Treatment of Noninfectious Uveitis with Secukinumab
The results of three multicenter, randomized, double-masked,
placebo-controlled, dose-ranging Phase III studies (SHIEDL, INSURE and ENDURE) were reviewed
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.
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.
After an initial subcutaneous (s.c.) loading phase in each treatment arm, patients received
s.c. maintenance therapy with secukinumab 300 mg every two 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 were a reduction of
uveitis recurrence or vitreous haze score during withdrawal of concomitant immunosuppressive
medication (ISM). Other endpoints included best-corrected visual acuity, ISM use (expressed as
a standardized ISM score) and safety outcomes.
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. It was
reported that overall, there was no loss in visual acuity reported in any treatment group during
follow-up in all three 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 three studies.
The primary efficacy endpoints of the three studies were not met. The secondary efficacy data from
these studies suggest a beneficial effect of secukinumab in reducing the use of concomitant ISM.