Gevokizumab in the treatment of autoimmune, non-necrotizing, anterior scleritis: Results of a phase I/II clinical trial

• Published in: American journal of ophthalmology Vol. 172; pp. 104 - 110
• Main Authors: Knickelbein, Jared E, Tucker, William R, Bhatt, Nirali, Armbrust, Karen, Valent, David, Obiyor, Dominic, Nussenblatt, Robert B, Sen, H. Nida
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2016; Elsevier Limited
• Subjects: Adult; Aged; Aged, 80 and over; Anterior Eye Segment - diagnostic imaging; Antibodies, Monoclonal, Humanized - administration & dosage; Autoimmune Diseases - diagnosis; Autoimmune Diseases - drug therapy; Autoimmune Diseases - immunology; Autoimmunity; Cytokines; Diabetic retinopathy; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug dosages; Female; Follow-Up Studies; Humans; Injections, Subcutaneous; Irritable bowel syndrome; Male; Middle Aged; Nonsteroidal anti-inflammatory drugs; Ophthalmology; Pilot Projects; Prospective Studies; Rheumatoid arthritis; Scleritis - diagnosis; Scleritis - drug therapy; Scleritis - immunology; Treatment Outcome; Visual Acuity; United States > US; California
• ISSN: 0002-9394; 1879-1891
• DOI: 10.1016/j.ajo.2016.09.017

Abstract Purpose To evaluate the safety and potential efficacy of gevokizumab, an anti-interleukin 1β (IL-1β) monoclonal antibody, in the treatment of active, non-infectious, non-necrotizing, anterior scleritis. Design Phase 1/2, open label, non-randomized, prospective, single-arm, pilot trial Methods Eight patients with active, non-infectious, non-necrotizing, anterior scleritis with a scleral inflammatory grade of +1 to +3 in at least one eye were enrolled. In one patient, both eyes were enrolled, for a total of nine eyes (four eyes with +1, one eye with +2, and four eyes with +3). Patients received one subcutaneous injection of 60 mg gevokizumab at baseline and then every four weeks for 12 weeks. Complete physical and ocular examinations were performed at each visit. The primary outcome was at least a 2-step reduction or reduction to grade 0 in scleral inflammation on a 0 to +4 scale according to a standardized photographic scleritis grading system by 16 weeks in the study eye compared to baseline. Secondary outcomes included changes in visual acuity, intraocular pressure, and trends in scleral grading. Participants who met the primary outcome were eligible to continue in the study for up to 52 weeks and received additional gevokizumab injections every four weeks until week 36 followed by two safety visits at weeks 40 and 52. Results Seven eyes from seven patients met the primary outcome within a median time of two weeks following the first gevokizumab injection. No definitive changes in visual acuity or IOP were identified. There were no serious adverse events related to the study drug. A total of 43 adverse effects were reported with 93% described as mild, 95% as non-ocular, and only 14% deemed possibly caused by the investigational treatment. Conclusions The results of this small study suggest that blockage of IL-1β using gevokizumab may be beneficial in treating active, non-infectious, anterior scleritis and that gevokizumab is well-tolerated. Larger randomized trials are warranted to assess the true efficacy of gevokizumab in the treatment of non-necrotizing anterior scleritis.