Uveitis Patient Selection Key for Adalimumab Treatment

Noninfectious uveitis is a vision threatening rheumatologic disease that can be devastating to patients who suffer from it.  When patients are faced with possible blindness it is very important to pursue any therapy that offers symptom relief as well as extended remission of the inflammation that leads to vision loss.

The unpleasant long-term side effects of steroid therapy for noninfectious uveitis coupled with treatment failure rates make the need for alternative therapies of great importance. Numerous preliminary studies suggest that the anti-tumor necrosis factor-alpha monoclonal antibody (anti-TNF-α) adalimumab is effective in treating chronic or refractory uveitis and may reduce steroid use.

A study published in the Sept. 8 issue of the New England Journal of Medicine, finds that “adalimumab was found to be associated with a lower risk of uveitic flare or visual impairment and with more adverse events and serious adverse events than was placebo.” This was an 18-country, four-year phase three trial of adults with active noninfectious intermediate uveitis, posterior uveitis, or panuveitis. The objective of this study was to assess the efficacy of adalimumab to control uveitis. Patients were randomly assigned to placebo or a treatment group (217 patients).

What makes this study important and novel is that it represents the first prospective randomized investigation examining adalimumab for the treatment of noninfectious uveitis.

The benefit in length of time before treatment failure was modest, on the order of 28 percent fewer than placebo. This information should be taken in the context that after 35 weeks of treatment in both groups, failure rates plateau with placebo patients seeing approximately an 80 percent failure rate and adalimumab patients a long term failure rate of 60 percent. Common manifestations of treatment failure were serious and included haziness in the vitreous humor, new inflammatory lesions forming and worsening of prior best corrected vision. It is important to recognize that the majority of patients treated with either steroids or adalimumab will experience treatment failure at some point.

Adalimumab:  A longer period of relief

While treatment with adalimumab resulted in a longer period of relief before treatment failure, it was also associated with significantly more serious adverse events than placebo. The increased number of adverse events in the adalimumab group lead to 13 of the 111 participants withdrawal from the trial. The events that lead to withdrawal included blurred vision, reduced vision, fatigue, malaise and in some cases suicidal ideation. More common adverse events included:  Injection site reactions, allergic reactions, and infections. Ultimately adalimumab was able to control multiple aspects of uveitic inflammation for longer than glucocorticoid steroid treatment. Haze within the vitreous humor was the most common cause of treatment failure and was one third less likely in the adalimumab group.

Conclusion

It is clear that treatment with adalimumab has advantages over no treatment or conventional treatment with steroid therapy. Adalimumab is a promising alternative to steroid treatment and or an option following steroid therapy failure. Proper patient selection is important and should take into account the patient’s overall health and their risk of developing opportunistic infections. Long-term treatment success may be possible in up to 20 percent of patients, which offers a hopeful outlook for many who suffer from this devastating disease.

Disclosures:

The study featured in this review was funded by AbbVie; VISUAL I, ClinicalTrials.gov number NCT01138657.

References:

Jaffe GJ, Dick AD, Brezin AP, et al. “Adalimumab in patients with active noninfectious uveitis.” New England Journal of Medicine. 2016;375:932-43.
DOI: 10.1056/NEJMoa1509852 www.nejm.org/doi/full/10.1056/NEJMoa1509852