Visual II: Efficacy and Safety of Adalimumab in Subjects With Inactive Uveitis

• Sponsor: AbbVie (prior sponsor, Abbott) (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01124838
• Collaborator: (none)
• Enrollment: 261
• Arms: 2
• Duration (Months): 57

Study Details

Study Description

Brief Summary

A study comparing the safety and efficacy of adalimumab compared with. placebo in adults with inactive non-infectious intermediate uveitis, posterior uveitis, or panuveitis.

Condition or Disease	Intervention/Treatment	Phase
Uveitis	Drug: Adalimumab; Drug: Prednisone; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 261 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multicenter Study of the Efficacy and Safety of the Human Anti-TNF Monoclonal Antibody Adalimumab in Subjects With Inactive Non-infectious Intermediate Uveitis, Posterior Uveitis, or Panuveitis - Including a Sub-study in Japanese Patients
• Study Start Date: Aug 1, 2010
• Actual Primary Completion Date: May 1, 2015
• Actual Study Completion Date: May 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: 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.	Drug: Prednisone; Administered orally, 10 - 35 mg/day at study entry followed by a protocol-defined mandatory taper schedule in which all subjects continuing in the study were to discontinue prednisone no later than Week 19.; Drug: Placebo; Administered by subcutaneous injection
Experimental: 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.	Drug: Adalimumab; Administered subcutaneously as an 80 mg loading dose (2 syringes) at Baseline followed by 40 mg eow starting at Week 1.; Other Names: ABT-D2E7 Humira ; Drug: Prednisone; Administered orally, 10 - 35 mg/day at study entry followed by a protocol-defined mandatory taper schedule in which all subjects continuing in the study were to discontinue prednisone no later than Week 19.

Outcome Measures

Primary Outcome Measures

1. Time to Treatment Failure on or After Week 2 [From Baseline until end of study (up to 80 weeks)]

   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.

Secondary Outcome Measures

1. Change in Anterior Chamber (AC) Cell Grade in Each Eye From Baseline to the Final/Early Termination Visit [Baseline and at the Final/Early Termination Visit (up to 80 weeks)]

   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.

2. Change in Vitreous Haze (VH) Grade in Each Eye From Baseline to the Final/Early Termination Visit [Baseline and Final/Early Termination Visit (up to 80 weeks)]

   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.

3. 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 [Baseline and Final/Early Termination Visit (up to 80 weeks)]

   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.

4. Time to Optimal Coherence Tomography (OCT) Evidence of Macular Edema in At Least 1 Eye On or After Week 2 [From Baseline until the Final Visit (up to 80 weeks)]

   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.

5. Percent Change in Central Retinal Thickness in Each Eye From Baseline to the Final/Early Termination Visit. [Baseline and Final/Early Termination Visit (up to 80 weeks)]

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

6. Change in Visual Functioning Questionnaire 25 (VFQ-25) Total Score From Baseline to the Final/Early Termination Visit [Baseline and Final/Early Termination Visit (up 80 weeks)]

   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.

7. Change in VFQ-25 Subscore Distance Vision From Baseline to the Final/Early Termination Visit [Baseline and Final/Early Termination Visit (up 80 weeks)]

   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.

8. Change in VFQ-25 Subscore Near Vision From Baseline to the Final/Early Termination Visit [Baseline and Final/Early Termination Visit (up 80 weeks)]

   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.

9. Change in VFQ-25 Subscore Ocular Pain From Baseline to the Final/Early Termination Visit [Baseline and Final/Early Termination Visit (up 80 weeks)]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 99 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subject is diagnosed with non-infectious intermediate, posterior, or panuveitis.

• Subject that for ≥ 28 days prior to the Baseline visit has inactive disease and is taking ≥ 10 mg of oral prednisone to maintain this inactive state and fulfillment of all 3 of the following criteria based on the Investigator's clinical judgment at the

Screening and Baseline visits for both eyes:

• Subject without active, inflammatory chorioretinal and/or inflammatory retinal vascular lesions.

• Subject with anterior chamber cell grade ≤ 0.5+ according to Standardization of Uveitis Nomenclature (SUN) criteria.

• Subject with vitreous haze grade ≤ 0.5+ according to National Eye Institute (NEI)/SUN criteria.

• Subject is on oral prednisone 10 to 35 mg/day (or oral corticosteroid equivalent) at Baseline and the dose has not been increased in the past 28 days or decreased in the past 14 days.

• Subject must have a documented history of experiencing at least one disease flare within 18 months of the Screening visit. This flare has to occur during or up to a maximum of 28 days after tapering off the oral corticosteroid therapy.

• Subjects who do not have previous, active or latent tuberculosis (TB). Only one TB test is required to allow the subject in the study. Subjects with either negative purified protein derivative (PPD) (< 5 mm of induration) or negative QuantiFERON®-TB Gold test (or interferon-gamma release assay (IGRA) equivalent) are eligible. Subjects with a repeat indeterminate QuantiFERON®-TB Gold test (or IGRA equivalent) result are not eligible. Note, that only one TB screening test is allowed and required. A repeat QuantiFERON®-TB Gold test (or IGRA equivalent) is not permitted if the PPD skin test is positive. The TB screening tests are diagnostic tests. In the event of a negative TB screening test, the results are to be interpreted in the context of the patient's epidemiology, history, exam findings, etc. and it is the responsibility of the investigator to determine if a patient has previous, active or latent tuberculosis or not. Under no circumstances can a patient with a positive PPD result or positive QuantiFERON®-TB Gold test (or IGRA equivalent) enter the study.

Exclusion Criteria:

• Subject with isolated anterior uveitis.

• Subject with confirmed or suspected infectious uveitis, including but not limited to infectious uveitis due to TB, cytomegalovirus (CMV), Lyme disease, toxoplasmosis, human T-lymphotropic virus type 1 (HTLV-1) infection, Whipple's disease, herpes zoster virus (HZV) and herpes simplex virus (HSV).

• Subject with serpiginous choroidopathy.

• Subject with corneal or lens opacity that precludes visualization of the fundus or that likely requires cataract surgery during the duration of the trial.

• Subject with intraocular pressure of ≥ 25 mmHg and on ≥ 2 glaucoma medications or evidence of glaucomatous optic nerve injury.

• Subject with best corrected visual acuity (BCVA) less than 20 letters (ETDRS [Early Treatment Diabetic Retinopathy Study]) in at least one eye at the Baseline visit.

• Subject with intermediate uveitis or panuveitis that has signs of intermediate uveitis (e.g. presence or history of snowbanking or snowballs) and symptoms and/or magnetic resonance imaging (MRI) findings suggestive of a demyelinating disease such as multiple sclerosis. All subjects with intermediate uveitis or panuveitis that have signs of intermediate uveitis (e.g. presence or history of snowbanking or snowballs) must have a brain MRI within 90 days prior to the Baseline visit.

• Subject has previous exposure to anti-tumor necrosis factor (TNF) therapy or any biologic therapy (except intravitreal anti- vascular endothelial growth factor (VEGF) therapy) with a potential therapeutic impact on non-infectious uveitis.

• Subject on concomitant immunosuppressive therapy other than methotrexate, cyclosporine, mycophenolate mofetil or an equivalent drug to mycophenolate mofetil (e.g., mycophenolic acid), azathioprine or tacrolimus within 28 days of Baseline or has discontinued an immunosuppressive therapy including methotrexate, cyclosporine, mycophenolate mofetil or an equivalent drug to mycophenolate mofetil (e.g., mycophenolic acid), azathioprine or tacrolimus within 28 days of Baseline.

• If entering the study on one concomitant immunosuppressive therapy, dose has not been stable for at least 28 days prior to the Baseline visit or is not within the following allowable doses at the Baseline visit:

• Methotrexate (MTX) ≤ 25 mg per week

• Cyclosporine ≤ 4 mg/kg per day

• Mycophenolate mofetil ≤ 2 grams per day or an equivalent drug to mycophenolate mofetil (e.g. mycophenolic acid) at an equivalent dose approved by the Medical Monitor

• Azathioprine ≤ 175 mg per day

• Tacrolimus (oral formulation) ≤ 8 mg per day

• Subject has Retisert® (glucocorticosteroids implant) within 3 years prior to the Baseline visit or has had complications related to the device. Subject has had Retisert® (glucocorticosteroid implant) removed within 90 days prior to the Baseline visit or has had complications related to removal of the device.

• Subject has received intraocular or periocular corticosteroids within 90 days prior to the Baseline visit.

• Subject with proliferative or severe non-proliferative diabetic retinopathy or clinically significant macular edema due to diabetic retinopathy.

• Subject with neovascular/wet age-related macular degeneration.

• Subject with abnormality of vitreo-retinal interface (i.e., vitreomacular traction, epiretinal membranes, etc.) with the potential for macular structural damage independent of the inflammatory process.

• Subject with cystoid macular edema unless the retinal changes are persistent, residual and stable as defined by the SUN criteria (persistent is > 3 months duration).

• Subject has received Ozurdex® (dexamethasone implant) within 6 months prior to the Baseline visit.

• Subject has received intravitreal methotrexate within 90 days prior to the Baseline visit.

• Subject has received intravitreal anti-VEGF therapy:

• within 45 days of the Baseline visit for Lucentis® (ranibizumab) or Avastin® (bevacizumab);

• or within 60 days of the Baseline visit for anti-VEGF Trap (Aflibercept).

• Subject on systemic carbonic anhydrase inhibitor within 1 week prior to Screening visit.

• Subject with a history of scleritis.

• Subject on cyclophosphamide within 30 days prior to the Baseline visit.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• AbbVie (prior sponsor, Abbott)

Investigators

• Study Director: Andy Payne, AbbVie

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• This clinical study may be evaluating a usage that is not currently FDA-approved. Please see US Prescribing Information for approved uses.

Publications

• Nguyen QD, Merrill PT, Jaffe GJ, Dick AD, Kurup SK, Sheppard J, Schlaen A, Pavesio C, Cimino L, Van Calster J, Camez AA, Kwatra NV, Song AP, Kron M, Tari S, Brézin AP. Adalimumab for prevention of uveitic flare in patients with inactive non-infectious uveitis controlled by corticosteroids (VISUAL II): a multicentre, double-masked, randomised, placebo-controlled phase 3 trial. Lancet. 2016 Sep 17;388(10050):1183-92. doi: 10.1016/S0140-6736(16)31339-3. Epub 2016 Aug 16. Erratum in: Lancet. 2016 Sep 17;388(10050):1160.

• Responsible Party: AbbVie (prior sponsor, Abbott)
• ClinicalTrials.gov Identifier: NCT01124838
• Other Study ID Numbers: M10-880; 2009-016008-22
• First Posted: May 17, 2010
• Last Update Posted: Jul 7, 2021
• Last Verified: Jul 1, 2021

• Keywords provided by AbbVie (prior sponsor, Abbott): Uveitis
• Additional relevant MeSH terms: Uveitis; Prednisone; Adalimumab

Study Results

Participant Flow

Recruitment Details	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.
Pre-assignment Detail	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.

Arm/Group Title	Placebo	Adalimumab
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	130	131
Enrolled in Main Study	114	115
Enrolled in Japan Sub-study	16	16
COMPLETED	112	116
NOT COMPLETED	18	15

Baseline Characteristics

Arm/Group Title	Placebo	Adalimumab	Total
Arm/Group Description	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.	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 of all reporting groups
Overall Participants	130	131	261
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	43.22 (14.026)	43.18 (12.719)	43.20 (13.360)
Age, Customized (participants) [Number]
< 65 years	121 93.1%	125 95.4%	246 94.3%
≥ 65 years	9 6.9%	6 4.6%	15 5.7%
Sex: Female, Male (Count of Participants)
Female	83 63.8%	75 57.3%	158 60.5%
Male	47 36.2%	56 42.7%	103 39.5%
Race/Ethnicity, Customized (participants) [Number]
White	96 73.8%	96 73.3%	192 73.6%
Black	8 6.2%	6 4.6%	14 5.4%
Asian	19 14.6%	19 14.5%	38 14.6%
American Indian/Alaskan Native	1 0.8%	0 0%	1 0.4%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Other	5 3.8%	9 6.9%	14 5.4%
Multi-Race	1 0.8%	1 0.8%	2 0.8%
Type of Uveitis (participants) [Number]
Intermediate	30 23.1%	17 13%	47 18%
Posterior	36 27.7%	41 31.3%	77 29.5%
Panuveitis	63 48.5%	71 54.2%	134 51.3%
Intermediate/Posterior	1 0.8%	2 1.5%	3 1.1%
Diagnosis (participants) [Number]
Idiopathic	45 34.6%	33 25.2%	78 29.9%
Birdshot Choroidopathy	16 12.3%	15 11.5%	31 11.9%
Multifocal Choroiditis and Panuveitis	2 1.5%	5 3.8%	7 2.7%
Vogt Koyanagi Harada	30 23.1%	34 26%	64 24.5%
Sarcoid	20 15.4%	22 16.8%	42 16.1%
Behcet's	7 5.4%	10 7.6%	17 6.5%
Other	10 7.7%	12 9.2%	22 8.4%
Eye Affected (participants) [Number]
Left	3 2.3%	3 2.3%	6 2.3%
Right	5 3.8%	2 1.5%	7 2.7%
Both	122 93.8%	126 96.2%	248 95%
History of Infectious Uveitis (participants) [Number]
Yes	0 0%	0 0%	0 0%
No	130 100%	131 100%	261 100%
Duration of Uveitis (months) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [months]	59.36 (64.753)	58.35 (61.834)	58.85 (63.185)

Outcome Measures

1. Primary Outcome

Title	Time to Treatment Failure on or After Week 2
Description	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.
Time Frame	From Baseline until end of study (up to 80 weeks)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Main Study: Placebo	Main Study: Adalimumab	Integrated Study (Main + Japan Sub-study): Placebo	Integrated Study (Main + Japan Sub-study): Adalimumab
Arm/Group Description	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.	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.	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.	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.
Measure Participants	111	115	127	131
Median (Inter-Quartile Range) [months]	8.3	NA	5.6	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Main Study: Placebo, Main Study: Adalimumab
	Comments	The primary analysis of the primary endpoint was performed on Main Study data, excluding the Japanese sub-study. The statistical test was performed at a 2-sided significance level of 0.05. The hazard ratio of adalimumab versus placebo was calculated using proportional hazards regression with treatment as factor.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.004
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.57
	Confidence Interval	(2-Sided) 95%; 0.39 to 0.84
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Integrated Study (Main + Japan Sub-study): Placebo, Integrated Study (Main + Japan Sub-study): Adalimumab
	Comments	An additional analysis of the primary endpoint was performed using the Integrated Study data (Main Study + Japan sub-study). The statistical test was performed at a 2-sided significance level of 0.05. The hazard ratio of adalimumab versus placebo was calculated using proportional hazards regression with treatment and race (Japanese versus non-Japanese) as factors.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.52
	Confidence Interval	(2-Sided) 95%; 0.37 to 0.74
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change in Anterior Chamber (AC) Cell Grade in Each Eye From Baseline to the Final/Early Termination Visit
Description	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.
Time Frame	Baseline and at the Final/Early Termination Visit (up to 80 weeks)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Main Study: Placebo	Main Study: Adalimumab	Integrated Study (Main + Japan Sub-study): Placebo	Integrated Study (Main + Japan Sub-study): Adalimumab
Arm/Group Description	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.	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.	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.	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.
Measure Participants	110	115	126	131
Left eye	0.57 (1.001)	0.41 (0.969)	0.61 (1.005)	0.46 (0.996)
Right eye	0.53 (0.963)	0.40 (0.927)	0.60 (0.992)	0.44 (0.950)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Main Study: Placebo, Main Study: Adalimumab
	Comments	The statistical test for the ranked secondary variables was carried out in hierarchical order at the significance level of 5%.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.218
	Comments
	Method	ANOVA
	Comments	From ANOVA with treatment as factor adjusted for clustered observations (i.e., observations from each of the participant's eyes).
Method of Estimation	Estimation Parameter	Mean Difference
	Estimated Value	-0.14
	Confidence Interval	(2-Sided) 95%; -0.37 to 0.08
	Parameter Dispersion	Type: Value:
	Estimation Comments	The mean difference between treatment groups with its 95% confidence interval is based on individual data from all eyes adjusted for correlated measurements within a subject in an analysis of variance (ANOVA) model.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Integrated Study (Main + Japan Sub-study): Placebo, Integrated Study (Main + Japan Sub-study): Adalimumab
	Comments	The statistical test for the ranked secondary variables was carried out in hierarchical order at the significance level of 5%.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.164
	Comments
	Method	ANOVA
	Comments	From ANOVA with treatment and race (Japanese versus non-Japanese) as factors adjusted for clustered observations.
Method of Estimation	Estimation Parameter	Mean Difference
	Estimated Value	-0.15
	Confidence Interval	(2-Sided) 95%; -0.36 to 0.06
	Parameter Dispersion	Type: Value:
	Estimation Comments	The mean difference between treatment groups with its 95% confidence interval is based on individual data from all eyes adjusted for correlated measurements within a subject in an analysis of variance (ANOVA) model.

3. Secondary Outcome

Title	Change in Vitreous Haze (VH) Grade in Each Eye From Baseline to the Final/Early Termination Visit
Description	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.
Time Frame	Baseline and Final/Early Termination Visit (up to 80 weeks)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Main Study: Placebo	Main Study: Adalimumab	Integrated Study (Main + Japan Sub-study): Placebo	Integrated Study (Main + Japan Sub-study): Adalimumab
Arm/Group Description	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.	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.	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.	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.
Measure Participants	110	115	126	131
Left eye	0.33 (0.733)	0.16 (0.601)	0.35 (0.749)	0.18 (0.614)
Right eye	0.27 (0.605)	0.18 (0.604)	0.36 (0.729)	0.18 (0.602)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Main Study: Placebo, Main Study: Adalimumab
	Comments	The statistical test for the ranked secondary variables was carried out in hierarchical order at the significance level of 5%.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.070
	Comments
	Method	ANOVA
	Comments	From ANOVA of change from baseline to final/early termination visit with treatment as factor
Method of Estimation	Estimation Parameter	Mean Difference
	Estimated Value	-0.13
	Confidence Interval	(2-Sided) 95%; -0.28 to 0.01
	Parameter Dispersion	Type: Value:
	Estimation Comments	The mean difference between treatment groups with its 95% confidence interval is based on individual data from all eyes adjusted for correlated measurements within a subject in an analysis of variance (ANOVA) model.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Integrated Study (Main + Japan Sub-study): Placebo, Integrated Study (Main + Japan Sub-study): Adalimumab
	Comments	The statistical test for the ranked secondary variables was carried out in hierarchical order at the significance level of 5%.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.016
	Comments
	Method	ANOVA
	Comments	From ANOVA with treatment and race (Japanese versus non-Japanese) as factors adjusted for clustered observations.
Method of Estimation	Estimation Parameter	Mean Difference
	Estimated Value	-0.17
	Confidence Interval	(2-Sided) 95%; -0.31 to -0.03
	Parameter Dispersion	Type: Value:
	Estimation Comments	The mean difference between treatment groups with its 95% confidence interval is based on individual data from all eyes adjusted for correlated measurements within a subject in an analysis of variance (ANOVA) model.

4. Secondary Outcome

Title	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
Description	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.
Time Frame	Baseline and Final/Early Termination Visit (up to 80 weeks)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Main Study: Placebo	Main Study: Adalimumab	Integrated Study (Main + Japan Sub-study): Placebo	Integrated Study (Main + Japan Sub-study): Adalimumab
Arm/Group Description	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.	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.	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.	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.
Measure Participants	110	115	126	131
Left eye	0.06 (0.239)	0.01 (0.251)	0.07 (0.230)	0.02 (0.241)
Right eye	0.02 (0.198)	-0.01 (0.165)	0.04 (0.216)	0.00 (0.169)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Main Study: Placebo, Main Study: Adalimumab
	Comments	The statistical test for the ranked secondary variables was carried out in hierarchical order at the significance level of 5%.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.096
	Comments
	Method	ANOVA
	Comments	From ANOVA of change from baseline to final/early termination visit with treatment as factor adjusted for clustered observations.
Method of Estimation	Estimation Parameter	Mean Difference
	Estimated Value	-0.04
	Confidence Interval	(2-Sided) 95%; -0.08 to 0.01
	Parameter Dispersion	Type: Value:
	Estimation Comments	The mean difference between treatment groups with its 95% confidence interval is based on individual data from all eyes adjusted for correlated measurements within a subject in an analysis of variance (ANOVA) model.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Integrated Study (Main + Japan Sub-study): Placebo, Integrated Study (Main + Japan Sub-study): Adalimumab
	Comments	The statistical test for the ranked secondary variables was carried out in hierarchical order at the significance level of 5%.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.044
	Comments
	Method	ANOVA
	Comments	From ANOVA with treatment and race (Japanese versus non-Japanese) as factors adjusted for clustered observations.
Method of Estimation	Estimation Parameter	Mean Difference
	Estimated Value	-0.04
	Confidence Interval	(2-Sided) 95%; -0.09 to 0.00
	Parameter Dispersion	Type: Value:
	Estimation Comments	The mean difference between treatment groups with its 95% confidence interval is based on individual data from all eyes adjusted for correlated measurements within a subject in an analysis of variance (ANOVA) model.

5. Secondary Outcome

Title	Time to Optimal Coherence Tomography (OCT) Evidence of Macular Edema in At Least 1 Eye On or After Week 2
Description	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.
Time Frame	From Baseline until the Final Visit (up to 80 weeks)

Outcome Measure Data

Analysis Population Description

Intent to treat population with no macular edema at Baseline

Arm/Group Title	Main Study: Placebo	Main Study: Adalimumab	Integrated Study (Main + Japan Sub-study): Placebo	Integrated Study (Main + Japan Sub-study): Adalimumab
Arm/Group Description	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.	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.	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.	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.
Measure Participants	95	90	106	102
Median (Inter-Quartile Range) [months]	NA	NA	NA	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Main Study: Placebo, Main Study: Adalimumab
	Comments	The statistical test for the ranked secondary variables was carried out in hierarchical order at the significance level of 5%.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.491
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.75
	Confidence Interval	(2-Sided) 95%; 0.34 to 1.69
	Parameter Dispersion	Type: Value:
	Estimation Comments	The hazard ratio of adalimumab versus placebo was calculated using proportional hazards regression with treatment as factor.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Integrated Study (Main + Japan Sub-study): Placebo, Integrated Study (Main + Japan Sub-study): Adalimumab
	Comments	The statistical test for the ranked secondary variables was carried out in hierarchical order at the significance level of 5%.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.185
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.60
	Confidence Interval	(2-Sided) 95%; 0.28 to 1.28
	Parameter Dispersion	Type: Value:
	Estimation Comments	The hazard ratio of adalimumab versus placebo was calculated using proportional hazards regression with treatment and race (Japanese versus non-Japanese) as factors.

6. Secondary Outcome

Title	Percent Change in Central Retinal Thickness in Each Eye From Baseline to the Final/Early Termination Visit.
Description	Central retinal thickness was measured using OCT and assessed by a central reader.
Time Frame	Baseline and Final/Early Termination Visit (up to 80 weeks)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Main Study: Placebo	Main Study: Adalimumab	Integrated Study (Main + Japan Sub-study): Placebo	Integrated Study (Main + Japan Sub-study): Adalimumab
Arm/Group Description	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.	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.	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.	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.
Measure Participants	108	114	124	130
Left eye (N = 107, 114, 122, 130)	6.4 (20.67)	4.5 (29.82)	6.3 (19.75)	5.2 (29.91)
Right eye (N = 108, 113, 124, 129)	7.7 (28.88)	5.4 (34.83)	9.9 (30.79)	3.9 (33.34)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Main Study: Placebo, Main Study: Adalimumab
	Comments	The statistical test for the ranked secondary variables was carried out in hierarchical order at the significance level of 5%.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.451
	Comments
	Method	ANOVA
	Comments	From ANOVA of change from baseline to final/early termination visit with treatment and OCT machine as factors adjusted for clustered observations.
Method of Estimation	Estimation Parameter	Mean Difference
	Estimated Value	-2.3
	Confidence Interval	(2-Sided) 95%; -8.5 to 3.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	The mean difference between treatment groups with its 95% confidence interval is based on individual data from all eyes adjusted for correlated measurements within a subject in an analysis of variance (ANOVA) model.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Integrated Study (Main + Japan Sub-study): Placebo, Integrated Study (Main + Japan Sub-study): Adalimumab
	Comments	The statistical test for the ranked secondary variables was carried out in hierarchical order at the significance level of 5%.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.174
	Comments
	Method	ANOVA
	Comments	From ANOVA with treatment, race (Japanese versus non-Japanese) and OCT machine as factors adjusted for clustered observations.
Method of Estimation	Estimation Parameter	Mean Difference
	Estimated Value	-3.9
	Confidence Interval	(2-Sided) 95%; -9.7 to 1.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	The mean difference between treatment groups with its 95% confidence interval is based on individual data from all eyes adjusted for correlated measurements within a subject in an analysis of variance (ANOVA) model.

7. Secondary Outcome

Title	Change in Visual Functioning Questionnaire 25 (VFQ-25) Total Score From Baseline to the Final/Early Termination Visit
Description	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.
Time Frame	Baseline and Final/Early Termination Visit (up 80 weeks)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Main Study: Placebo	Main Study: Adalimumab	Integrated Study (Main + Japan Sub-study): Placebo	Integrated Study (Main + Japan Sub-study): Adalimumab
Arm/Group Description	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.	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.	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.	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.
Measure Participants	109	115	125	131
Mean (Standard Deviation) [units on a scale]	1.24 (10.698)	3.36 (11.73)	1.00 (10.225)	2.79 (12.018)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Main Study: Placebo, Main Study: Adalimumab
	Comments	The statistical test for the ranked secondary variables was carried out in hierarchical order at the significance level of 5%.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.160
	Comments
	Method	ANOVA
	Comments	From ANOVA of change from baseline to final/early termination visit with treatment as a factor.
Method of Estimation	Estimation Parameter	Mean Difference
	Estimated Value	2.12
	Confidence Interval	(2-Sided) 95%; -0.84 to 5.08
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Integrated Study (Main + Japan Sub-study): Placebo, Integrated Study (Main + Japan Sub-study): Adalimumab
	Comments	The statistical test for the ranked secondary variables was carried out in hierarchical order at the significance level of 5%.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.205
	Comments
	Method	ANOVA
	Comments	From ANOVA of change from baseline to final/early termination visit with treatment and race (Japanese versus non-Japanese) as factors.
Method of Estimation	Estimation Parameter	Mean Difference
	Estimated Value	1.77
	Confidence Interval	(2-Sided) 95%; -0.97 to 4.52
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Change in VFQ-25 Subscore Distance Vision From Baseline to the Final/Early Termination Visit
Description	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.
Time Frame	Baseline and Final/Early Termination Visit (up 80 weeks)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Main Study: Placebo	Main Study: Adalimumab	Integrated Study (Main + Japan Sub-study): Placebo	Integrated Study (Main + Japan Sub-study): Adalimumab
Arm/Group Description	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.	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.	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.	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.
Measure Participants	109	115	125	131
Mean (Standard Deviation) [units on a scale]	0.76 (16.248)	2.64 (17.165)	0.60 (15.978)	2.96 (17.121)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Main Study: Placebo, Main Study: Adalimumab
	Comments	The statistical test for the ranked secondary variables was carried out in hierarchical order at the significance level of 5%.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.401
	Comments
	Method	ANOVA
	Comments	From ANOVA of change from baseline to final/early termination visit with treatment as a factor.
Method of Estimation	Estimation Parameter	Mean Difference
	Estimated Value	1.88
	Confidence Interval	(2-Sided) 95%; -2.53 to 6.29
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Integrated Study (Main + Japan Sub-study): Placebo, Integrated Study (Main + Japan Sub-study): Adalimumab
	Comments	The statistical test for the ranked secondary variables was carried out in hierarchical order at the significance level of 5%.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.256
	Comments
	Method	ANOVA
	Comments	From ANOVA of change from baseline to final/early termination visit with treatment and race (Japanese versus non-Japanese) as factors.
Method of Estimation	Estimation Parameter	Mean Difference
	Estimated Value	2.36
	Confidence Interval	(2-Sided) 95%; -1.73 to 6.45
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Change in VFQ-25 Subscore Near Vision From Baseline to the Final/Early Termination Visit
Description	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.
Time Frame	Baseline and Final/Early Termination Visit (up 80 weeks)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Main Study: Placebo	Main Study: Adalimumab	Integrated Study (Main + Japan Sub-study): Placebo	Integrated Study (Main + Japan Sub-study): Adalimumab
Arm/Group Description	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.	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.	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.	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.
Measure Participants	109	115	125	131
Mean (Standard Deviation) [units on a scale]	3.98 (17.397)	3.88 (18.302)	3.73 (17.17)	2.89 (50.503)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Main Study: Placebo, Main Study: Adalimumab
	Comments	The statistical test for the ranked secondary variables was carried out in hierarchical order at the significance level of 5%.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.967
	Comments
	Method	ANOVA
	Comments	From ANOVA of change from baseline to final/early termination visit with treatment as a factor.
Method of Estimation	Estimation Parameter	Mena Difference
	Estimated Value	-0.10
	Confidence Interval	(2-Sided) 95%; -4.81 to 4.61
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Integrated Study (Main + Japan Sub-study): Placebo, Integrated Study (Main + Japan Sub-study): Adalimumab
	Comments	The statistical test for the ranked secondary variables was carried out in hierarchical order at the significance level of 5%.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.714
	Comments
	Method	ANOVA
	Comments	From ANOVA of change from baseline to final/early termination visit with treatment and race (Japanese versus non-Japanese) as factors.
Method of Estimation	Estimation Parameter	Mean Difference
	Estimated Value	-0.87
	Confidence Interval	(2-Sided) 95%; -5.53 to 3.79
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Change in VFQ-25 Subscore Ocular Pain From Baseline to the Final/Early Termination Visit
Description	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.
Time Frame	Baseline and Final/Early Termination Visit (up 80 weeks)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Main Study: Placebo	Main Study: Adalimumab	Integrated Study (Main + Japan Sub-study): Placebo	Integrated Study (Main + Japan Sub-study): Adalimumab
Arm/Group Description	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.	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.	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.	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.
Measure Participants	109	115	125	131
Mean (Standard Deviation) [units on a scale]	2.87 (17.233)	3.42 (21.32)	2.60 (17.339)	2.15 (21.689)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Main Study: Placebo, Main Study: Adalimumab
	Comments	The statistical test for the ranked secondary variables was carried out in hierarchical order at the significance level of 5%.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.830
	Comments
	Method	ANOVA
	Comments	From ANOVA of change from baseline to final/early termination visit with treatment as a factor.
Method of Estimation	Estimation Parameter	Mean Difference
	Estimated Value	0.56
	Confidence Interval	(2-Sided) 95%; -4.56 to 5.68
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Integrated Study (Main + Japan Sub-study): Placebo, Integrated Study (Main + Japan Sub-study): Adalimumab
	Comments	The statistical test for the ranked secondary variables was carried out in hierarchical order at the significance level of 5%.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.842
	Comments
	Method	ANOVA
	Comments	From ANOVA of change from baseline to final/early termination visit with treatment and race (Japanese vs. non-Japanese) as factors.
Method of Estimation	Estimation Parameter	Mean Difference
	Estimated Value	-0.49
	Confidence Interval	(2-Sided) 95%; -5.32 to 4.34
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	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.
Arm/Group Title	Placebo		Adalimumab
Arm/Group Description	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.		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.
All Cause Mortality
	Placebo		Adalimumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Adalimumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/130 (7.7%)		8/131 (6.1%)
Blood and lymphatic system disorders
NEUTROPENIA	0/130 (0%)		1/131 (0.8%)
Cardiac disorders
CARDIAC TAMPONADE	0/130 (0%)		1/131 (0.8%)
Eye disorders
BLINDNESS TRANSIENT	0/130 (0%)		1/131 (0.8%)
CHOROIDAL NEOVASCULARISATION	1/130 (0.8%)		0/131 (0%)
RETINAL DETACHMENT	1/130 (0.8%)		0/131 (0%)
SUBRETINAL FLUID	1/130 (0.8%)		0/131 (0%)
Gastrointestinal disorders
DYSPHAGIA	0/130 (0%)		1/131 (0.8%)
Infections and infestations
BRONCHITIS	0/130 (0%)		1/131 (0.8%)
MENINGITIS ASEPTIC	1/130 (0.8%)		0/131 (0%)
PNEUMONIA	0/130 (0%)		1/131 (0.8%)
PNEUMONIA LEGIONELLA	0/130 (0%)		1/131 (0.8%)
TONSILLITIS	1/130 (0.8%)		0/131 (0%)
Injury, poisoning and procedural complications
FIBULA FRACTURE	0/130 (0%)		1/131 (0.8%)
HUMERUS FRACTURE	1/130 (0.8%)		0/131 (0%)
Musculoskeletal and connective tissue disorders
ARTHRITIS	1/130 (0.8%)		0/131 (0%)
OSTEONECROSIS	1/130 (0.8%)		0/131 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
LUNG ADENOCARCINOMA STAGE IV	0/130 (0%)		1/131 (0.8%)
Nervous system disorders
DYSARTHRIA	0/130 (0%)		1/131 (0.8%)
STATUS MIGRAINOSUS	0/130 (0%)		1/131 (0.8%)
Respiratory, thoracic and mediastinal disorders
EPISTAXIS	0/130 (0%)		1/131 (0.8%)
PLEURISY	0/130 (0%)		1/131 (0.8%)
Vascular disorders
AORTIC DISSECTION	0/130 (0%)		1/131 (0.8%)
DEEP VEIN THROMBOSIS	2/130 (1.5%)		0/131 (0%)
HYPERTENSIVE CRISIS	1/130 (0.8%)		0/131 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Adalimumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	78/130 (60%)		88/131 (67.2%)
Eye disorders
CYSTOID MACULAR OEDEMA	7/130 (5.4%)		7/131 (5.3%)
DRY EYE	8/130 (6.2%)		5/131 (3.8%)
EYE PAIN	6/130 (4.6%)		9/131 (6.9%)
UVEITIS	9/130 (6.9%)		6/131 (4.6%)
VISUAL ACUITY REDUCED	10/130 (7.7%)		6/131 (4.6%)
Gastrointestinal disorders
DIARRHOEA	9/130 (6.9%)		4/131 (3.1%)
NAUSEA	9/130 (6.9%)		4/131 (3.1%)
General disorders
FATIGUE	9/130 (6.9%)		14/131 (10.7%)
INJECTION SITE PAIN	9/130 (6.9%)		8/131 (6.1%)
PYREXIA	8/130 (6.2%)		6/131 (4.6%)
Infections and infestations
INFLUENZA	7/130 (5.4%)		3/131 (2.3%)
NASOPHARYNGITIS	20/130 (15.4%)		23/131 (17.6%)
SINUSITIS	4/130 (3.1%)		8/131 (6.1%)
UPPER RESPIRATORY TRACT INFECTION	3/130 (2.3%)		10/131 (7.6%)
URINARY TRACT INFECTION	11/130 (8.5%)		13/131 (9.9%)
Investigations
ALANINE AMINOTRANSFERASE INCREASED	1/130 (0.8%)		9/131 (6.9%)
ASPARTATE AMINOTRANSFERASE INCREASED	1/130 (0.8%)		8/131 (6.1%)
Musculoskeletal and connective tissue disorders
ARTHRALGIA	12/130 (9.2%)		28/131 (21.4%)
BACK PAIN	7/130 (5.4%)		10/131 (7.6%)
PAIN IN EXTREMITY	3/130 (2.3%)		10/131 (7.6%)
Nervous system disorders
HEADACHE	17/130 (13.1%)		17/131 (13%)
Psychiatric disorders
INSOMNIA	3/130 (2.3%)		9/131 (6.9%)
Respiratory, thoracic and mediastinal disorders
COUGH	6/130 (4.6%)		11/131 (8.4%)
Vascular disorders
HYPERTENSION	5/130 (3.8%)		7/131 (5.3%)

Limitations/Caveats

[Not Specified]

More Information

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

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