Contemporary approaches to uveitis treatment should include biologic therapy, according to two recent studies. One noted an association between tumor necrosis factor-α inhibitors (TNFi) and long-term drug-induced remission of ocular inflammation, visual stability and corticosteroid function.1 The other provides a review of the biologic agents clinicians are currently using to successfully treat non-infectious uveitis, as well as therapeutics currently under investigation.2

TNFi Therapy

Researchers in the United Kingdom carried out a prospective cohort study of infliximab and adalimumab to treat non-infectious ocular inflammatory disease.1 From 2006 to 2014, they followed 43 adults with non-infectious uveitis or scleritis, 34 of whom were taking infliximab and nine were on adalimumab.1

The median time on infliximab and adalimumab was 3.2 years and 2.4 years, respectively. Treatment induced sustained remission in 39 patients (91%) after a median of 1.2 years on a TNFi. Researchers discovered that 22 (51%) experienced one relapse and five (12%) had two relapses. While 54% had at least one adverse event, serious adverse events necessitating hospitalization or cessation of medication occurred in only 9% of patients. In eight patients who had active inflammation, cystoid macular edema and vitritis were the main features. Ten patients switched to another TNFi or another class of biologic therapy after 1.7 years of the initial therapy.1

This prospective report suggests long-term TNFi is associated with no attrition of quality of life, despite the need for ongoing treatment and mild side effects. Serious adverse events were infrequent but were an appreciable risk. Despite the inhibitors’ successes, the researchers call for wider treatment options and further assessment of which etiologies respond best to specific therapies.1

Research Roundup

Data supporting the efficacy of biologics for uveitis have led to adalimumab’s FDA approval for most forms of non-infectious uveitis and clinical trials for other biologic pharmaceuticals. Given the relative rarity and heterogeneity of non-infectious uveitis, limited large multicenter prospective clinical trials exist examining the efficacy of these biologics, specifically for the treatment of non-infectious uveitis. Therefore, much of the published research on biologics for uveitis includes small prospective trials, retrospective series and observational studies of uveitis control in patients on biologics for other approved systemic indications. A recent review assessed the findings from these sources to highlight the current and investigational biologic agents.2

The review found that adalimumab and infliximab are considered second-line therapeutics for most forms of non-infectious uveitis but may be considered first-line agents in uveitis associated with Behçet’s disease and juvenile idiopathic arthritis. It also strongly recommends adalimumab and infliximab before etanercept for the management of ocular inflammatory disease.2

 Researchers have documented the efficacy of rituximab, a B-cell inhibitor, in the treatment of scleritis, ocular cicatricial pemphigoid, orbital inflammatory disease and many forms of non-infectious uveitis. Tocilizumab and interferon therapy also appear to be efficacious in the management of refractory uveitic macular edema. According to the review, interleukin-23 inhibitors mechanistically seem effective in the treatment of non-infectious uveitis, but data is lacking. Meanwhile, Phase II clinical trials are investigating the efficacy of Janus kinase inhibitors.2

Although certain biologics can be first-line agents for the treatment of some forms of uveitis, the review notes that biologics are considered second-line or third-line agents for the majority of these patients. The most common scenario in which a biologic agent is used in non-infectious uveitis is for patients for whom conventional immunomodulatory therapy is poorly tolerated or incompletely effective.2

1. Sharma SM, Damato E, Hinchcliffe AEet al. Long-term efficacy and tolerability of TNFα inhibitors in the treatment of non-infectious ocular inflammation: an eight-year prospective surveillance study. Br J Ophthalmol. March 12, 2019. [Epub ahead of print].

2. Biologics for the treatment of noninfectious uveitis: current concepts and emerging therapeutics. Thomas AS. Curr Opin Ophthalmol. March 5, 2019. [Epub ahead of print].