The TRANSFORMS trial: Fingolimod vs interferon in multiple sclerosis [Classics Series]

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1. Fingolimod significantly reduced the number of relapses as compared to interferon beta-1a over a one-year period.

2. Fingolimod was associated with more transient bradycardia and a higher infection rate as compared to interferon.

Original Date of Publication: February 4, 2010

Study Rundown: In summary, patients treated with fingolimod (1.25 mg or 0.5 mg) experienced significant lower annualized relapse rates as compared to those treated with interferon beta-1a in this phase 3 study (P<0.001 for both comparisons). These findings were supported by fingolimod patients having significantly fewer new or enlarging hyperintense lesions on T2-weighted magnetic resonance imaging than patients in the interferon group. The study also demonstrated dose-dependent increases in the incidence of bradycardia and atrioventricular block with fingolimod treatment. The one-year study duration limits assessment of the long-term safety and multiple sclerosis (MS) relapse outcomes, thus longer studies are needed. While it was hoped that oral medications for MS would improve compliance, this trial found higher rates of drug discontinuation with fingolimod, compared to interferon. Notably, the TRANSFORMS trial was supported by Novartis Pharma.

Please click to read study in NEJM

In-Depth [randomized, controlled study]: Originally published in 2010, the TRANSFORMS trial assessed the efficacy and safety of oral fingolimod, a sphingosine-1-phosphate-receptor modulator, compared to intramuscular interferon beta-1a in relapsing-remitting MS over a 12-month period. A total of 1,292 patients underwent randomization to receive fingolimod 1.25 mg daily, fingolimod 0.5 mg daily, or 30 µg of IM interferon beta-1a weekly.

The annualized relapse rates were 0.20 (95%CI 0.16-0.26) and 0.16 (95%CI 0.12- 0.21) for fingolimod 1.25 mg and 0.5 mg, respectively, compared to a rate of 0.33 (95%CI 0.26-0.42) for interferon beta-1a. The difference between fingolimod and interferon was significant (P<0.001) for both doses. A higher percentage of adverse events leading to drug discontinuation occurred in the high-dose fingolimod group, with a 10% discontinuation rate, versus 5.6% for the 0.5 mg fingolimod group and 3.7% for the interferon beta-1a group.

By Jose-Marc Techner, Andrew Cheung, M.D.

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