Effect of Switching from Intramuscular Interferon b-1a to Fingolimod on Time to Relapse in Patients with Relapsing-Remitting Multiple Sclerosis Enrolled in a 1-Year Extension of TRANSFORMS (P07.107)

OBJECTIVE: To compare the observed time to first confirmed relapse after switching from intramuscular (IM) interferon (IFN) b-1a IM to fingolimod with the estimated time to first relapse had the patient remained on IFNb-1a IM. BACKGROUND: In TRANSFORMS, a 12-month, phase 3, randomized, double-blind trial, oral fingolimod 0.5 or 1.25 mg significantly reduced the annualized relapse rate (ARR) by 52% and 38%, respectively, compared with IFNb-1a IM 30 μg once weekly in patients with relapsing-remitting multiple sclerosis (RRMS). In a 1-year extension, IFNb-1a IM patients were re-randomized to fingolimod 0.5 or 1.25 mg; ARR was reduced by 30% and 36%, respectively, compared with the previous 12 months. DESIGN/METHODS: The analysis included patients who switched from IFNb-1a IM to fingolimod during the extension (intent-to-treat). The Branson and Whitehead switch model (Branson M and Whitehead J. Stats Med . 2002;21:2449-2463) was used to estimate the ratio of the observed time to first confirmed relapse to the estimated time to first relapse if the patient had remained on IFN b-1a IM. Ratios >1 (greater time to relapse) show a benefit of switching to fingolimod. RESULTS: Of 431 patients who received IFNb-1a IM in the original trial, 341 entered the extension; 167 switched to fingolimod 0.5 mg and 174 switched to fingolimod 1.25 mg. Overall, 31 patients had a relapse after switching. The estimated ratio of observed time to relapse vs estimated time was 2.09 (95% CI, 1.45–3.04; n=16) for the IFNb-1a IM to fingolimod 0.5 mg switch group and 1.84 (95% CI, 1.30–2.65; n=15) for the IFNb-1a IM to fingolimod 1.25 mg switch group. CONCLUSIONS: Observed time to first confirmed relapse after switching from IFNβ-1a IM to fingolimod was approximately 2-fold longer than the estimated time to relapse had patients remained on IFNβ-1a IM, complementing previous findings suggesting the benefit of switching. Supported by: Novartis Pharmaceuticals Corporation. Disclosure: Dr. Meng has received personal compensation for activities with Novartis. Dr. Meng holds stock and/or stock options in Novartis. Dr. Cutter has received personal compensation for activities with Sanofi-Aventis Pharmaceuticals, Inc., Cleveland Clinic, Daichi-Sankyo, GlaxoSmithKline Inc., Genmab Biopharmaceuticals, Eli Lilly & Company, Medivation, and Modigenetech. Dr. Cutter has received compensation for serving as the president of Pythagoras, INC. Dr. Cutter has received research support from various pharmaceutical corporations. Dr. Chin has received personal compensation for activities with Novartis. Dr. Chin holds stock and/or stock options in Novartis. Dr. Hashmonay has received personal compensation for activities with Novartis as an employee. Dr. Hashmonay holds stock and/or stock options in Novartis. Dr. Islam has received personal compensation for activities with Novartis as an employee. Dr. Islam holds stock and/or stock options in Novartis.