Disability improvement as a clinically relevant outcome in clinical trials of relapsing forms of multiple sclerosis.

Abstract

BACKGROUND\nDisease-modifying therapies (DMTs) can reduce the risk of disability worsening in patients with relapsing forms of multiple sclerosis (RMS). High-efficacy DMTs can lead to confirmed or sustained disability improvement (CDI and SDI).\n\n\nOBJECTIVE AND METHODS\nPost hoc analyses of data from the TRANSFORMS, FREEDOMS, and FREEDOMS II trials and their extensions assessed the effects of fingolimod (0.5-1.25\u2009mg/day) on stabilizing or improving disability over ⩽8\u2009years in participants with RMS. CDI and SDI rates were compared between participants initially randomized to fingolimod, interferon (IFNβ-1a), or placebo.\n\n\nRESULTS\nAt 8\u2009years follow-up in TRANSFORMS, 35.1% (95% confidence interval [CI], 28.2%-43.1%) of assessed participants in the IFNβ-1a-fingolimod switch group and 41.9% (36.6%-47.6%) on continuous fingolimod experienced CDI; disability did not worsen in approximately 70%. Similar results were seen in the combined FREEDOMS population. Proportionally fewer TRANSFORMS participants achieved SDI in the IFNβ-1a-fingolimod switch group than on continuous fingolimod (5.4% [3.0%-9.5%] vs 14.2% [10.8%-18.4%], p\u2009=\u20090.01).\n\n\nCONCLUSION\nCDI and SDI are outcomes of interest for clinical trials and for long-term follow-up of participants with RMS. Monitoring CDI and SDI in addition to disability worsening may facilitate understanding of the therapeutic benefit of RMS treatments.