TNF inhibition for ophthalmic indications: current status and outlook

Tumor necrosis factors (TNF) are a group of cytokines that play a role in systemic inflammation, stimulating the acute phase reaction. They are involved in systemic rheumatologic conditions such as rheumatoid arthritis and juvenile idiopathic arthritis, as well as ocular inflammatory conditions in the uveitis spectrum. Several drugs were developed to inhibit the action of TNF, thereby reducing inflammation. The three most commonly used TNF inhibitors in the US are etanercept, infliximab, and adalimumab. Newer drugs include certolizumab and golimumab. In this review, we discuss the differences in the mechanism of action, route of administration, indication, and efficacy of TNF inhibitors used in the treatment of ocular inflammation.A review of the literature in the PubMed, MEDLINE, and Cochrane databases was conducted to identify clinical trials, comparative studies, case series, and case reports describing the use of tumor necrosis factor inhibitors in uveitis therapy. The search was limited to primary reports published in English with human subjects from 1990 to the present, yielding 5,238 manuscripts. In addition, referenced articles from the initial searches were hand searched to identify additional relevant reports. After title and abstract selection, duplicate elimination, and manual search, 69 papers were selected for analysis. Exclusion criteria included review articles and case reports on the efficacy of etanercept, infliximab, and adalimumab. Manuscripts with fewer than 20 study subjects were excluded if other larger studies existed on the use of the same drug for a particular indication. Studies with6 months of patient follow-up were also excluded, except in the case where no other data were available. Articles meeting these criteria were then reviewed by the three authors for inclusion in this review.Tumor necrosis factor inhibitors have been shown to decrease inflammation associated with a number of rheumatologic conditions. Three of the five commercially available TNF inhibitors-etanercept, infliximab, and adalimumab-have been studied for their efficacy in treatment of ocular inflammation. Etanercept appears to be inadequate in controlling ocular inflammation and is not recommended for the treatment of uveitis. Infliximab and adalimumab, however, have shown encouraging results in multiple trials. Serious potential side effects such as infection, including reactivation of latent tuberculosis, malignancy, and demyelinating disease, may limit the use of TNF inhibitors in uveitis. Proper screening of patients prior to initiating these therapies may decrease these risks.Early success with infliximab and adalimumab has paved the way for new TNF inhibitors and other corticosteroid-sparing drugs to emerge in the treatment of ocular inflammation. Future studies are on the horizon to determine the long-term safety and efficacy of newer TNF inhibitors such as certolizumab and golimumab.