Disease Activity in the First Year Predicts Clinical Outcomes in Patients with Multiple Sclerosis in the Phase 3 Freedoms and Freedoms II Studies

Background: Magnetic resonance imaging (MRI) lesion activity and/or relapses occurring early in the course of multiple sclerosis (MS) have been proposed as predictors of long-term clinical outcomes.

Objectives: To assess whether MRI disease activity and/or relapses during the first 12 months of the FREEDOMS and FREEDOMS II studies predicted long-term clinical outcomes (relapses and 6-month confirmed disability progression [CDP]).

Methods: This post hoc analysis used pooled data from the FREEDOMS and FREEDOMS II studies, in which patients were randomized to receive either oral fingolimod (0.5 mg or 1.25 mg) or placebo once daily. On entering the extension phases, patients were switched from placebo to fingolimod 0.5 mg. Unadjusted logistic regression was used to assess the ability of MRI disease activity (defined as one or more T1 Gd-enhancing lesions or two or more T2 lesions) and/or one or more relapses occurring during months 0‒12 of treatment to predict the likelihood of clinical outcomes (relapses or 6-month CDP as measured by the Expanded Disability Status Scale [EDSS]) in months 12–24 and months 12‒48.

Results: A total of 2355 patients were randomized in FREEDOMS and FREEDOMS II, with 1693 patients entering the extension phases. During months 0‒12, MRI disease activity or relapses alone were significantly predictive of relapses and 6-month CDP, both during months 12‒24 (relapses: odds ratio [OR] 1.787, 95% confidence interval [CI] 1.420–2.248, P < .0001; 6-month CDP: OR 2.367, 95% CI 1.990–2.815, P < .0001) and during months 12‒48 (relapses: OR 1.505, 95% CI 1.179–1.922, P = .0010; 6-month CDP: OR 2.812, 95% CI 2.182–3.623, P < .0001). Adding relapses to MRI activity improved predictive ability further (months 12‒24: OR 3.285, 95% CI 2.454–4.397, P < .0001; months 12‒48: OR 2.953, 95% CI 2.022–4.312, P < .0001).

Conclusions: In the pooled FREEDOMS and FREEDOMS II population, MRI disease activity or relapses alone were predictors of both shorter-term (months 12‒24) and longer-term (months 12‒48) clinical disease activity. The combination of MRI disease activity and relapses also effectively predicted future relapses and disability progression.