Fast track — ArticlesComparison of fingolimod with interferon beta-1a in relapsing-remitting multiple sclerosis: a randomised extension of the TRANSFORMS study
Introduction
Fingolimod is the first in a new class of drugs—the sphingosine 1-phosphate receptor modulators—and is approved for the treatment of relapsing multiple sclerosis at a recommended dose of 0·5 mg once daily. The efficacy of fingolimod in relapsing-remitting multiple sclerosis (RRMS) has been shown in a clinical programme that includes two large multicentre phase 3 studies: a 1-year active-controlled study, TRANSFORMS (trial assessing injectable interferon versus FTY720 oral in RRMS),1 in which fingolimod had better efficacy than a first-line treatment (intramuscular interferon beta-1a) on relapse and MRI outcomes, and a 2-year placebo-controlled study, FREEDOMS (FTY720 research evaluating effects of daily oral therapy in multiple sclerosis),2 that showed efficacy on relapses, disability progression, and MRI measures. We present results from the second year of TRANSFORMS, a 1-year extension in which patients originally randomly assigned to receive fingolimod continued with treatment at the same dose as in the core study, and patients originally assigned to receive interferon beta-1a in the core study were randomly reassigned to receive fingolimod 0·5 mg or 1·25 mg. We did within-group comparisons to assess the efficacy and safety of fingolimod during months 13–24 compared with months 0–12 in patients who had switched from interferon beta-1a at month 12. We compared groups of patients receiving fingolimod for up to 2 years with patients who switched treatment to assess the effect of delayed onset of fingolimod.
Section snippets
Participants
Patients eligible for inclusion in the core study: were aged 18–55 years; had a diagnosis of multiple sclerosis in accordance with the 2005 revised McDonald criteria,3 with a relapsing-remitting disease course; had one or more documented relapses in the year before randomisation or two or more documented relapses in the 2 years before randomisation; had an expanded disability status scale (EDSS) score of 0–5·5;4 and were neurologically stable, with no evidence of relapse or corticosteroid
Results
1123 (87%) of 1292 patients completed the core study on a study drug.1 1027 (92%) of the 1123 patients entered our extension and received study drugs, and 882 (86%) of these patients completed 24 months of treatment (figure 1). Baseline demographics and disease characteristics for the eITT population were similar across all treatment groups (table 1), and were consistent with those of the core ITT population.1 Completion rates were slightly higher for patients who received continuous treatment
Discussion
Our findings show that, in patients with RRMS, there were improvements in clinical and MRI measures of efficacy after switching from interferon beta-1a to fingolimod without the emergence of unexpected adverse events. Patients who received continuous fingolimod had reduced relapse rates and MRI lesion activity over 2 years relative to patients who received interferon beta-1a during the first year and fingolimod during the second year. We did not identify a loss of efficacy during months 13–24
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