Adalimumab prevented uveitic flare and appeared to control several measures of uveitic inflammation in a manufacturer-sponsored phase III clinical trial.

However, the anti–TNF-alpha monoclonal antibody also was associated with more adverse events and with more serious adverse events, than a matching placebo, including two cancers, reactivation of latent tuberculosis, lupus-like reactions, demyelinating disorder, choroidal neovascularization, and suicidal ideation, Glenn J. Jaffe, MD , of the Duke University Eye Center, Durham, N.C., and his associates reported Sept. 8 in the New England Journal of Medicine.

Based on the results of this VISUAL I trial and another phase III trial, VISUAL II , adalimumab (Humira) was approved by the Food and Drug Administration in July 2016 to treat noninfectious intermediate uveitis, posterior uveitis, and panuveitis in adults.

The results of uncontrolled case series, retrospective chart reviews, and small open-label studies suggested that adalimumab might be effective for chronic or refractory uveitis. Dr. Jaffe and his associates performed a randomized, double-blind study that compared subcutaneous adalimumab with matching placebo, which involved 217 adults with active, noninfectious intermediate or posterior uveitis or panuveitis who were treated at medical centers in 18 countries during a 4-year period. The mean patient age was 43 years, and the mean duration of uveitis was 46 months.

All the participants received a prednisone “burst” (60 mg per day) at entry into the trial, and prednisone was then tapered according to a set schedule until it was fully discontinued by week 15. The primary efficacy endpoint – time to treatment failure at or after week 6 – was 24 weeks for adalimumab, compared with 13 weeks for placebo, the investigators said ( N Engl J Med. 2016;375[10]:932-43 ).

Patients receiving adalimumab were significantly less likely than those receiving placebo to have treatment failure due to progressive vitreous haze (hazard ratio, 0.32), new inflammatory lesions (HR, 0.38), worsening anterior chamber cell grade (HR, 0.51), or worsening of visual acuity (HR, 0.56).

“These observations are consistent with an effect of adalimumab on posterior segment inflammation. Clinically relevant outcomes associated with uveitic inflammation (e.g., grades of anterior chamber cells and vitreous haze, best corrected visual acuity, and central retinal thickness) were significantly better with adalimumab than with placebo,” Dr. Jaffe and his associates added.

The overall rate of adverse events was significantly greater for adalimumab (1,052.4 per 100 person-years) than for placebo (971.1 per 100 person-years), as was the rate of serious adverse events (28.8 vs. 13.6 per 100 person-years, respectively). Serious infections occurred in 8.0 per 100 person-years among patients taking adalimumab and 6.8 per 100 person-years among those taking placebo. Adverse events leading to discontinuation of adalimumab included choroidal neovascularization, blurred vision, reduced visual acuity, fatigue, malaise, and suicidal ideation. Patients in the adalimumab group also reported one case each of tuberculosis, GI cancer, glioblastoma, anaphylaxis, lupus-like reaction, renal failure, and demyelination.

The study was funded by AbbVie, maker of adalimumab, which also conducted the data analysis and wrote the report. Dr. Jaffe reported receiving personal fees from AbbVie, and his associates reported ties to numerous industry sources.