DX56
Short- and Long-Term Predictors of Relapses or Disability Worsening in Patients with Multiple Sclerosis in the Phase 3 TRANSFORMS Study
Objectives: To assess the ability of parameters at baseline and during TRANSFORMS to predict relapses or 6-month confirmed disability progression (6MCDP) in the short term and long term during the trial extension.
Methods: This was a post hoc analysis of the 36-month follow-up of TRANSFORMS, a 12-month, double-blind, randomized, phase 3 study of fingolimod 0.5 mg/day versus intramuscular (IM) interferon (IFN) beta-1a. On entering the extension, patients randomized to receive IFN beta-1a IM were switched to fingolimod. Unadjusted logistic regression assessed which parameters from baseline to month (M) 12 predicted clinical outcomes (relapses or 6MCDP, measured using the Expanded Disability Status Scale [EDSS]) during M12–24 and M12‒48.
Results: In total, 1292 patients were randomized in TRANSFORMS (M12–24, n=973; M12–48, n=778). Predictors of relapses in the short and long terms included the combination of MRI lesion activity (at least one gadolinium-enhancing lesion or at least two new T2 lesions) and at least one confirmed relapse (M12–24: odds ratio [OR] 2.776, 95% confidence interval [CI] 1.649–4.674, p<0.0001; M12–48: OR 3.703, 95% CI 2.158–6.356, p<0.0001), and the number of confirmed relapses during M0–12 (M12–24: OR 2.24, 95% CI 1.751–2.866, p<0.0001; M12–48: OR 2.297, 95% CI 1.753–3.009, p<0.0001). Predictors of 6MCDP during M12–48 included baseline EDSS score (OR 1.44, 95% CI 1.244–1.668, p<0.0001), duration of MS since diagnosis (OR 1.045, 95% CI 1.009–1.082, p=0.0131) and age (OR 1.033, 95% CI 1.010–1.057, p=0.005).
Conclusions: Relapse and MRI lesion activity in TRANSFORMS predicted relapses in the short and long terms; baseline EDSS score, age and disease duration predicted 6MCDP. These results suggest that early use of high-efficacy treatment may help to control disease worsening.