Pharmacotherapy for non-infectious uveitis: spotlight on phase III clinical trials of locally injected or implanted therapeutics and systemic immunomodulatory drugs

Background: Non-infectious uveitis is an uncommon eye condition, but an important cause of substantial vision impairment and blindness around the world. An individualized treatment approach may include corticosteroids, conventional immunomodulatory medications, and biologic immunomodulatory agents, delivered locally to the eye or by systemic routes. 

Body: In this narrative review, we describe pivotal phase III clinical trials that have provided the information guiding clinical practice in non-infectious uveitis today, focusing on studies of injected or surgically positioned local therapeutics, systemic immunomodulatory drugs, and the combination of both. We report on design, outcome measures, and key effectiveness and safety results of these trials. We also describe selected phase III clinical trials that are presently in progress, with results expected within the coming approximately 3 years. Finally, we summarize the state of the field and speculate on fruitful areas of research and development for new phase III clinical trials of drugs to treat non-infectious uveitis. 

Conclusion: The locally delivered therapeutics for non-infectious uveitis that have been studied in phase III clinical trials are largely corticosteroid-based. Trials have shown these locally placed corticosteroids to be effective, with complications that include elevated intraocular pressure and cataract. A minority of systemic immunomodulatory drugs used to treat non-infectious uveitis have been studied in phase III clinical trials. Key information obtained from those trials includes the following: similar effectiveness of methotrexate and mycophenolate mofetil for uveitis involving the posterior eye; usefulness of interferon-beta for intermediate uveitis; and potent anti-inflammatory activity of adalimumab in recalcitrant uveitis. Phase III clinical trials of immunomodulatory drugs with novel targets or routes of delivery can be anticipated in the foreseeable future. Interest in defining treatments for specific subsets of non-infectious uveitis through phase III clinical trials is also likely. For productive cross-referencing of clinical trial results, we recommend the use of core outcome measures.