The authors say that for uveitis â€œthere is a large unmet medical need" for identifying other therapies. Adalimumab is associated with decreased visual impairment and decreased risk of uveitic flare, but more adverse events, according the results from a recent multinational phase 3 trial.
Adalimumab is associated with decreased visual impairment and decreased risk of uveitic flare, but more adverse events, according the results from a recent multinational phase 3 trial. The research is described by Glenn Jaffe, MD, of Duke University in Durham, North Carolina and colleagues, in an article published in the New England Journal of Medicine on September 8, 2016.
The authors say that for uveitis, “glucocorticoids remain the mainstay of therapy despite their well-known ocular and systemic adverse effects,” adding, “there is a large unmet medical need" for identifying other therapies. In seeking novel therapies, researchers have discovered, “the proinflammatory cytokine tumor necrosis factor a (TNF-a) is thought to play a key role in uveitic inflammation, and aqueous humor and serum levels of TNF-a are up-regulated in patients with uveitis.”
Adalimumab is an anti-TNF-a monoclonal antibody which is used to treat other inflammatory conditions. The researchers say, “Uncontrolled case series, retrospective chart reviews, and small open-label studies have suggested that adalimumab is effective in treating patients with chronic or refractory uveitis and in reducing glucocorticoid use.” The present study was undertaken in order “to evaluate the efficacy and safety of an anti-TNF-a drug in patients with active, noninfectious uveitis,” say the authors, adding, “the objective was to assess the efficacy of adalimumab as a glucocorticoid-sparing agent for the control of uveitis.”
There were 217 patients in the intention-to-treat group, with 110 in the adalimumab group and 107 in the placebo group. The researchers report, “The median time to treatment failure was 24 weeks in the adalimumab group and 13 weeks in the placebo group; there was an early and sustained separation of the treatment-failure curves.” Patients receiving adalimumab were less likely to experience treatment failure.
“Adverse events leading to discontinuation of participation in the trial were more common in the adalimumab group and included choroidal neovascularization, blurred vision, reduced visual acuity, fatigue, malaise, and suicidal ideation,” say the researchers. They suggest that the adverse events may be “because of the immunomodulatory action of the drug.” Even though there were more serious adverse events in the adalimumab group, the researchers say “All serious adverse events were unique, and no pattern was identified among the adverse events that led to the discontinuation of adalimumab treatment.”
The authors conclude, “Adalimumab reduced the worsening of several clinically relevant inflammatory measures and significantly lowered the risk of uveitic flare or visual impairment.”