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Long-term effects of delayed-release dimethyl fumarate in multiple sclerosis: Interim analysis of ENDORSE, a randomized extension study

R. Gold, DL. Arnold, A. Bar-Or, M. Hutchinson, L. Kappos, E. Havrdova, DG. MacManus, TA. Yousry, C. Pozzilli, K. Selmaj, MT. Sweetser, R. Zhang, M. Yang, J. Potts, M. Novas, DH. Miller, NC. Kurukulasuriya, RJ. Fox, TJ. Phillips,

. 2017 ; 23 (2) : 253-265. [pub] 20160711

Language English Country Great Britain

Document type Journal Article, Randomized Controlled Trial

Persistent link   https://www.medvik.cz/link/bmc18011209

BACKGROUND: Delayed-release dimethyl fumarate (DMF) demonstrated strong efficacy and a favorable benefit-risk profile for patients with relapsing-remitting multiple sclerosis (RRMS) in phase 3 DEFINE/CONFIRM studies. ENDORSE is an ongoing long-term extension of DEFINE/CONFIRM. OBJECTIVE: We report efficacy and safety results of a 5-year interim analysis of ENDORSE (2 years DEFINE/CONFIRM; minimum 3 years ENDORSE). METHODS: In ENDORSE, patients randomized to DMF 240 mg twice (BID) or thrice daily (TID) in DEFINE/CONFIRM continued this dosage, and those initially randomized to placebo (PBO) or glatiramer acetate (GA) were re-randomized to DMF 240 mg BID or TID. RESULTS: For patients continuing DMF BID (BID/BID), annualized relapse rates were 0.202, 0.163, 0.139, 0.143, and 0.138 (years 1-5, respectively) and 63%, 73%, and 88% were free of new or enlarging T2 hyperintense lesions, new T1 hypointense lesions, and gadolinium-enhanced lesions, respectively, at year 5. Adverse events (AEs; serious adverse events (SAEs)) were reported in 91% (22%; BID/BID), 95% (24%; PBO/BID), and 88% (16%; GA/BID) of the patients. One case of progressive multifocal leukoencephalopathy was reported in the setting of severe, prolonged lymphopenia. CONCLUSION: Treatment with DMF was associated with continuously low clinical and magnetic resonance imaging (MRI) disease activity in patients with RRMS. These interim data demonstrate a sustained treatment benefit and an acceptable safety profile with DMF.

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$a BACKGROUND: Delayed-release dimethyl fumarate (DMF) demonstrated strong efficacy and a favorable benefit-risk profile for patients with relapsing-remitting multiple sclerosis (RRMS) in phase 3 DEFINE/CONFIRM studies. ENDORSE is an ongoing long-term extension of DEFINE/CONFIRM. OBJECTIVE: We report efficacy and safety results of a 5-year interim analysis of ENDORSE (2 years DEFINE/CONFIRM; minimum 3 years ENDORSE). METHODS: In ENDORSE, patients randomized to DMF 240 mg twice (BID) or thrice daily (TID) in DEFINE/CONFIRM continued this dosage, and those initially randomized to placebo (PBO) or glatiramer acetate (GA) were re-randomized to DMF 240 mg BID or TID. RESULTS: For patients continuing DMF BID (BID/BID), annualized relapse rates were 0.202, 0.163, 0.139, 0.143, and 0.138 (years 1-5, respectively) and 63%, 73%, and 88% were free of new or enlarging T2 hyperintense lesions, new T1 hypointense lesions, and gadolinium-enhanced lesions, respectively, at year 5. Adverse events (AEs; serious adverse events (SAEs)) were reported in 91% (22%; BID/BID), 95% (24%; PBO/BID), and 88% (16%; GA/BID) of the patients. One case of progressive multifocal leukoencephalopathy was reported in the setting of severe, prolonged lymphopenia. CONCLUSION: Treatment with DMF was associated with continuously low clinical and magnetic resonance imaging (MRI) disease activity in patients with RRMS. These interim data demonstrate a sustained treatment benefit and an acceptable safety profile with DMF.
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$a Arnold, Douglas L $u NeuroRx Research, Montreal, QC, Canada/Montreal Neurological Institute, McGill University, Montreal, QC, Canada.
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$a Hutchinson, Michael $u St. Vincent's University Hospital, Dublin, Ireland.
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$a Kappos, Ludwig $u Department of Neurology, University Hospital of Basel, Basel, Switzerland.
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$a Havrdova, Eva $u Department of Neurology, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.
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$a MacManus, David G $u NMR Research Unit, Queen Square Multiple Sclerosis Centre, University College London (UCL) Institute of Neurology, London, UK.
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$a Yousry, Tarek A $u NMR Research Unit, Queen Square Multiple Sclerosis Centre, University College London (UCL) Institute of Neurology, London, UK.
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$a Pozzilli, Carlo $u Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy.
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$a Selmaj, Krysztof $u Medical University of Lodz, Lodz, Poland.
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$a Sweetser, Marianne T $u Biogen, Cambridge, MA, USA.
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$a Potts, James $u Biogen, Cambridge, MA, USA.
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$a Novas, Mark $u Biogen, Cambridge, MA, USA.
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$a Miller, David H $u NMR Research Unit, Queen Square Multiple Sclerosis Centre, University College London (UCL) Institute of Neurology, London, UK.
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$a Kurukulasuriya, Nuwan C $u Biogen, Cambridge, MA, USA.
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$a Fox, Robert J $u Cleveland Clinic, Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland, OH, USA.
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