Relapse rates in patients with multiple sclerosis treated with fingolimod: Subgroup analyses of pooled data from three phase 3 trials.

Background: Fingolimod is a once-daily, orally administered therapy for relapsing forms of MS. It has been shown to reduce relapse rates significantly in all phase II and phase III clinical trials when compared with placebo and intramuscular interferon β-1a (IFNβ-1a IM).

Methods: This study compared annualized relapse rates (ARRs) associated with fingolimod, placebo and IFNβ-1a IM, in patient subgroups from the pooled FREEDOMS, FREEDOMS II, and TRANSFORMS populations. This provided a large data set in which the efficacy of fingolimod could be assessed across a range of patient subgroups, including clinically relevant subgroups not previously analysed.

Results: Compared with placebo, fingolimod was associated with significantly lower ARRs across all patient subgroups with relative reductions in ARRs ranging from 35% (patients who had previously received treatment for their MS for up to 1 year; P<0.05) to 69% (patients with symptoms for less than 3 years before study entry; P<0.001). Other relative reductions in ARR compared with placebo included 64% in patients aged 40 years or younger and 63% in those naïve to treatment (P<0.001 for both). Compared with IFNβ-1a IM, the greatest benefits to ARR were seen in patients aged 40 years or younger (55% relative ARR reduction, P<0.001) and in a small subgroup of patients who had previously received IFNβ and glatiramer acetate (55% relative ARR reduction; P<0.05). Reductions in ARR compared with IFNβ-1a IM were not statistically significant in men (33%, P=0.081), in patients aged over 40 years (23%, P=0.230) and in those who had received treatment prior to the study for 1 year or less (35%, P=0.108). Fingolimod was associated with significantly lower ARRs compared with placebo and with IFNβ-1a IM irrespective of treatment status (treatment-naïve and previously treated for MS), and regardless of type of previous therapy.

Conclusions: Fingolimod provided consistent efficacy benefits over placebo and IFNβ-1a IM across a range of subgroups of patients with relapsing MS. The magnitude of the beneficial effect of fingolimod over IFNβ-1a IM may depend on age, sex, and duration of previous treatment. These findings suggest that most benefit will be gained by patients who start fingolimod early in the disease course, but the findings also suggest that fingolimod treatment will benefit patients later in the disease course when they have already accrued disability.