Relapse Outcomes in Patients with Multiple Sclerosis Treated with Fingolimod: Subgroup Analyses of Three Phase 3 Fingolimod Trials

Background: In phase 3 clinical trials, fingolimod significantly reduced annualized relapse rates (ARRs) in patients with relapsing–remitting multiple sclerosis (RRMS) in comparison with placebo and intramuscular interferon (IFN) β-1a. This post hoc subgroup analysis of pooled data from the FREEDOMS, FREEDOMS II, and TRANSFORMS patient populations investigated whether the beneficial treatment effect reported for the overall population was consistent in subgroups of patients with different baseline characteristics.

Objectives: To report the effects of oral fingolimod treatment on ARRs in subgroups of patients with RRMS.

Methods: Subgroups were defined by demographic factors (sex and age), disease characteristics (baseline disability scores, relapse rates, and lesion parameters), and previous therapy. ARRs were estimated using a negative binomial regression model adjusted for study. Logarithmic time on study was used as the offset variable to account for the varying lengths of time that patients spent in each study. Subgroup analyses were performed using data from the intention-to-treat populations pooled for all three trials (N = 3635).

Results: Compared with placebo and IFNβ-1a, treatment with fingolimod 0.5 mg was associated with significantly lower ARRs in all subgroups (relative reduction: 23–64%) except for the subgroup older than 40 years receiving IFN (P = .230) and men receiving IFN (P = .081). ARR ratios ranged from 0.36 (95% CI: 0.30–0.45; P < .001) relative to placebo in patients aged 40 years or younger to 0.77 (95% CI: 0.50–1.18; P = .230) relative to IFN in patients older than 40 years.

Conclusions: Fingolimod 0.5 mg demonstrated consistent efficacy benefits over placebo in patients with RRMS irrespective of baseline demographic status, disease activity, and disease severity. The efficacy benefits of fingolimod 0.5 mg over IFNβ-1a were dependent on age and sex.