An international research collaboration between US and EU clinical investigators, led by Duke University, Durham, North Carolina, has shown that adalimumab, an anti-TNF-α antagonist, marketed by AbbVie Inc. (NYSE: ABBV), may have application in the treatment of active noninfectious intermediate uveitis, posterior uveitis, or panuveitis. The drug, a recombinant DNA-derived human immunoglobulin G1 (IgG1) monoclonal antibody specific for human tumor necrosis factor alpha (TNF-α), is currently approved by the FDA for the treatment of rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, moderate to severe chronic psoriasis and juvenile idiopathic arthritis. Results of a randomised phase 3 multicentre trial in uveitis patients has shown that patients treated with adalimumab were less likely to suffer treatment failure than control participants.
According to the clinical research group, uveitis has an “estimated incidence of 17 to 52 cases per 100,000 person-years and is estimated to cause 10 to 15% of cases of blindness in Western countries”. Previous research has indicated that pro-inflammatory cytokine tumor necrosis factor α (TNF-α) plays a key role in the inflammation process which characterizes uveitis and that TNF-α levels are up-regulated in the serum and aqueous humor of uveitis patients. In addition, previous uncontrolled case series, retrospective chart reviews and small open-label studies had hinted there may be a beneficial effect in treating patients with chronic or refractory uveitis. To establish more robust evidence for adalimumab, 217 patients were included in an intention-to-treat analyses performed between August 10, 2010, and August 29, 2014.
Conducted as a multinational phase 3 trial the study enrolled uveitis patients who were randomly assigned in a 1:1 ratio to receive adalimumab (loading dose of 80 mg followed by a dose of 40 mg every 2 weeks) or a matched placebo. Analysis of the results showed that the median time to treatment failure was 24 weeks for the adalimumab group and 13 weeks for the placebo group. According to the researchers, “among the 217 patients in the intention-to-treat population, those receiving adalimumab were less likely than those in the placebo group to have treatment failure (hazard ratio, 0.50; 95% confidence interval, 0.36 to 0.70; P<0.001).” In addition, the research demonstrated that secondary outcomes including change in anterior chamber cell grade, change in vitreous haze grade, and change in BCVA, were all significantly better in the treatment group. Finally, adverse events, including serious adverse events, were more frequent among adalimumab patients compared to controls (1052.4 vs. 971.7 adverse events and 28.8 vs. 13.6 serious adverse events per 100 person-years). Commenting on the results one of the study authors, Dr. Talin Barisani-Asenbauer MD, PhD stated, “we were able to prospectively demonstrate for the very first time that non-infectious uveitis can also be successfully treated with a cortisol-free medication. That will significantly improve the management of uveitis patients who have only partially responded to corticosteroids, need a corticosteroid sparing therapy or who are unsuitable for treatment with corticosteroids.”