Overall safety and efficacy through 10 years of treatment with delayed-release dimethyl fumarate in patients with relapsing-remitting multiple sclerosis
ECTRIMS Online Library. Gold R. 09/13/19; 278597; P1397
Ralf Gold
Ralf Gold
Contributions
Abstract

Abstract: P1397

Type: Poster Sessions

Abstract Category: Therapy - Long-term treatment monitoring

R. Gold1, G. Giovannoni2, J.T. Phillips3, A. Bar-Or4,5, R.J. Fox6, C. Chen7, C. Miller7, F. Branco8

1Dept. of Neurology, St. Josef-Hospital, Ruhr University Bochum, Bochum, Germany, 2Blizzard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom, 3Multiple Sclerosis Program, Baylor Institute for Immunology Research, Dallas, TX, 4Department of Neurology and Center for Neuroinflammation and Experimental Therapeutics, Perelman School of Medicine, 5Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 6Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, Cleveland, OH, 7Biogen, Cambridge, MA, United States, 8Biogen, Baar, Switzerland

Introduction: Delayed-release dimethyl fumarate (DMF) demonstrated a favourable benefit-risk profile in patients with relapsing-remitting multiple sclerosis (RRMS) in the Phase 3 DEFINE/CONFIRM studies, and the ongoing extension, ENDORSE (NCT00835770).
Objectives: To report clinical efficacy outcomes and overall safety results in a subpopulation of patients treated with DMF for at least 10 years (yrs) in ENDORSE.
Methods: Patients randomised in DEFINE/CONFIRM to DMF 240 mg twice (BID) or thrice-daily (TID) continued on the same dosage in ENDORSE. Patients randomised to placebo (PBO) or glatiramer acetate (CONFIRM only) were re-randomised 1:1 to DMF BID or TID. Outcomes for patients treated continuously with DMF 240 mg BID are reported: measures of MS disease activity (relapse and confirmed progression of disability [CDP]), serious adverse events (SAEs), and patient-reported outcomes (PROs) (36-item short form health survey [SF-36] and 5-dimension QoL [EQ-5D]).
Results:
Of 618 patients with follow up for at least 10 yrs, 192 were continuously treated BID. Mean (SD) age was 41.6 (8.7) yrs; 68% were female. Fifty-one percent (98/192) of patients remained relapse-free; 22% (43/192) had 1 relapse and 26% (51/196) experienced ≥2 relapses over ≥10 yr treatment period. The median time to first relapse was 518 weeks. At baseline, mean (SD) expanded disability status scale (EDSS) score was 2.24 (1.18). The number of patients with EDSS ≤3.5 was 164/184 (89%) at Yr 2, 148/184 (80%) at Yr 8, and 146/184 (79%) at Yr 10. Over 10 yrs, 64% (122/191) of patients had no CDP. Overall, 77 (40%) patients experienced SAEs; most were MS relapse (44%, 34/77) or infections (16%; 12/77). Over 10 yrs, there was no increased incidence of serious infection, Yr >0-1, 2% (3/192); Yr >1-2, (0/192); Yr >2-3, (0/192); Yr >3-4, < 1% (1/192); Yr >4-5, < 1% (1/192); Yr >5-6, 1% (2/192); Yr >6-7, (0/192); Yr >7-8, 1% (2/192); Yr >8-9, 1% (2/192); Yr >9-10, < 1% (1/192); >10 yrs, < 1% (1/192). Patients generally remained stable on SF-36 and EQ-5D from baseline to Yr 10.
Conclusions: Sustained treatment with DMF was associated with low incidence of relapses. The proportion of patients with EDSS ≤3.5 remained stable over time and number of patients with CDP over 10 yrs remained low. There was no increased incidence of serious infections over time, and PROs remained stable. These results support the safety and efficacy of DMF as a long-term treatment option for patients with RRMS.
Disclosure: Ralf Gold: honoraria/research support from Bayer HealthCare, Biogen, Merck Serono, Novartis, and Teva Neuroscience; compensation from Sage for serving as editor of Therapeutic Advances in Neurological Disorders
Gavin Giovannoni: Honoraria from Abbvie, Almirall, Atara Bio, Bayer HealthCare, Biogen, Canbex, FivePrime, Genzyme, GlaxoSmithKline, GW Pharma, MedDay, Merck Serono, Novartis, Protein Discovery Laboratories, Roche, Synthon, Teva Neuroscience, UCB, and Vertex; Compensation from Elsevier as co-chief editor of MS and Related Disorders; Research grant support from Biogen, Ironwood, Merck Serono, Merz, and Novartis
J. Theodore Phillips: Served as a consultant for Acorda, Biogen, Genentech, Genzyme, Merck Serono, Roche, and Sanofi.
Amit Bar-Or: speaker/consulting fees/grant support from Atara Biotherapeutics, Biogen, Celgene/Receptos, Genentech/Roche, GlaxoSmithKline, MedImmune, Merck/EMD Serono, Novartis, and Sanofi-Genzyme;
Robert J. Fox: consulting fees from Biogen, MedDay, Novartis, Questcor, Teva, and XenoPort; advisory committees for Biogen and Novartis; research grant funding from Novartis;
Chongshu Chen, Catherine Miller, Fillipe Branco: employees of and hold stock/stock options in Biogen
Supported by: Writing and editorial support for the preparation of this abstract was provided by Excel Scientific Solutions (Southport, CT, USA): funding was provided by Biogen.

Abstract: P1397

Type: Poster Sessions

Abstract Category: Therapy - Long-term treatment monitoring

R. Gold1, G. Giovannoni2, J.T. Phillips3, A. Bar-Or4,5, R.J. Fox6, C. Chen7, C. Miller7, F. Branco8

1Dept. of Neurology, St. Josef-Hospital, Ruhr University Bochum, Bochum, Germany, 2Blizzard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom, 3Multiple Sclerosis Program, Baylor Institute for Immunology Research, Dallas, TX, 4Department of Neurology and Center for Neuroinflammation and Experimental Therapeutics, Perelman School of Medicine, 5Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 6Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, Cleveland, OH, 7Biogen, Cambridge, MA, United States, 8Biogen, Baar, Switzerland

Introduction: Delayed-release dimethyl fumarate (DMF) demonstrated a favourable benefit-risk profile in patients with relapsing-remitting multiple sclerosis (RRMS) in the Phase 3 DEFINE/CONFIRM studies, and the ongoing extension, ENDORSE (NCT00835770).
Objectives:
To report clinical efficacy outcomes and overall safety results in a subpopulation of patients treated with DMF for at least 10 years (yrs) in ENDORSE.
Methods: Patients randomised in DEFINE/CONFIRM to DMF 240 mg twice (BID) or thrice-daily (TID) continued on the same dosage in ENDORSE. Patients randomised to placebo (PBO) or glatiramer acetate (CONFIRM only) were re-randomised 1:1 to DMF BID or TID. Outcomes for patients treated continuously with DMF 240 mg BID are reported: measures of MS disease activity (relapse and confirmed progression of disability [CDP]), serious adverse events (SAEs), and patient-reported outcomes (PROs) (36-item short form health survey [SF-36] and 5-dimension QoL [EQ-5D]).
Results:
Of 618 patients with follow up for at least 10 yrs, 192 were continuously treated BID. Mean (SD) age was 41.6 (8.7) yrs; 68% were female. Fifty-one percent (98/192) of patients remained relapse-free; 22% (43/192) had 1 relapse and 26% (51/196) experienced ≥2 relapses over ≥10 yr treatment period. The median time to first relapse was 518 weeks. At baseline, mean (SD) expanded disability status scale (EDSS) score was 2.24 (1.18). The number of patients with EDSS ≤3.5 was 164/184 (89%) at Yr 2, 148/184 (80%) at Yr 8, and 146/184 (79%) at Yr 10. Over 10 yrs, 64% (122/191) of patients had no CDP. Overall, 77 (40%) patients experienced SAEs; most were MS relapse (44%, 34/77) or infections (16%; 12/77). Over 10 yrs, there was no increased incidence of serious infection, Yr >0-1, 2% (3/192); Yr >1-2, (0/192); Yr >2-3, (0/192); Yr >3-4, < 1% (1/192); Yr >4-5, < 1% (1/192); Yr >5-6, 1% (2/192); Yr >6-7, (0/192); Yr >7-8, 1% (2/192); Yr >8-9, 1% (2/192); Yr >9-10, < 1% (1/192); >10 yrs, < 1% (1/192). Patients generally remained stable on SF-36 and EQ-5D from baseline to Yr 10.
Conclusions: Sustained treatment with DMF was associated with low incidence of relapses. The proportion of patients with EDSS ≤3.5 remained stable over time and number of patients with CDP over 10 yrs remained low. There was no increased incidence of serious infections over time, and PROs remained stable. These results support the safety and efficacy of DMF as a long-term treatment option for patients with RRMS.
Disclosure: Ralf Gold: honoraria/research support from Bayer HealthCare, Biogen, Merck Serono, Novartis, and Teva Neuroscience; compensation from Sage for serving as editor of Therapeutic Advances in Neurological Disorders
Gavin Giovannoni: Honoraria from Abbvie, Almirall, Atara Bio, Bayer HealthCare, Biogen, Canbex, FivePrime, Genzyme, GlaxoSmithKline, GW Pharma, MedDay, Merck Serono, Novartis, Protein Discovery Laboratories, Roche, Synthon, Teva Neuroscience, UCB, and Vertex; Compensation from Elsevier as co-chief editor of MS and Related Disorders; Research grant support from Biogen, Ironwood, Merck Serono, Merz, and Novartis
J. Theodore Phillips: Served as a consultant for Acorda, Biogen, Genentech, Genzyme, Merck Serono, Roche, and Sanofi.
Amit Bar-Or: speaker/consulting fees/grant support from Atara Biotherapeutics, Biogen, Celgene/Receptos, Genentech/Roche, GlaxoSmithKline, MedImmune, Merck/EMD Serono, Novartis, and Sanofi-Genzyme;
Robert J. Fox: consulting fees from Biogen, MedDay, Novartis, Questcor, Teva, and XenoPort; advisory committees for Biogen and Novartis; research grant funding from Novartis;
Chongshu Chen, Catherine Miller, Fillipe Branco: employees of and hold stock/stock options in Biogen
Supported by: Writing and editorial support for the preparation of this abstract was provided by Excel Scientific Solutions (Southport, CT, USA): funding was provided by Biogen.

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