Disease Activity during the First Year Predicts Clinical Long-Term Outcomes in Patients with Multiple Sclerosis: Fingolimod Treatment Benefit

Background: Early magnetic resonance imaging (MRI) activity and/or relapses have been explored for their ability to predict long-term clinical outcomes in patients with relapsing forms of multiple sclerosis (MS).

Objectives: To assess whether MRI activity and/or relapses during the first 12 months of TRANSFORMS predicted later clinical outcomes, and to assess clinical outcomes in patients who switched from intramuscular (IM) interferon (IFN) beta-1a to oral fingolimod after 12 months.

Methods: This is a post hocanalysis of the 36-month follow-up of TRANSFORMS, a double-blind, randomized, phase 3 study of fingolimod (0.5 mg or 1.25 mg daily) versus IFN beta-1a IM (30 μg weekly). On entering the extension, patients randomized to IFN beta-1a IM were re-randomized to either fingolimod 0.5 mg or 1.25 mg (switch group). Unadjusted logistic regression was used to assess whether MRI activity (defined as one or more T1 Gd-enhancing lesions or two or more T2 lesions) and/or one or more relapses during months 0‒12 of treatment predicted relapses or 6-month confirmed disability progression (CDP) as measured by Expanded Disability Status Scale [EDSS]) at months 12‒24 and 12‒48.

Results: In total, 1292 patients were randomized in the core phase, with 1030 (79.7%) entering the extension phase. MRI activity in the first year was predictive of relapses or 6-month CDP (months 12‒24: odds ratio [OR] 1.359, 95% confidence interval [CI] 0.958‒1.926, P = .0851; months 12‒48: OR 1.701, 95% CI 1.246‒2.322, P = .0008). Relapses in the first year were also predictive of relapses or 6-month CDP (months 12‒24: OR 2.096, 95% CI 1.654‒2.655, P < .0001; months 12‒48: OR 2.008, 95% CI 1.541‒2.616, P < .0001). Additionally, combined MRI activity and relapses in the first year were predictive of relapses or 6-month CDP (months 12‒24: OR 2.695, 95% CI 1.643‒4.420, P < .0001; months 12‒48: OR 3.030, 95% CI 1.761‒5.212, P < .0001). The proportions of patients with MRI activity and/or relapses during months 0‒12 was 4.9% for fingolimod 0.5 mg and 12.9% for IFN; at months 12‒24, the proportion for continuous fingolimod remained low (3.2%) while the proportion in patients who switched from IFN to fingolimod decreased to 3.9%.

Conclusions: MRI activity and/or relapses during the first year of TRANSFORMS were predictors of later clinical outcomes. Switching from IFN beta-1a to fingolimod after 12-months reduced the proportion of patients experiencing later MRI activity and relapses.