Fingolimod Reduces Likelihood and Severity of Relapse in MS Patients

Honolulu—An analysis of data from two phase 3 studies, presented at a poster session during the AAN meeting, found oral fingolimod more effective at preventing relapse in patients with multiple sclerosis (MS) than interferon beta-1a or placebo. Fingolimod, a US Food and Drug Administration–approved sphingosine 1-phosphate receptor modulator, was also associated with a >50% reduction in the incidences of severe relapse, relapse that impairs daily living, relapse necessitating steroid treatment, and relapse requiring hospitalization. The poster was titled Effect of Fingolimod on Severe Multiple Sclerosis Relapses, Healthcare Utilization, and Recovery: Results from Two Phase 3 Studies, TRANSFORMS and FREEDOMS. To arrive at these conclusions, the researchers evaluated findings from the TRANSFORMS (Trial Assessing Injectable Interferon vs FTY720 Oral in RRMS) and FREEDOMS (FTY720 Research Evaluating Effects of Daily Oral Therapy in Multiple Sclerosis) trials published last year in the New England Journal of Medicine [2010;362(5):402-415 and 387-401]. Using an approximate 1:1:1 ratio, the TRANSFORMS study (n=1280) randomized adults with MS to a 0.5-mg or 1.25-mg daily dose of fingolimod or to a 30-mcg dose of interferon beta-1a administered as a once-weekly intramuscular injection for 1 year. The randomized FREEDOMS trial (n=1272) used the same regimens of fingolimod with placebo as a comparator and continued treatment for 2 years. Both studies required participants to have a relapsing-remitting course of MS, with ≥1 confirmed relapse in the prior year or ≥2 confirmed relapses within the past 2 years. Individuals with Expanded Disability Status Scale scores >5.5 were ineligible, as was anyone who suffered a relapse or received steroid treatment within 30 days of randomization. In both studies, patient and disease characteristics were comparable among all groups. Looking at TRANSFORMS, the interferon beta-1a (n=431) group had 179 relapses compared with 89 in the fingolimod 0.5-mg group (n=429) and 105 in the fingolimod 1.25-mg group (n=420). The FREEDOMS trial’s placebo group (n=418) also had a significantly greater number of relapses (n=359) compared with the fingolimod 0.5-mg (n=425) and 1.25-mg (n=429) groups, which documented 172 and 148 relapses, respectively. In addition to recording the number of relapses, trial investigators assessed each incident’s severity and the subsequent level of recovery. For the subset of patients who relapsed, those assigned to interferon beta-1a, placebo, or fingolimod 1.25 mg were significantly more likely to have a severe relapse than patients randomized to fingolimod 0.5 mg. A post hoc analysis of adjusted data for the intent-to-treat population of TRANSFORMS estimated an annualized relapse rate (ARR) for severe relapse of 0.068 for patients treated with interferon beta-1a compared with 0.022 for patients receiving fingolimod 0.5 mg (P<.01) and 0.042 for patients given fingolimod 1.25 mg. In TRANSFORMS, fingolimod 0.5 mg was also associated with the lowest annualized rates of relapse-associated steroid use and hospitalization, relapse affecting daily activities, and incomplete recovery after relapse. Across all these measures, FREEDOMS investigators calculated notably higher ARRs with placebo and comparable ARRs between the different fingolimod doses, with ARRs for severe relapse and relapses with incomplete recovery slightly favoring the 0.5-mg dose. The poster authors highlighted a 2003 report that showed a mean of $12,870 in healthcare costs to treat an MS patient for severe relapse requiring a high level of intervention (eg, steroid treatment, hospitalization, postdischarge home healthcare). They noted that fingolimod 0.5 mg significantly decreased the risk of relapse; those that did occur were less likely to be severe, reducing the need for steroids or hospital stays. “Given the significant impact on patients and the direct and indirect costs associated with relapses, these results are likely to have important implications for patients and healthcare systems,” the authors concluded. This study was supported by Novartis Pharma AG, Basel, Switzerland; Novartis employees are included among the poster’s authors.