1184: Does Blocking IL-17 Treat Recalcitrant Uveitis? Explorative Study on the Use of Ixekizumab to Manage Patients with Uveitis.

Background/Purpose: Non-infectious uveitis can exist as a primary autoimmune disease or can be a manifestation of an underlying systemic illness. Despite the availability of new therapies, there are few medications approved for the management of uveitis. The purpose of this study was to determine the efficacy and safety of Ixekizumab, an IL-17A targeting human monoclonal antibody in patients with recalcitrant non-infectious intermediate, posterior, panuveitis, or chronic steroid-dependent anterior noninfectious uveitis.

Methods: This was a 24-week prospective, open-label, proof-of-concept exploratory study. The study was designed with two treatment arms of Ixekizumab. Both arms were treated at Week 0 with a loading dose of 160mg of Ixekizumab. Subjects in Arm 1 were then treated with biweekly dosing of 80mg SC Ixekizumab. Subjects in Arm 2 were assigned to a regimen of 80mg SC every four weeks. All subjects began an oral steroid taper starting with 60mg of prednisone alongside the loading dose at Week 0.


Primary Endpoint: A four-point composite endpoint was used to evaluate for visual acuity, control of inflammation, tapering of medication therapy and cystoid macular edema, scored “yes/no” (Suhler et. al., 2013). Control of inflammation was defined as either achieving clinical quiescence, referring to anterior chamber cells and flare of 0.5+ or less as well as vitreous haze of 0.5+ or less, or by achieving a greater than two step reduction in both AC cells and flare.
Secondary Endpoints: The NEI VFQ-25 questionnaire was utilized to gain a standardized insight on each patient’s subjective visual functioning throughout each timepoint of the trial, with a higher score indicating better function and lesser impact of visual impairment from uveitis on daily life. Intraocular pressure was monitored for changes, as one goal for the use of steroid-sparing immunomodulatory therapy for patients with uveitis is to avoid steroid-induced ocular hypertension.




Results: The trial was closed to recruitment prematurely due to an overall lack of clinical response. Only two participants completed the entire duration of the study without being discontinued from Ixekizumab and/or without receiving additional rescue therapy. All other subjects required rescue therapy between Week 8 and Week 20. Additionally, all patients in Arm 2 assigned to a maintenance dose of Ixekizumab dosing every 4 weeks, were reassigned to Arm 1 due to inadequate clinical response to Q 4 week dosing.

Conclusion: In this study, the efficacy of Ixekizumab for the management of recalcitrant uveitis was explored. None of the nine subjects enrolled met the criteria for clinical response, and all but two patients necessitated rescue therapy and/or discontinuation of the investigational treatment. The lack of efficacy resulted in early study termination.

There are a number of potential explanations for the lack of response. The first is that IL-17A may not be the effector cytokine target in the patients studied. This population was clinically heterogeneous both in terms of the uveitis studied and underlying disease. It is possible that the dose of therapy utilized was suboptimal. Lastly, the number of patients may have been insufficient to detect a statistically benefit.