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

• ClinicalTrials.gov Identifier: NCT01124838
• Recruitment Status: Completed
• First Posted: May 17, 2010
• Results First Posted: June 21, 2016
• Last Update Posted: July 7, 2021
• Sponsor: AbbVie (prior sponsor, Abbott)
• Information provided by (Responsible Party): AbbVie ( AbbVie (prior sponsor, Abbott) )

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Uveitis
• Interventions: Drug: Adalimumab; Drug: Prednisone; Drug: Placebo
• Enrollment: 261

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 Details	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
Reason Not Completed
Miscellaneous	4	2
Adverse Event	7	11
Lack of Efficacy	2	0
Withdrawal by Subject	3	2
Lost to Follow-up	2	0

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 Number of Baseline Participants		130	131	261
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	130 participants	131 participants	261 participants
		43.22 (14.026)	43.18 (12.719)	43.20 (13.360)
Age, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	130 participants	131 participants	261 participants
< 65 years		121	125	246
≥ 65 years		9	6	15
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	130 participants	131 participants	261 participants
	Female	83 63.8%	75 57.3%	158 60.5%
	Male	47 36.2%	56 42.7%	103 39.5%
Race/Ethnicity, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	130 participants	131 participants	261 participants
White		96	96	192
Black		8	6	14
Asian		19	19	38
American Indian/Alaskan Native		1	0	1
Native Hawaiian or Other Pacific Islander		0	0	0
Other		5	9	14
Multi-Race		1	1	2
Type of Uveitis; Measure Type: Number; Unit of measure: Participants	Number Analyzed	130 participants	131 participants	261 participants
Intermediate		30	17	47
Posterior		36	41	77
Panuveitis		63	71	134
Intermediate/Posterior		1	2	3
Diagnosis; Measure Type: Number; Unit of measure: Participants	Number Analyzed	130 participants	131 participants	261 participants
Idiopathic		45	33	78
Birdshot Choroidopathy		16	15	31
Multifocal Choroiditis and Panuveitis		2	5	7
Vogt Koyanagi Harada		30	34	64
Sarcoid		20	22	42
Behcet's		7	10	17
Other		10	12	22
Eye Affected; Measure Type: Number; Unit of measure: Participants	Number Analyzed	130 participants	131 participants	261 participants
Left		3	3	6
Right		5	2	7
Both		122	126	248
History of Infectious Uveitis; Measure Type: Number; Unit of measure: Participants	Number Analyzed	130 participants	131 participants	261 participants
Yes		0	0	0
No		130	131	261
Duration of Uveitis; Mean (Standard Deviation); Unit of measure: Months
	Number Analyzed	130 participants	131 participants	261 participants
		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.
Overall Number of Participants Analyzed	111	115	127	131
Median (Inter-Quartile Range); Unit of Measure: months
	8.3 [1]; (3.0 to NA)	NA [1]; (4.7 to NA)	5.6 [1]; (2.6 to NA)	NA [1]; (3.9 to NA)

[1]

Not estimable due to the low number of events

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	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.004
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.57
	Confidence Interval	(2-Sided) 95%; 0.39 to 0.84
	Estimation Comments	[Not Specified]

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	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.52
	Confidence Interval	(2-Sided) 95%; 0.37 to 0.74
	Estimation Comments	[Not Specified]

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.
Overall Number of Participants Analyzed	110	115	126	131
Mean (Standard Deviation); Unit of Measure: units on a scale
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	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.218
	Comments	[Not Specified]
	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
	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	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.164
	Comments	[Not Specified]
	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
	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.
Overall Number of Participants Analyzed	110	115	126	131
Mean (Standard Deviation); Unit of Measure: units on a scale
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	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.070
	Comments	[Not Specified]
	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
	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	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.016
	Comments	[Not Specified]
	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
	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.
Overall Number of Participants Analyzed	110	115	126	131
Mean (Standard Deviation); Unit of Measure: logMAR
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	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.096
	Comments	[Not Specified]
	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
	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	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.044
	Comments	[Not Specified]
	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
	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.
Overall Number of Participants Analyzed	95	90	106	102
Median (Inter-Quartile Range); Unit of Measure: months
	NA [1]; (NA to NA)	NA [1]; (NA to NA)	NA [1]; (NA to NA)	NA [1]; (NA to NA)

[1]

Could not be estimated due to the low number of events

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	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.491
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.75
	Confidence Interval	(2-Sided) 95%; 0.34 to 1.69
	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	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.185
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.60
	Confidence Interval	(2-Sided) 95%; 0.28 to 1.28
	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.
Overall Number of Participants Analyzed	108	114	124	130
Mean (Standard Deviation); Unit of Measure: percent change
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	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.451
	Comments	[Not Specified]
	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
	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	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.174
	Comments	[Not Specified]
	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
	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.
Overall Number of Participants Analyzed	109	115	125	131
Mean (Standard Deviation); Unit of Measure: 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	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.160
	Comments	[Not Specified]
	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
	Estimation Comments	[Not Specified]

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	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.205
	Comments	[Not Specified]
	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
	Estimation Comments	[Not Specified]

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.
Overall Number of Participants Analyzed	109	115	125	131
Mean (Standard Deviation); Unit of Measure: 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	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.401
	Comments	[Not Specified]
	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
	Estimation Comments	[Not Specified]

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	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.256
	Comments	[Not Specified]
	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
	Estimation Comments	[Not Specified]

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.
Overall Number of Participants Analyzed	109	115	125	131
Mean (Standard Deviation); Unit of Measure: 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	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.967
	Comments	[Not Specified]
	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
	Estimation Comments	[Not Specified]

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	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.714
	Comments	[Not Specified]
	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
	Estimation Comments	[Not Specified]

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.
Overall Number of Participants Analyzed	109	115	125	131
Mean (Standard Deviation); Unit of Measure: 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	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.830
	Comments	[Not Specified]
	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
	Estimation Comments	[Not Specified]

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	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.842
	Comments	[Not Specified]
	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
	Estimation Comments	[Not Specified]

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.
Adverse Event Reporting Description	[Not Specified]
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 (%)	Affected / at Risk (%)
Total	--/--	--/--
Serious Adverse Events
	Placebo	Adalimumab
	Affected / at Risk (%)	Affected / at Risk (%)
Total	10/130 (7.69%)	8/131 (6.11%)
Blood and lymphatic system disorders
NEUTROPENIA † 1	0/130 (0.00%)	1/131 (0.76%)
Cardiac disorders
CARDIAC TAMPONADE † 1	0/130 (0.00%)	1/131 (0.76%)
Eye disorders
BLINDNESS TRANSIENT † 1	0/130 (0.00%)	1/131 (0.76%)
CHOROIDAL NEOVASCULARISATION † 1	1/130 (0.77%)	0/131 (0.00%)
RETINAL DETACHMENT † 1	1/130 (0.77%)	0/131 (0.00%)
SUBRETINAL FLUID † 1	1/130 (0.77%)	0/131 (0.00%)
Gastrointestinal disorders
DYSPHAGIA † 1	0/130 (0.00%)	1/131 (0.76%)
Infections and infestations
BRONCHITIS † 1	0/130 (0.00%)	1/131 (0.76%)
MENINGITIS ASEPTIC † 1	1/130 (0.77%)	0/131 (0.00%)
PNEUMONIA † 1	0/130 (0.00%)	1/131 (0.76%)
PNEUMONIA LEGIONELLA † 1	0/130 (0.00%)	1/131 (0.76%)
TONSILLITIS † 1	1/130 (0.77%)	0/131 (0.00%)
Injury, poisoning and procedural complications
FIBULA FRACTURE † 1	0/130 (0.00%)	1/131 (0.76%)
HUMERUS FRACTURE † 1	1/130 (0.77%)	0/131 (0.00%)
Musculoskeletal and connective tissue disorders
ARTHRITIS † 1	1/130 (0.77%)	0/131 (0.00%)
OSTEONECROSIS † 1	1/130 (0.77%)	0/131 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
LUNG ADENOCARCINOMA STAGE IV † 1	0/130 (0.00%)	1/131 (0.76%)
Nervous system disorders
DYSARTHRIA † 1	0/130 (0.00%)	1/131 (0.76%)
STATUS MIGRAINOSUS † 1	0/130 (0.00%)	1/131 (0.76%)
Respiratory, thoracic and mediastinal disorders
EPISTAXIS † 1	0/130 (0.00%)	1/131 (0.76%)
PLEURISY † 1	0/130 (0.00%)	1/131 (0.76%)
Vascular disorders
AORTIC DISSECTION † 1	0/130 (0.00%)	1/131 (0.76%)
DEEP VEIN THROMBOSIS † 1	2/130 (1.54%)	0/131 (0.00%)
HYPERTENSIVE CRISIS † 1	1/130 (0.77%)	0/131 (0.00%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 17.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Placebo	Adalimumab
	Affected / at Risk (%)	Affected / at Risk (%)
Total	78/130 (60.00%)	88/131 (67.18%)
Eye disorders
CYSTOID MACULAR OEDEMA † 1	7/130 (5.38%)	7/131 (5.34%)
DRY EYE † 1	8/130 (6.15%)	5/131 (3.82%)
EYE PAIN † 1	6/130 (4.62%)	9/131 (6.87%)
UVEITIS † 1	9/130 (6.92%)	6/131 (4.58%)
VISUAL ACUITY REDUCED † 1	10/130 (7.69%)	6/131 (4.58%)
Gastrointestinal disorders
DIARRHOEA † 1	9/130 (6.92%)	4/131 (3.05%)
NAUSEA † 1	9/130 (6.92%)	4/131 (3.05%)
General disorders
FATIGUE † 1	9/130 (6.92%)	14/131 (10.69%)
INJECTION SITE PAIN † 1	9/130 (6.92%)	8/131 (6.11%)
PYREXIA † 1	8/130 (6.15%)	6/131 (4.58%)
Infections and infestations
INFLUENZA † 1	7/130 (5.38%)	3/131 (2.29%)
NASOPHARYNGITIS † 1	20/130 (15.38%)	23/131 (17.56%)
SINUSITIS † 1	4/130 (3.08%)	8/131 (6.11%)
UPPER RESPIRATORY TRACT INFECTION † 1	3/130 (2.31%)	10/131 (7.63%)
URINARY TRACT INFECTION † 1	11/130 (8.46%)	13/131 (9.92%)
Investigations
ALANINE AMINOTRANSFERASE INCREASED † 1	1/130 (0.77%)	9/131 (6.87%)
ASPARTATE AMINOTRANSFERASE INCREASED † 1	1/130 (0.77%)	8/131 (6.11%)
Musculoskeletal and connective tissue disorders
ARTHRALGIA † 1	12/130 (9.23%)	28/131 (21.37%)
BACK PAIN † 1	7/130 (5.38%)	10/131 (7.63%)
PAIN IN EXTREMITY † 1	3/130 (2.31%)	10/131 (7.63%)
Nervous system disorders
HEADACHE † 1	17/130 (13.08%)	17/131 (12.98%)
Psychiatric disorders
INSOMNIA † 1	3/130 (2.31%)	9/131 (6.87%)
Respiratory, thoracic and mediastinal disorders
COUGH † 1	6/130 (4.62%)	11/131 (8.40%)
Vascular disorders
HYPERTENSION † 1	5/130 (3.85%)	7/131 (5.34%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 17.0

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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.

Results Point of Contact

• Name/Title: Global Medical Services
• Organization: AbbVie (prior sponsor, Abbott)
• Phone: 800-633-9110

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, Brezin 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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Sheppard J, Joshi A, Betts KA, Hudgens S, Tari S, Chen N, Skup M, Dick AD. Effect of Adalimumab on Visual Functioning in Patients With Noninfectious Intermediate Uveitis, Posterior Uveitis, and Panuveitis in the VISUAL-1 and VISUAL-2 Trials. JAMA Ophthalmol. 2017 Jun 1;135(6):511-518. doi: 10.1001/jamaophthalmol.2017.0603.

• Responsible Party: AbbVie ( AbbVie (prior sponsor, Abbott) )
• ClinicalTrials.gov Identifier: NCT01124838
• Other Study ID Numbers: M10-880; 2009-016008-22 ( EudraCT Number )
• First Submitted: May 14, 2010
• First Posted: May 17, 2010
• Results First Submitted: May 13, 2016
• Results First Posted: June 21, 2016
• Last Update Posted: July 7, 2021