Gevokizumab in the Treatment of Autoimmune Non-necrotizing Anterior Scleritis: Results of a Phase I/II Clinical Trial

Abstract

Purpose: To evaluate the safety and potential efficacy of gevokizumab, an anti-interleukin 1β (IL-1β) monoclonal antibody, in the treatment of active, noninfectious, non-necrotizing anterior scleritis.

Design: Phase 1/2, open label, nonrandomized, prospective, single-arm pilot trial.

Methods: Eight patients with active, noninfectious, non-necrotizing anterior scleritis with a scleral inflammatory grade of +1 to +3 in at least 1 eye were enrolled. In 1 patient both eyes were enrolled, for a total of 9 eyes (4 eyes with +1, 1 eye with +2, and 4 eyes with +3). Patients received 1 subcutaneous injection of 60 mg gevokizumab at baseline and then every 4 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 4 weeks until week 36, followed by 2 safety visits at weeks 40 and 52.

Results: Seven eyes from 7 patients met the primary outcome within a median time of 2 weeks following the first gevokizumab injection. No definitive changes in visual acuity or intraocular pressure 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 nonocular, 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, noninfectious 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.

Conflict of interest statement

Financial Disclosures: No conflicting relationship exists for any author.

Published by Elsevier Inc.

Figures

Figure 1

Scleral photographs of patient 1. Scleral photographs of the inferior left eye were taken after administration of topical phenylephrine 10% at the indicated times in the study. Week 0 was the baseline image before gevokizumab treatment, week 16 was the primary end point after four monthly gevokizumab injections, and week 40 was four weeks following the last gevokizumab injection of the first extension phase.

Figure 2

Graphical representation of clinical scleral grades for all patients. Each scleral quadrant is represented separately. Green blocks represent an inflammatory score of 0, yellow blocks represent trace (0.5+), red blocks represent 2+, and maroon blocks represent 3+. Visit week 52A designates enrollment in the second extension phase, and was different for the three patients (1, 7 & 8) averaging 6.2 months after their week 52 visit.

Figure 3

Scleral photographs of patient 8. Scleral photographs of the temporal right eye were taken after administration of topical phenylephrine 10% at the indicated times in the study. Week 40 is four weeks following the last gevokizumab injection of the first extension phase. Week 52A represents the enrollment date of the second extension phase, which in this patient occurred 7.5 months after her last gevokizumab injection as part of the first extension phase. Week 62 represents the last time point for gevokizumab injection after receiving three injections at weeks 52A, 54, and 58.