Topical Interleukin 1 Receptor Antagonist for Treatment of Dry Eye Disease

Abstract

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.