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Conclusions

In patients with relapsing-remitting multiple sclerosis, fingolimod 0.5 mg and 1.25 mg once daily was superior to interferon beta-1a in improving relapse-related outcomes, including annualized relapse rates and proportion without relapse, over a 1 year period. Progression of disability was not different between the treatments. The higher dose (1.25 mg once daily) of fingolimod resulted in higher numbers and more severe adverse events, including herpes zoster infections and symptomatic bradycardia after the first dose, as well as more patients discontinuing treatment. Differences in adverse events between 0.5 mg fingolimod and interferon beta-1a were limited to more patients with pyrexia, myalgia, and flu-like symptoms with interferon and more with elevated liver enzymes with fingolimod. Ongoing concerns with the safety of fingolimod included the risk of macular edema, the effect of lung function, cancers, and serious viral infections. Further studies are underway to better determine the risk with fingolimod.

Summary

Overall, the strength of the evidence for the comparison of fingolimod 1.25 mg or 0.5 mg with interferon beta-1a was moderate for all relevant outcomes. These findings were based on a single study, however, and further studies, particularly longer studies or studies using a different interferon, may change the results. Strength of evidence was not evaluated for the durability of effect because it is not comparative. Nor was there evidence for direct comparison to any other interventions.

Results

Electronic literature searches identified 76 citations. We received a dossier from the pharmaceutical manufacturer, which supplied additional data on studies in the form of posters and slide sets from presentations at conferences. We reviewed the US Food and Drug Administration Medical and Statistical reviewer reports regarding the New Drug Application for fingolimod. By applying the eligibility criteria, we ultimately included 4 unique studies enrolling a combined 2845 patients: 1 head-to-head comparison trial, 2 placebo-controlled trials, and 1 randomized extension study of 1 placebo-controlled trial. The US Food and Drug Administration documents included some data on these studies. Two posters relating to an additional extension study of the head-to-head comparison trial submitted for consideration by the manufacturer were not included due to inadequate information provided to conduct a full quality assessment., All included studies enrolled patients with relapsing-remitting multiple sclerosis, except for 31 patients with secondary progressive multiple sclerosis enrolled in the first placebo-controlled trial. Appendix B shows list of excluded studies and reasons for exclusion at this stage. Figure 1 shows the flow of study selection.,

Introduction

In the Drug Effectiveness Review Project Report on Disease-modifying Drugs for Multiple Sclerosis, 5 injectable drugs were reviewed in comparison with each other (most recent update, August 2010). Since that time, an oral medication, fingolimod (Gilenya™) was approved in the United States and Canada for patients with relapsing forms of multiple sclerosis to reduce the frequency of clinical exacerbations and to delay the accumulation of physical disability. Fingolimod is a sphingosine 1-phosphate receptor modulator and is reported to work at least in part though reducing lymphocyte migration into the central nervous system. It is thought to result in redistribution of autoaggressive lymphocytes (T cells and B cells) to the lymph nodes and away from the central nervous system.

Evidence Tables

Oral fingolimod 1.25 mg qd

Methods

Adult outpatients with multiple sclerosis,

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