Elsevier

Ophthalmology

Volume 120, Issue 4, April 2013, Pages 777-787
Ophthalmology

Original article
Secukinumab in the Treatment of Noninfectious Uveitis: Results of Three Randomized, Controlled Clinical Trials

https://doi.org/10.1016/j.ophtha.2012.09.040Get rights and content

Purpose

To determine the efficacy and safety of different doses of secukinumab, a fully human monoclonal antibody for targeted interleukin-17A blockade, in patients with noninfectious uveitis.

Design

Three multicenter, randomized, double-masked, placebo-controlled, dose-ranging phase III studies: SHIELD, INSURE, and ENDURE.

Participants

A total of 118 patients with Behçet's uveitis (SHIELD study); 31 patients with active, noninfectious, non–Behçet's uveitis (INSURE study); and 125 patients with quiescent, noninfectious, non–Behçet's uveitis (ENDURE study) were enrolled.

Methods

After an initial subcutaneous (s.c.) loading phase in each treatment arm, patients received s.c. maintenance therapy with secukinumab 300 mg every 2 weeks (q2w), secukinumab 300 mg monthly (q4w), or placebo in the SHIELD study; secukinumab 300 mg q2w, secukinumab 300 mg q4w, secukinumab 150 mg q4w, or placebo in the INSURE study; or secukinumab 300 mg q2w, secukinumab 300 mg q4w, secukinumab 150 mg q4w, or placebo in the ENDURE study.

Main Outcome Measures

Reduction of uveitis recurrence or vitreous haze score during withdrawal of concomitant immunosuppressive medication (ISM). Other end points included best-corrected visual acuity, ISM use (expressed as a standardized ISM score), and safety outcomes.

Results

After completion or early termination of each trial, there were no statistically significant differences in uveitis recurrence between the secukinumab treatment groups and placebo groups in any study. Secukinumab was associated with a significant reduction in mean total post-baseline ISM score (P = 0.019; 300 mg q4w vs. placebo) in the SHIELD study. Likewise, secukinumab was associated with a greater median reduction in ISM score versus placebo in the INSURE study, although no statistical analysis of the difference was conducted because of the small sample size. Overall, there was no loss in visual acuity reported in any treatment group during follow-up in all 3 studies. According to descriptive safety statistics, the frequencies of ocular and nonocular adverse events seemed to be slightly higher among secukinumab groups versus placebo across the 3 studies.

Conclusions

The primary efficacy end points of the 3 studies were not met. The secondary efficacy data from these studies suggest a beneficial effect of secukinumab in reducing the use of concomitant ISM.

Financial Disclosure(s)

Proprietary or commercial disclosure may be found after the references.

Section snippets

Study Design and Patient Population

All of the studies were randomized, placebo-controlled, and double-masked, with study investigators and participants masked to treatment assignments. Informed consent was obtained from all patients in each study. Approvals from the institutional review boards at the participating centers were obtained, and the studies were conducted in accordance with the principles of the Declaration of Helsinki. The study details were registered on ClinicalTrials.gov (NCT00995709 [SHIELD], NCT01095250

Patient Demographics and Baseline Characteristics

In the SHIELD study, the majority of patients were male and aged <40 years. No major differences among treatment groups were observed with respect to demographics or baseline characteristics (Table 1, available at http://aaojournal.org). A total of 118 patients were randomized, of whom 97 (82.2%) completed the study and 21 (17.8%) discontinued the study. The most common reasons for discontinuation were AEs in the secukinumab 300 mg q2w group (n = 4, 10.3%), withdrawn consent in the secukinumab

Discussion

In 2010, Hueber et al23 reported that secukinumab demonstrated efficacy and safety in 16 patients with active chronic noninfectious uveitis who participated in an open-label proof-of-concept clinical study. In that study, disease severity in the participants with uveitis was comparable to that in a study of infliximab, an antibody to tumor necrosis factor-alpha (TNF-α), suggesting that inhibition of IL-17A also could be a valid therapeutic approach that warranted further investigation in

Acknowledgments

Manuscript writing was provided by Rupendra Jadhav and Damanjeet Ghai of Novartis Pharma AG. Editorial review was provided by Kalyan Pulipaka of Novartis Pharma AG and by Eric Justice and Andrew Horgan of BioScience Communications, New York, New York (supported by Novartis Pharma).

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    Manuscript no. 2012-1018.

    Financial Disclosure(s): The author(s) have made the following disclosure(s): ADD has received compensation from Novartis for consultancy and work related to the conduct of the studies reported. ADD has also received research grants from Novartis. IT-T has received compensation from Novartis for travel, meetings, and accommodations related to the studies reported and other activities. SF has received compensation from Novartis for consultancy. SF has also received research grants from Novartis. M.Z. and S.A. have no financial relationships with Novartis. SHML and VB are employees of Novartis. Clinical trials.gov registration numbers: NCT00995709 (SHIELD), NCT01095250 (INSURE), and NCT01032915 (ENDURE).

    The sponsor participated in the design of each study, conducting each study, data collection, data management, data analysis, interpretation of the data, and preparation and review of the manuscript.

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