Topical interleukin 1 receptor antagonist for treatment of dry eye disease: A randomized clinical trial

Importance: The immunopathogenic mechanisms of dry eye disease (DED), one of the most common ophthalmic conditions, is incompletely understood. Data from this prospective, double-masked, randomized trial demonstrate that targeting interleukin 1 (IL-1) by topical application of an IL-1 antagonist is efficacious in significantly reducing DED-related patient symptoms and corneal epitheliopathy. Objective: To evaluate the safety and efficacy of treatment with the topical IL-1 receptor antagonist anakinra (Kineret; Amgen Inc) in patients having DED associated with meibomian gland dysfunction. Design and Setting: Prospective phase 1/2, randomized, double-masked, vehicle-controlled clinical trial. Participants: Seventy-five patients with refractory DED. Interventions: Participants were randomized to receive treatment with topical anakinra, 2.5% (n=30), anakinra, 5% (n=15), or vehicle (1% carboxymethylcellulose) (n=30) 3 times daily for 12 weeks. Main Outcomes and Measures: Primary outcomes were corneal fluorescein staining (CFS), complete bilateral CFS clearance, dry eye-related symptoms as measured by the Ocular Surface Disease Index, tear film breakup time, and meibomian gland secretion quality. Results: Topical anakinra was well tolerated compared with vehicle, with no reports of serious adverse reactions attributable to the therapy. After 12 weeks of therapy, participants treated with anakinra, 2.5%, achieved a 46% reduction in their mean CFS score (P =.12 compared with vehicle and P <.001 compared with baseline); participants treated with anakinra, 5%, achieved a 17% reduction in their mean CFS score (P =.88 compared with vehicle and P =.33 compared with baseline); and patients treated with vehicle achieved a 19% reduction in their mean CFS score (P =.11). Complete bilateral CFS clearance was noted in 8 of 28 patients (29%) treated with anakinra, 2.5%, vs in 2of 29 patients (7%) treated with vehicle (P =.03). By week 12, treatment with anakinra, 2.5%, and treatment with anakinra, 5%, led to significant reductions in symptoms of 30% and 35%, respectively (P =.02 and P =.01, respectively, compared with vehicle); treatment with vehicle led to a 5% reduction in symptoms. Conclusions and Relevance: Treatment with topical anakinra, 2.5%, for 12 weeks was safe and significantly reduced symptoms and corneal epitheliopathy in patients with DED. These data suggest that the use of an IL-1 antagonist may have a role as a novel therapeutic option for patients with DED. Trial Registration: clinicaltrials.gov Identifier: NCT00681109. ©2013 American Medical Association. All rights reserved.