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Long-term Follow-up of the Safety of Delayed-Release Dimethyl Fumarate in RRMS: Interim Results from the ENDORSE Extension Study. (P7.235)

2015; Lippincott Williams & Wilkins; Volume: 84; Issue: 14_supplement Linguagem: Inglês

10.1212/wnl.84.14_supplement.p7.235

1526-632X

Carlo Pozzilli, J. Theodore Phillips, Robert J. Fox, Krzysztof Selmaj, Ray Zhang, Mark Novas, Marianne T. Sweetser, Ralf Gold,

Multiple Sclerosis Research Studies

OBJECTIVE: To report safety outcomes from ENDORSE, investigating long-term effects of delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF) in patients with relapsing-remitting multiple sclerosis (RRMS). BACKGROUND: DMF demonstrated broad efficacy and an acceptable safety profile in the Phase 3 DEFINE/CONFIRM studies. ENDORSE is an 8-year extension of DEFINE/CONFIRM. DESIGN/METHODS: Patients randomized to DMF 240 mg twice (BID) or three times daily (TID) in DEFINE/CONFIRM continued on the same dosage in ENDORSE. Patients randomized to placebo (PBO; DEFINE/CONFIRM) or glatiramer acetate (GA; CONFIRM) were re-randomized 1:1 to DMF 240 mg BID or TID. Adverse events (AEs) were analyzed according to treatment received in the parent/extension study: BID/BID (n=501), TID/TID (n=501), PBO/BID (n=249), PBO/TID (n=248), GA/BID (n=118), and GA/TID (n=119). RESULTS: As of May 14, 2014, total follow-up in ENDORSE for all groups was 4,980.7 patient-years. Overall incidence of AEs was as follows: BID/BID, 91[percnt]; TID/TID, 92[percnt]; PBO/BID, 95[percnt]; PBO/TID, 93[percnt]; GA/BID, 88[percnt]; and GA/TID, 85[percnt]. Incidence of serious AEs was: BID/BID, 22[percnt]; TID/TID, 25[percnt]; PBO/BID, 24[percnt]; PBO/TID, 16[percnt]; GA/BID, 16[percnt]; and GA/TID, 19[percnt]. Incidence of AEs leading to discontinuation was 6-7[percnt] and 14-26[percnt] in patients continuing and new to DMF, respectively. Incidence of serious infections was ≤4[percnt] in all groups, with no confirmed opportunistic infections. There were no new findings in hematologic outcomes compared with DEFINE/CONFIRM. Hepatic AEs occurred in ≤3[percnt] of patients in any group; there was no evidence of increased risk of renal or urinary events. There were 27 malignancies in 26 patients (18 continuing treatment and eight new to DMF). There were five deaths, none of which was considered related to study drug. CONCLUSIONS: Sustained treatment with DMF continues to demonstrate an acceptable safety profile with no new or worsening safety signals in patients with RRMS. Study Supported by: Biogen Idec Disclosure: Dr. Pozzilli has received personal compensation for activities with Actelion, Biogen Idec, Genzyme, Merck Serono, Novartis, and Teva Neuroscience as a consultant. Dr. Phillips has received personal compensation for activities with Acorda Therapeutics, Biogen Idec, Genzyme, Merck Serono, and Sanofi-Aventis Pharmaceuticals, Inc. as a consultant. Dr. Fox has received personal compensation for activities with Biogen Idec, GlaxoSmithKline, Inc., Novartis, Questcor, Teva, and Xenoport. Dr. Fox has received research support from Novartis. Dr. Selmaj has received personal compensation for activities with Genzyme Corporation, Novartis, Ono Pharmaceutical, Roche Diagnostics Corporation, Synthon, Teva Neuroscience, and Biogen Idec. as a consultant and/or speaker. Dr. Zhang has received personal compensation for activities with Biogen Idec as an employee. Dr. Novas has received personal compensation for activities with Biogen Idec as an employee. Dr. Sweetser holds stock and/or stock options in Biogen Idec. Dr. Gold has received personal compensation for activities with Bayer HealthCare, Biogen Idec, Merck Serono, Novartis, and Teva Neuroscience.