA	6.7% 8/120 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.	7.6% 9/119 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.
Respiratory, thoracic and mediastinal disorders COUGH	3.3% 4/120 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.	5.9% 7/119 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.
Skin and subcutaneous tissue disorders HYPERHIDROSIS	2.5% 3/120 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.	5.9% 7/119 • From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.