Trial Outcomes & Findings for Efficacy and Safety of Adalimumab in Subjects With Inactive Uveitis (NCT NCT01124838)

Last Updated: 2021-07-07

Results Overview

Treatment failure was defined by the occurrence of a uveitis flare (the inability to maintain disease control). To be considered treatment failure, ≥ 1 of these criteria had to be present in at least 1 eye at Week 2 or all other visits: * New active, inflammatory chorioretinal, and/or inflammatory retinal vascular lesions relative to Baseline * 2-step increase relative to Baseline in anterior chamber cell grade or vitreous haze grade * Worsening of best corrected visual acuity by ≥ 15 letters relative to baseline. Time to treatment failure was analyzed using the Kaplan-Meier method. Dropouts for reasons other than treatment failure at any time during the study were censored at the drop out date. 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

261 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. A total of 261 adults with inactive non-infectious intermediate uveitis, posterior uveitis or panuveitis were randomized at 72 study sites worldwide; 229 participants at 62 study sites in Australia, Israel, Latin America, North America, and Europe (Main Study), and 32 participants at 10 study sites in Japan.

Participants were randomized in a 1:1 ratio double-masked fashion using baseline immunosuppressant (IMM) usage as the stratification factor. Participants in the Japan sub-study were randomized in a separate stratum with no stratification by baseline IMM usage. Study completion is 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, 10 to 35 mg/day at study entry followed by a protocol-defined mandatory taper until Week 19.	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, 10 - 35 mg/day at study entry followed by a protocol-defined mandatory taper until Week 19.
Overall Study STARTED	130	131
Overall Study Enrolled in Main Study	114	115
Overall Study Enrolled in Japan Sub-study	16	16
Overall Study COMPLETED	112	116
Overall Study NOT COMPLETED	18	15

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, 10 to 35 mg/day at study entry followed by a protocol-defined mandatory taper until Week 19.	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, 10 - 35 mg/day at study entry followed by a protocol-defined mandatory taper until Week 19.
Overall Study Miscellaneous	4	2
Overall Study Adverse Event	7	11
Overall Study Lack of Efficacy	2	0
Overall Study Withdrawal by Subject	3	2
Overall Study Lost to Follow-up	2	0

Baseline Characteristics

Efficacy and Safety of Adalimumab in Subjects With Inactive Uveitis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=130 Participants 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, 10 to 35 mg/day at study entry followed by a protocol-defined mandatory taper until Week 19.	Adalimumab n=131 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, 10 - 35 mg/day at study entry followed by a protocol-defined mandatory taper until Week 19.	Total n=261 Participants Total of all reporting groups
Age, Continuous	43.22 years STANDARD_DEVIATION 14.026 • n=5 Participants	43.18 years STANDARD_DEVIATION 12.719 • n=7 Participants	43.20 years STANDARD_DEVIATION 13.360 • n=5 Participants
Age, Customized < 65 years	121 participants n=5 Participants	125 participants n=7 Participants	246 participants n=5 Participants
Age, Customized ≥ 65 years	9 participants n=5 Participants	6 participants n=7 Participants	15 participants n=5 Participants
Sex: Female, Male Female	83 Participants n=5 Participants	75 Participants n=7 Participants	158 Participants n=5 Participants
Sex: Female, Male Male	47 Participants n=5 Participants	56 Participants n=7 Participants	103 Participants n=5 Participants
Race/Ethnicity, Customized White	96 participants n=5 Participants	96 participants n=7 Participants	192 participants n=5 Participants
Race/Ethnicity, Customized Black	8 participants n=5 Participants	6 participants n=7 Participants	14 participants n=5 Participants
Race/Ethnicity, Customized Asian	19 participants n=5 Participants	19 participants n=7 Participants	38 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	9 participants n=7 Participants	14 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	30 participants n=5 Participants	17 participants n=7 Participants	47 participants n=5 Participants
Type of Uveitis Posterior	36 participants n=5 Participants	41 participants n=7 Participants	77 participants n=5 Participants
Type of Uveitis Panuveitis	63 participants n=5 Participants	71 participants n=7 Participants	134 participants n=5 Participants
Type of Uveitis Intermediate/Posterior	1 participants n=5 Participants	2 participants n=7 Participants	3 participants n=5 Participants
Diagnosis Idiopathic	45 participants n=5 Participants	33 participants n=7 Participants	78 participants n=5 Participants
Diagnosis Birdshot Choroidopathy	16 participants n=5 Participants	15 participants n=7 Participants	31 participants n=5 Participants
Diagnosis Multifocal Choroiditis and Panuveitis	2 participants n=5 Participants	5 participants n=7 Participants	7 participants n=5 Participants
Diagnosis Vogt Koyanagi Harada	30 participants n=5 Participants	34 participants n=7 Participants	64 participants n=5 Participants
Diagnosis Sarcoid	20 participants n=5 Participants	22 participants n=7 Participants	42 participants n=5 Participants
Diagnosis Behcet's	7 participants n=5 Participants	10 participants n=7 Participants	17 participants n=5 Participants
Diagnosis Other	10 participants n=5 Participants	12 participants n=7 Participants	22 participants n=5 Participants
Eye Affected Left	3 participants n=5 Participants	3 participants n=7 Participants	6 participants n=5 Participants
Eye Affected Right	5 participants n=5 Participants	2 participants n=7 Participants	7 participants n=5 Participants
Eye Affected Both	122 participants n=5 Participants	126 participants n=7 Participants	248 participants n=5 Participants
History of Infectious Uveitis Yes	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
History of Infectious Uveitis No	130 participants n=5 Participants	131 participants n=7 Participants	261 participants n=5 Participants
Duration of Uveitis	59.36 months STANDARD_DEVIATION 64.753 • n=5 Participants	58.35 months STANDARD_DEVIATION 61.834 • n=7 Participants	58.85 months STANDARD_DEVIATION 63.185 • 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; 3 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: Adalimumab n=115 Participants Participants, excluding those enrolled in the Japan sub-study, 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, 10 - 35 mg/day at study entry followed by a protocol-defined mandatory taper until Week 19.	Integrated Study (Main + Japan Sub-study): Placebo n=127 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, 10 - 35 mg/day at study entry followed by a protocol-defined mandatory taper until Week 19.	Integrated Study (Main + Japan Sub-study): Adalimumab n=131 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 eow starting at Week 1 for a maximum of 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 10 - 35 mg/day at study entry followed by a protocol-defined mandatory taper until Week 19.	Main Study: Placebo n=111 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, 10 - 35 mg/day at study entry followed by a protocol-defined mandatory taper until Week 19.
Time to Treatment Failure on or After Week 2	NA months Interval 4.7 to Not estimable due to the low number of events	5.6 months Interval 2.6 to Not estimable due to the low number of events	NA months Interval 3.9 to Not estimable due to the low number of events	8.3 months Interval 3.0 to Not estimable due to the low number of events

SECONDARY outcome

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

Population: Intent-to-treat population with a Baseline and at least one post-baseline value; last observation carried forward (LOCF) imputation was used.

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: Adalimumab n=115 Participants Participants, excluding those enrolled in the Japan sub-study, 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, 10 - 35 mg/day at study entry followed by a protocol-defined mandatory taper until Week 19.	Integrated Study (Main + Japan Sub-study): Placebo n=126 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, 10 - 35 mg/day at study entry followed by a protocol-defined mandatory taper until Week 19.	Integrated Study (Main + Japan Sub-study): Adalimumab n=131 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 eow starting at Week 1 for a maximum of 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 10 - 35 mg/day at study entry followed by a protocol-defined mandatory taper until Week 19.	Main Study: Placebo n=110 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, 10 - 35 mg/day at study entry followed by a protocol-defined mandatory taper until Week 19.
Change in Anterior Chamber (AC) Cell Grade in Each Eye From Baseline to the Final/Early Termination Visit Left eye	0.41 units on a scale Standard Deviation 0.969	0.61 units on a scale Standard Deviation 1.005	0.46 units on a scale Standard Deviation 0.996	0.57 units on a scale Standard Deviation 1.001
Change in Anterior Chamber (AC) Cell Grade in Each Eye From Baseline to the Final/Early Termination Visit Right eye	0.40 units on a scale Standard Deviation 0.927	0.60 units on a scale Standard Deviation 0.992	0.44 units on a scale Standard Deviation 0.950	0.53 units on a scale Standard Deviation 0.963

SECONDARY outcome

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

Population: Intent-to-treat population with a Baseline and at least one post-baseline value; last observation carried forward (LOCF) imputation was used.

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: Adalimumab n=115 Participants Participants, excluding those enrolled in the Japan sub-study, 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, 10 - 35 mg/day at study entry followed by a protocol-defined mandatory taper until Week 19.	Integrated Study (Main + Japan Sub-study): Placebo n=126 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, 10 - 35 mg/day at study entry followed by a protocol-defined mandatory taper until Week 19.	Integrated Study (Main + Japan Sub-study): Adalimumab n=131 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 eow starting at Week 1 for a maximum of 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 10 - 35 mg/day at study entry followed by a protocol-defined mandatory taper until Week 19.	Main Study: Placebo n=110 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, 10 - 35 mg/day at study entry followed by a protocol-defined mandatory taper until Week 19.
Change in Vitreous Haze (VH) Grade in Each Eye From Baseline to the Final/Early Termination Visit Left eye	0.16 units on a scale Standard Deviation 0.601	0.35 units on a scale Standard Deviation 0.749	0.18 units on a scale Standard Deviation 0.614	0.33 units on a scale Standard Deviation 0.733
Change in Vitreous Haze (VH) Grade in Each Eye From Baseline to the Final/Early Termination Visit Right eye	0.18 units on a scale Standard Deviation 0.604	0.36 units on a scale Standard Deviation 0.729	0.18 units on a scale Standard Deviation 0.602	0.27 units on a scale Standard Deviation 0.605

SECONDARY outcome

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

Population: Intent-to-treat population with a Baseline and at least one post-baseline value; last observation carried forward (LOCF) imputation was used.

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. On the logMAR scale, 0 is equivalent to 20/20 visual acuity, the range of normal vision is considered to be from -0.2 - 0.1; higher values indicate visual impairment.

Outcome measures

Outcome measures
Measure	Main Study: Adalimumab n=115 Participants Participants, excluding those enrolled in the Japan sub-study, 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, 10 - 35 mg/day at study entry followed by a protocol-defined mandatory taper until Week 19.	Integrated Study (Main + Japan Sub-study): Placebo n=126 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, 10 - 35 mg/day at study entry followed by a protocol-defined mandatory taper until Week 19.	Integrated Study (Main + Japan Sub-study): Adalimumab n=131 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 eow starting at Week 1 for a maximum of 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 10 - 35 mg/day at study entry followed by a protocol-defined mandatory taper until Week 19.	Main Study: Placebo n=110 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, 10 - 35 mg/day at study entry followed by a protocol-defined mandatory taper until Week 19.
Change In Logarithm of the Minimum Angle of Resolution (LogMAR) Best Corrected Visual Acuity (BCVA) In Each Eye From Baseline to the Final/Early Termination Visit Left eye	0.01 logMAR Standard Deviation 0.251	0.07 logMAR Standard Deviation 0.230	0.02 logMAR Standard Deviation 0.241	0.06 logMAR Standard Deviation 0.239
Change In Logarithm of the Minimum Angle of Resolution (LogMAR) Best Corrected Visual Acuity (BCVA) In Each Eye From Baseline to the Final/Early Termination Visit Right eye	-0.01 logMAR Standard Deviation 0.165	0.04 logMAR Standard Deviation 0.216	0.00 logMAR Standard Deviation 0.169	0.02 logMAR Standard Deviation 0.198

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 2 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: Adalimumab n=90 Participants Participants, excluding those enrolled in the Japan sub-study, 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, 10 - 35 mg/day at study entry followed by a protocol-defined mandatory taper until Week 19.	Integrated Study (Main + Japan Sub-study): Placebo n=106 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, 10 - 35 mg/day at study entry followed by a protocol-defined mandatory taper until Week 19.	Integrated Study (Main + Japan Sub-study): Adalimumab n=102 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 eow starting at Week 1 for a maximum of 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 10 - 35 mg/day at study entry followed by a protocol-defined mandatory taper until Week 19.	Main Study: Placebo n=95 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, 10 - 35 mg/day at study entry followed by a protocol-defined mandatory taper until Week 19.
Time to Optimal Coherence Tomography (OCT) Evidence of Macular Edema in At Least 1 Eye On or After Week 2	NA months Could not be estimated due to the low number of events	NA months Could not be estimated due to the low number of events	NA months Could not be estimated due to the low number of events	NA months Could not be estimated due to the low number of events

SECONDARY outcome

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

Population: Intent-to-treat population with a Baseline and at least one post-baseline value; last observation carried forward (LOCF) imputation was used.

Central retinal thickness was measured using OCT and assessed by a central reader.

Outcome measures

Outcome measures
Measure	Main Study: Adalimumab n=114 Participants Participants, excluding those enrolled in the Japan sub-study, 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, 10 - 35 mg/day at study entry followed by a protocol-defined mandatory taper until Week 19.	Integrated Study (Main + Japan Sub-study): Placebo n=124 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, 10 - 35 mg/day at study entry followed by a protocol-defined mandatory taper until Week 19.	Integrated Study (Main + Japan Sub-study): Adalimumab n=130 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 eow starting at Week 1 for a maximum of 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 10 - 35 mg/day at study entry followed by a protocol-defined mandatory taper until Week 19.	Main Study: Placebo n=108 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, 10 - 35 mg/day at study entry followed by a protocol-defined mandatory taper until Week 19.
Percent Change in Central Retinal Thickness in Each Eye From Baseline to the Final/Early Termination Visit. Left eye (N = 107, 114, 122, 130)	4.5 percent change Standard Deviation 29.82	6.3 percent change Standard Deviation 19.75	5.2 percent change Standard Deviation 29.91	6.4 percent change Standard Deviation 20.67
Percent Change in Central Retinal Thickness in Each Eye From Baseline to the Final/Early Termination Visit. Right eye (N = 108, 113, 124, 129)	5.4 percent change Standard Deviation 34.83	9.9 percent change Standard Deviation 30.79	3.9 percent change Standard Deviation 33.34	7.7 percent change Standard Deviation 28.88

SECONDARY outcome

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

Population: Intent-to-treat population with a Baseline and at least one post-baseline value; last observation carried forward (LOCF) imputation was used.

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: Adalimumab n=115 Participants Participants, excluding those enrolled in the Japan sub-study, 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, 10 - 35 mg/day at study entry followed by a protocol-defined mandatory taper until Week 19.	Integrated Study (Main + Japan Sub-study): Placebo n=125 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, 10 - 35 mg/day at study entry followed by a protocol-defined mandatory taper until Week 19.	Integrated Study (Main + Japan Sub-study): Adalimumab n=131 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 eow starting at Week 1 for a maximum of 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 10 - 35 mg/day at study entry followed by a protocol-defined mandatory taper until Week 19.	Main Study: Placebo n=109 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, 10 - 35 mg/day at study entry followed by a protocol-defined mandatory taper until Week 19.
Change in Visual Functioning Questionnaire 25 (VFQ-25) Total Score From Baseline to the Final/Early Termination Visit	3.36 units on a scale Standard Deviation 11.73	1.00 units on a scale Standard Deviation 10.225	2.79 units on a scale Standard Deviation 12.018	1.24 units on a scale Standard Deviation 10.698

SECONDARY outcome

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

Population: Intent-to-treat population with a Baseline and at least one post-baseline value; last observation carried forward (LOCF) imputation was used.

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: Adalimumab n=115 Participants Participants, excluding those enrolled in the Japan sub-study, 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, 10 - 35 mg/day at study entry followed by a protocol-defined mandatory taper until Week 19.	Integrated Study (Main + Japan Sub-study): Placebo n=125 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, 10 - 35 mg/day at study entry followed by a protocol-defined mandatory taper until Week 19.	Integrated Study (Main + Japan Sub-study): Adalimumab n=131 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 eow starting at Week 1 for a maximum of 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 10 - 35 mg/day at study entry followed by a protocol-defined mandatory taper until Week 19.	Main Study: Placebo n=109 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, 10 - 35 mg/day at study entry followed by a protocol-defined mandatory taper until Week 19.
Change in VFQ-25 Subscore Distance Vision From Baseline to the Final/Early Termination Visit	2.64 units on a scale Standard Deviation 17.165	0.60 units on a scale Standard Deviation 15.978	2.96 units on a scale Standard Deviation 17.121	0.76 units on a scale Standard Deviation 16.248

SECONDARY outcome

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

Population: Intent-to-treat population with a Baseline and at least one post-baseline value; last observation carried forward (LOCF) imputation was used.

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 near 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: Adalimumab n=115 Participants Participants, excluding those enrolled in the Japan sub-study, 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, 10 - 35 mg/day at study entry followed by a protocol-defined mandatory taper until Week 19.	Integrated Study (Main + Japan Sub-study): Placebo n=125 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, 10 - 35 mg/day at study entry followed by a protocol-defined mandatory taper until Week 19.	Integrated Study (Main + Japan Sub-study): Adalimumab n=131 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 eow starting at Week 1 for a maximum of 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 10 - 35 mg/day at study entry followed by a protocol-defined mandatory taper until Week 19.	Main Study: Placebo n=109 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, 10 - 35 mg/day at study entry followed by a protocol-defined mandatory taper until Week 19.
Change in VFQ-25 Subscore Near Vision From Baseline to the Final/Early Termination Visit	3.88 units on a scale Standard Deviation 18.302	3.73 units on a scale Standard Deviation 17.17	2.89 units on a scale Standard Deviation 50.503	3.98 units on a scale Standard Deviation 17.397

SECONDARY outcome

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

Population: Intent-to-treat population with a Baseline and at least one post-baseline value; last observation carried forward (LOCF) imputation was used.

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 form the answers to 2 eye pain questions and ranges from 0 to 100, where higher scores or increases in score indicate less pain.

Outcome measures

Outcome measures
Measure	Main Study: Adalimumab n=115 Participants Participants, excluding those enrolled in the Japan sub-study, 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, 10 - 35 mg/day at study entry followed by a protocol-defined mandatory taper until Week 19.	Integrated Study (Main + Japan Sub-study): Placebo n=125 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, 10 - 35 mg/day at study entry followed by a protocol-defined mandatory taper until Week 19.	Integrated Study (Main + Japan Sub-study): Adalimumab n=131 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 eow starting at Week 1 for a maximum of 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 10 - 35 mg/day at study entry followed by a protocol-defined mandatory taper until Week 19.	Main Study: Placebo n=109 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, 10 - 35 mg/day at study entry followed by a protocol-defined mandatory taper until Week 19.
Change in VFQ-25 Subscore Ocular Pain From Baseline to the Final/Early Termination Visit	3.42 units on a scale Standard Deviation 21.32	2.60 units on a scale Standard Deviation 17.339	2.15 units on a scale Standard Deviation 21.689	2.87 units on a scale Standard Deviation 17.233

Adverse Events

Placebo

Serious events: 10 serious events

Other events: 78 other events

Deaths: 0 deaths

Adalimumab

Serious events: 8 serious events

Other events: 88 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=130 participants at risk 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, 10 to 35 mg/day at study entry followed by a protocol-defined mandatory taper until Week 19.	Adalimumab n=131 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, 10 - 35 mg/day at study entry followed by a protocol-defined mandatory taper until Week 19.
Blood and lymphatic system disorders NEUTROPENIA	0.00% 0/130 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.	0.76% 1/131 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.
Cardiac disorders CARDIAC TAMPONADE	0.00% 0/130 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.	0.76% 1/131 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.
Eye disorders BLINDNESS TRANSIENT	0.00% 0/130 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.	0.76% 1/131 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.
Eye disorders CHOROIDAL NEOVASCULARISATION	0.77% 1/130 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.	0.00% 0/131 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.
Eye disorders RETINAL DETACHMENT	0.77% 1/130 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.	0.00% 0/131 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.
Eye disorders SUBRETINAL FLUID	0.77% 1/130 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.	0.00% 0/131 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.
Gastrointestinal disorders DYSPHAGIA	0.00% 0/130 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.	0.76% 1/131 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.
Infections and infestations BRONCHITIS	0.00% 0/130 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.	0.76% 1/131 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.
Infections and infestations MENINGITIS ASEPTIC	0.77% 1/130 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.	0.00% 0/131 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.
Infections and infestations PNEUMONIA	0.00% 0/130 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.	0.76% 1/131 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.
Infections and infestations PNEUMONIA LEGIONELLA	0.00% 0/130 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.	0.76% 1/131 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.
Infections and infestations TONSILLITIS	0.77% 1/130 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.	0.00% 0/131 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.
Injury, poisoning and procedural complications FIBULA FRACTURE	0.00% 0/130 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.	0.76% 1/131 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.
Injury, poisoning and procedural complications HUMERUS FRACTURE	0.77% 1/130 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.	0.00% 0/131 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.
Musculoskeletal and connective tissue disorders ARTHRITIS	0.77% 1/130 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.	0.00% 0/131 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.
Musculoskeletal and connective tissue disorders OSTEONECROSIS	0.77% 1/130 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.	0.00% 0/131 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) LUNG ADENOCARCINOMA STAGE IV	0.00% 0/130 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.	0.76% 1/131 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.
Nervous system disorders DYSARTHRIA	0.00% 0/130 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.	0.76% 1/131 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.
Nervous system disorders STATUS MIGRAINOSUS	0.00% 0/130 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.	0.76% 1/131 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.
Respiratory, thoracic and mediastinal disorders EPISTAXIS	0.00% 0/130 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.	0.76% 1/131 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.
Respiratory, thoracic and mediastinal disorders PLEURISY	0.00% 0/130 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.	0.76% 1/131 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.
Vascular disorders AORTIC DISSECTION	0.00% 0/130 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.	0.76% 1/131 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.
Vascular disorders DEEP VEIN THROMBOSIS	1.5% 2/130 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.	0.00% 0/131 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.
Vascular disorders HYPERTENSIVE CRISIS	0.77% 1/130 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.	0.00% 0/131 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.

Measure	Placebo n=130 participants at risk 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, 10 to 35 mg/day at study entry followed by a protocol-defined mandatory taper until Week 19.	Adalimumab n=131 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, 10 - 35 mg/day at study entry followed by a protocol-defined mandatory taper until Week 19.
Eye disorders CYSTOID MACULAR OEDEMA	5.4% 7/130 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.	5.3% 7/131 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.
Eye disorders DRY EYE	6.2% 8/130 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.	3.8% 5/131 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.
Eye disorders EYE PAIN	4.6% 6/130 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.	6.9% 9/131 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.
Eye disorders UVEITIS	6.9% 9/130 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.	4.6% 6/131 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.
Eye disorders VISUAL ACUITY REDUCED	7.7% 10/130 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.	4.6% 6/131 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.
Gastrointestinal disorders DIARRHOEA	6.9% 9/130 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.	3.1% 4/131 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.
Gastrointestinal disorders NAUSEA	6.9% 9/130 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.	3.1% 4/131 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.
General disorders FATIGUE	6.9% 9/130 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.	10.7% 14/131 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.
General disorders INJECTION SITE PAIN	6.9% 9/130 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.	6.1% 8/131 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.
General disorders PYREXIA	6.2% 8/130 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.	4.6% 6/131 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.
Infections and infestations INFLUENZA	5.4% 7/130 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.	2.3% 3/131 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.
Infections and infestations NASOPHARYNGITIS	15.4% 20/130 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.	17.6% 23/131 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.
Infections and infestations SINUSITIS	3.1% 4/130 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.	6.1% 8/131 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.
Infections and infestations UPPER RESPIRATORY TRACT INFECTION	2.3% 3/130 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.	7.6% 10/131 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.
Infections and infestations URINARY TRACT INFECTION	8.5% 11/130 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.	9.9% 13/131 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.
Investigations ALANINE AMINOTRANSFERASE INCREASED	0.77% 1/130 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.	6.9% 9/131 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.
Investigations ASPARTATE AMINOTRANSFERASE INCREASED	0.77% 1/130 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.	6.1% 8/131 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.
Musculoskeletal and connective tissue disorders ARTHRALGIA	9.2% 12/130 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.	21.4% 28/131 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.
Musculoskeletal and connective tissue disorders BACK PAIN	5.4% 7/130 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.	7.6% 10/131 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.
Musculoskeletal and connective tissue disorders PAIN IN EXTREMITY	2.3% 3/130 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.	7.6% 10/131 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.
Nervous system disorders HEADACHE	13.1% 17/130 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.	13.0% 17/131 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.
Psychiatric disorders INSOMNIA	2.3% 3/130 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.	6.9% 9/131 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.
Respiratory, thoracic and mediastinal disorders COUGH	4.6% 6/130 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.	8.4% 11/131 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.
Vascular disorders HYPERTENSION	3.8% 5/130 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.	5.3% 7/131 • 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 147 days in the placebo arm and 245 days in the adalimumab arm.