Uveitis in Patients with Multiple Sclerosis in Clinical Trials of Fingolimod: Incidence, Prevalence, and Impact on Disease Course

Abstract

To determine the incidence and prevalence of uveitis and its effect on multiple sclerosis (MS) disease activity and outcomes in patients with MS who participated in the fingolimod clinical trial program. Analysis of pooled data (N= 27 528) from patients enrolled in fingolimod clinical studies and their extensions. Patients were stratified into 4 cohorts based on the history of uveitis at baseline and uveitis events during the observation period: no history and no uveitis events ("no uveitis"); history and no uveitis events ("history"); no history and uveitis events ("first event"); history and uveitis events ("recurrent event"). Adult patients diagnosed with relapsing or primary progressive MS. Patients received fingolimod (0.5, 1.25, or 5 mg/day), placebo, or intramuscular interferon beta-1a (IFNβ-1a IM) during the core studies; patients receiving placebo or IFNβ-1a IM were switched to fingolimod 0.5mg therapy for study extensions. Incidence and prevalence of uveitis, and MS outcome measures, including annualized relapse rate (ARR), time to first relapse, change in Expanded Disability Status Scale (EDSS) score from baseline, and proportion of patients with 6-month confirmed disability progression. A total of 189 patients in the analysis population had uveitis. Of these, 162 patients had a history of uveitis (prevalence, 0.59%). Uveitis occurred as a first event in 27 patients (incidence, 0.1 per 100 patient-years) and as a recurrent event in 10 of 162 patients (prevalence, 6.17%). Patients with uveitis had a significantly shorter time to first relapse (mean, 2.11 vs. 8.12 years; P= 0.047) and a significantly higher ARR (0.31 vs. 0.21; P= 0.025) than those without uveitis. Mean increase in EDSS score at month 120 and the proportions of patients with 6-month confirmed disability progression, and with EDSS score ≥4 during follow-up, were similar in patients with uveitis compared with those without uveitis. This pooled analysis involving a large patient cohort showed that patients with MS and uveitis had increased MS relapse activity compared with those without uveitis.