The Effect of Fingolimod on Four Measures of Disease Activity in Patients with Relapsing–Remitting Multiple Sclerosis: A Meta-Analysis of the Phase 3 Freedoms Trials
Objectives: To determine the consistency of the treatment effect of fingolimod across the 2-year, randomized, placebo-controlled FREEDOMS and FREEDOMS II trials in patients with RRMS.
Methods: The post-hoc analysis included the intent-to-treat populations from FREEDOMS and FREEDOMS II; results are reported for fingolimod 0.5 mg (approved dose (N=783) vs placebo (N=773). Both ARR and new/enlarging T2 lesions were analyzed using negative binomial regression, BVL in an analysis of covariance, and CDP (confirmed at 6 months) with a Cox proportional hazards model; CDP was an increase in EDSS score of ≥1.5 if score at baseline (BL)=0, of ≥1.0 if BL=0.5–5.0, and of ≥0.5 if BL≥5.5. All statistical models included a treatment-by-study interaction.
Results: Compared with placebo in the pooled population, fingolimod 0.5 mg was associated with a 52% reduction in ARR (ratio [95%CI]: 0.48 [0.41–0.56]; p<0.0001), 76% reduction in new/enlarging T2 lesions (ratio [95%CI]: 0.24 [0.20–0.29]; p<0.0001), 33% reduction in the rate of BVL (respectively, 0.71 vs 0.48%/year; least-squares mean difference [95%CI]: 0.23 [0.13–0.33]; p<0.0001), and 39% reduction in the risk of CDP (hazard ratio [95%CI]: 0.61 [0.46–0.81]; p=0.0006). For all four endpoints, the treatment effect was consistent between the two studies (no significant treatment-by-study interaction).
Conclusions: Fingolimod was associated with a consistent, significant reduction in disease activity across key measures of inflammatory processes and disease worsening in patients with RRMS.