Adalimumab in Patients With Active and Inactive Noninfectious Uveitis
The effectiveness of adalimumab (Humira, AbbVie) for noninfectious intermediate, posterior, and panuveitis—that is, for various forms of noninfectious uveitis (NIU)—was studied in two large, multinational, phase 3 clinical trials. The results of these studies have been released in paired publications this month in two major medical journals. The VISUAL 1 study, the results of which were published this month in the New England Journal of Medicine, enrolled 217 patients with active NIU.1 The VISUAL 2 study, published online this month in The Lancet, enrolled 226 corticosteroid-dependent patients with inactive NIU.2
In both studies, patients were randomized to receive either adalimumab or placebo subcutaneous injections. The regimen consisted of a loading dose of 80 mg adalimumab (or placebo), a 40-mg dose 1 week later, and then 40 mg every 2 weeks. VISUAL 1 required patients to undergo a 2-week prednisone burst to 60 mg with a forced tapering off of all corticosteroids by study week 15; VISUAL 2 did not require a steroid burst, but required a corticosteroid taper over 19 weeks. Both studies used a primary endpoint of time to treatment failure (TTF), defined by a composite endpoint that included 2-step worsening of anterior chamber cell or vitreous haze, the occurrence of new inflammatory retinal or retinovascular lesions, or a 15 ETDRS letter worsening in vision. The primary outcome assessment for both studies was at 6 months, but patients were followed for a total of 18 months.
For the VISUAL 1 study, the median TTF was 24 weeks in the adalimumab group and 13 weeks in the placebo group. There was a 28% absolute reduction in risk of treatment failure (TF) in the adalimumab group relative to placebo at the 6-month time point. Hazard ratio for TF during 18 months of follow-up was 0.50, suggesting that risk of TF in the adalimumab group was reduced 50% relative to the placebo group over the duration of the study.
For the VISUAL 2 study, the median TTF was not estimable in the adalimumab group (due to total TF rate <50%), and was 8.3 months in the placebo group. A similar analysis using 40th percentile TTF found TTF of 10.2 months and 4.8 months for adalimumab and placebo, respectively. Hazard ratio for TF during 18 months of follow-up was 0.57, suggesting a 43% reduction of TF risk in the adalimumab group relative to placebo over the duration of the study.
For both studies, the separation between the adalimumab and placebo groups was early (6 weeks and 2 weeks in VISUAL 1 and VISUAL 2, respectively) and was sustained over 18 months.
Adverse events reported in both studies were consistent with adalimumab studies for other indications, including headache, localized infection, and injection-site reaction. More serious but uncommon reported events included malignancy, active tuberculosis, lupus or lupus-like reaction, and demyelinating disorder.
These studies suggest a beneficial effect of adalimumab in the treatment of both active and corticosteroid-dependent inactive NIU. Physicians who wish to consider the use of adalimumab for the treatment of NIU should be familiar with these studies, as well as with the safety considerations described, and should appropriately screen patients for tuberculosis, other latent infections, and demyelinating disease prior to starting adalimumab or any biologic medication.
1. Jaffe GJ, Dick AD, Brézin AP. Adalimumab in patients with active noninfectious uveitis. N Engl J Med. 2016;375(10):932-943.
2. Nguyen QD, Merrill PT, Jaffe GJ. 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 [published online ahead of print August 16, 2016]. Lancet.
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