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Eric S Furfine, Reza Dana, Cameron Wheeler, Abbie Celniker, Michael H Goldstein; Topical Interleukin-1 (IL-1) Receptor Inhibition Reduces Ocular Pain. Invest. Ophthalmol. Vis. Sci. 2014;55(13):3686.
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Ocular pain is a common patient symptom in many ophthalmic diseases. Multiple preclinical studies indicate that IL-1β acts directly on IL-1R1 receptors on the surface of neurons throughout the body to induce hyperalgesia. IL-1 agonists are elevated and involved in the inflammation that occurs on ocular surface tissues in dry eye disease (DED), allergic conjunctivitis, LASIK surgery, photorefractive keratectomy and other ocular surface disorders. As the cornea has the densest neuroplexus in the body, blockade of elevated IL-1β in DED might reduce ocular pain and discomfort associated with DED.
EBI-005 is a novel IL-1R1 inhibitor designed and optimized for topical treatment of ocular surface inflammatory disease. A Phase 1b/2a study randomized 74 subject to topical vehicle control or EBI-005 (5 or 20 mg/mL), treated 3x/day for 6 weeks. Symptoms were assessed using the Ocular Surface Disease Index (OSDI). Of the 12 OSDI questions asked of subjects, one of the questions specifically has subjects rate their “painful or sore eyes” (OSDI-Pain score) on a scale 0 - 4 (none to frequent pain). A separate study, treated subjects with topical recombinant IL-1receptor antagonist (IL-1Ra, same mechanism of action as EBI-005) administered three times daily for 12 weeks and assessed OSDI scores. Retrospective analyses assessed the effect of IL-1 blockade on the OSDI-Pain score by comparing change from baseline for the drug-treated and vehicle control groups over the course of the respective treatment phases.
100% of subjects randomized in both trials responded to the OSDI-Pain question. In the EBI-005 trial, subjects receiving EBI-005 (efficacy evaluable) improved from baseline by 46% (0.9 units) in OSDI-pain at 6 weeks, with some improvement as early as two weeks. OSDI-Pain improved by 61% (0.9 units) in subset of subjects with a baseline total OSDI score under 50. For the IL-1Ra trial, subjects improved from baseline by 37% and 36% in OSDI-Pain at 6 and 12 weeks. Corneal esthesiometry showed EBI-005 did not change sensation from baseline over the 6 week treatment.
Two separate studies of subjects with DED treated topically with two different IL-1R1 inhibitors (EBI-005 or IL-1Ra) resulted in substantial improvement in OSDI-Pain score compared to vehicle treatment. These results suggest that blockade of IL-1 agonist signaling in the eye may have direct effects on ocular pain associated with DED.
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