OBJECTIVE: To review the evidence supporting the European Union marketing authorization of drugs for multiple sclerosis (MS) and assess how far postmarketing research addresses information gaps at the time of approval.
METHODS: Through its database, we identified drugs approved by the European Medicines Agency and gathered data on pivotal trials from the European Public Assessment Reports and corresponding publications. We searched Medline, Embase, Cochrane Library, and trial registries for postmarketing randomized controlled trials testing the drugs identified in any form of the disease.
RESULTS: Since approval of interferon and glatiramer up to 2017, the Agency has examined 10 drugs for the treatment of MS, and 8 were included in this study: alemtuzumab, daclizumab, dimethyl fumarate, fampridine, fingolimod, peginterferon-β-1a, natalizumab, and teriflunomide. We analyzed 16 pivotal trials enrolling almost 16,000 participants. Eleven compared new drugs to placebo, 5 to interferon-β-1a. Annualized relapse rate was the primary outcome in two-thirds and coprimary with disability progression in the 2 studies of alemtuzumab. Of the 52 postmarketing trials, 24 reported final results and 28 were ongoing, terminated, or completed but no results were available. None directly compared the approved drugs, thus leaving their respective therapeutic values unknown. Data on the prevention of disease progression were scarce: none of the disease-modifying drugs showed any effect on disability progression.
CONCLUSION: The lack of comparative evidence and data on clinical effectiveness hamper the assessment of therapeutic value and place in therapy of drugs approved for MS.