Grosskreutz, Cynthia, Hockey, Hans-Ulrich, Serra, Denise and Dryja, Ted (2015) Dry eye signs and symptoms persist during systemic neutralization of IL-1β by canakinumab or IL-17A by secukinumab. Cornea, 34 (12). pp. 1551-1556.

Abstract

Objective: To evaluate whether inhibition of the pro-inflammatory cytokines IL-1β or IL-17A by canakinumab or secukinumab, respectively, influence the signs and symptoms of dry eye.
Design: A double-masked, placebo-controlled, outpatient clinical trial.
Participants: Seventy-two patients with moderate to severe dry eye.
Methods: Patients were randomized in a 1:1:1 ratio to the following three treatments: a single intravenous dose of canakinumab that neutralizes IL-1β, a single intravenous dose of secukinumab that neutralizes IL-17A, or an intravenous dose of placebo. The signs and symptoms of dry eye were evaluated on the treatment day and 1 week, 4 weeks, and 8 weeks after the treatment.
Main Outcome Measures: The pre-specified primary efficacy endpoint was corneal staining in the study eye as measured by the NEI staining score 4 weeks after treatment. Secondary endpoints at that visit and 1 week and 8 weeks after treatment included tear production (Schirmer test), tear film breakup time, conjunctival redness, the ocular surface disease index (OSDI), the frequency of a desire for a topical ocular lubricant, and visual acuity.
Results: Of the 71 patients included in the analysis of safety, the rate of adverse events was similar between treatment groups; in particular, there was no noteworthy excess of adverse events in the canakinumab and secukinumab groups compared with the placebo group. Sixty-nine patients appropriately completed the study and were included in the analyses of efficacy. The course of corneal staining scores from baseline to four weeks, respectively, were for canakinumab 1.46 to 1.33 (p = 0.62 compared to placebo), for secukinumab 1.46 to 1.23 (p = 0.22), and for placebo 1.68 to 1.42. There were no changes in the other measures of efficacy beyond what was within the range expected for stochastic day-to-day variation.
Conclusions: Neither canakinumab nor secukinumab substantially improved the corneal staining score (the primary endpoint) or improved the other measures of the severity of dry eye. The results suggest that the inhibition of IL-1β or IL-17A obtained by systemic administration of neutralizing drugs does not influence the severity of dry eye.

Item Type:	Article
Date Deposited:	26 Apr 2016 23:45
Last Modified:	26 Apr 2016 23:45
URI:	https://oak.novartis.com/id/eprint/26106