Contributions
Abstract: P661
Type: Poster
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Background: Delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF) demonstrated strong efficacy and a favourable benefit-risk in patients (pts) with relapsing-remitting multiple sclerosis (RRMS) in the Phase 3 DEFINE/CONFRIM studies, and the associated ongoing extension study, ENDORSE (NCT00835770).
Objectives: Report 8-year (yr) clinical efficacy outcomes in newly diagnosed RRMS pts treated with DMF.
Methods: Pts randomized in DEFINE/CONFIRM to DMF 240 mg twice (BID) or three times daily (TID) continued on the same dosage in ENDORSE. Pts randomized to placebo (PBO) or glatiramer acetate (CONFIRM only) were re-randomized 1:1 to DMF BID or TID. In March 2014, all pts were switched to DMF BID with regulatory approval. DMF BID results are reported. “Newly diagnosed” pts were defined as pts diagnosed with MS ≤1 yr prior to parent study entry and either treatment-naïve or previously treated with corticosteroids alone. As of October 2016, the median total follow-up was ~ 8 yrs: pts initially randomized to DMF BID in DEFINE/CONFIRM who continued on DMF BID in ENDORSE received ~ 8 yrs continuous DMF treatment (DMF/DMF); pts initially randomized to PBO who switched to DMF BID in ENDORSE received 2 yrs PBO followed by ~6 yrs DMF (PBO/DMF).
Results: At ~8 yrs (ENDORSE~ 6 yrs), 55% (79/144) DMF/DMF and 48% (41/85) PBO/DMF newly diagnosed pts remained on treatment. Over ~8 yrs, annualized relapse rate (ARR, [95% confidence interval, CI]) was 0.14 (0.10, 0.18) in DMF/DMF and 0.16 (0.11, 0.23) in PBO/DMF pts; rate ratio (95% CI) for DMF/DMF vs PBO/DMF was 0.86 (0.54, 1.37; P=0.5301). In PBO/DMF, ARR (95% CI) was 0.25 (0.18, 0.36) from Yrs 0-2 (DEFINE/CONFIRM) and 0.09 (0.06, 0.14) from Yrs 3-8 (ENDORSE); rate ratio (95% CI) for Yrs 3-8 vs 0-2 was 0.37 (0.25, 0.56; P< 0.0001). At baseline, mean (SD) expanded disability status scale (EDSS) score was 2.07 (1.16) for DMF/DMF and 2.20 (1.04) for PBO/DMF. The number of pts with EDSS≤3.5 was 129/139 (93%) and 65/72 (90%) at Yr 2, and 56/61 (92%) and 29/31 (94%) at Yr 8, for DMF/DMF and PBO/DMF, respectively. Over ~8 yrs, 52.1% DMF/DMF and 48.2% PBO/DMF pts remained free from relapses and 24-week confirmed disability progression.
Conclusions: Over ~8 yrs, ARR remained low in newly diagnosed DMF/DMF and PBO/DMF pts. ARR was significantly reduced in PBO/DMF pts after switching to DMF. The proportion of pts with EDSS≤3.5 remained stable in both treatment groups.
Supported by: Biogen
Disclosure: Gold R: Honoraria from Bayer HealthCare, Biogen, Merck Serono, Novartis, and Teva Neuroscience; Compensation from Sage for serving as editor of Therapeutic Advances in Neurological Disorders; Research support from Bayer HealthCare, Biogen, Merck Serono, Novartis, and Teva Neuroscience
Giovannoni G: 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
Phillips JT: Served as a consultant for Acorda, Biogen, Genentech, Genzyme, Merck Serono, Roche, and Sanofi.
Fox RJ: Served as a consultant for Biogen, MedDay, Novartis, Questcor, Teva, and Xenoport; served on advisory committees for Biogen and Novartis; Research grant funding from Novartis
Yang L: Employee of and holds stock/stock options in Biogen
Taylor C: Employee of and holds stock/stock options in Biogen
Abstract: P661
Type: Poster
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Background: Delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF) demonstrated strong efficacy and a favourable benefit-risk in patients (pts) with relapsing-remitting multiple sclerosis (RRMS) in the Phase 3 DEFINE/CONFRIM studies, and the associated ongoing extension study, ENDORSE (NCT00835770).
Objectives: Report 8-year (yr) clinical efficacy outcomes in newly diagnosed RRMS pts treated with DMF.
Methods: Pts randomized in DEFINE/CONFIRM to DMF 240 mg twice (BID) or three times daily (TID) continued on the same dosage in ENDORSE. Pts randomized to placebo (PBO) or glatiramer acetate (CONFIRM only) were re-randomized 1:1 to DMF BID or TID. In March 2014, all pts were switched to DMF BID with regulatory approval. DMF BID results are reported. “Newly diagnosed” pts were defined as pts diagnosed with MS ≤1 yr prior to parent study entry and either treatment-naïve or previously treated with corticosteroids alone. As of October 2016, the median total follow-up was ~ 8 yrs: pts initially randomized to DMF BID in DEFINE/CONFIRM who continued on DMF BID in ENDORSE received ~ 8 yrs continuous DMF treatment (DMF/DMF); pts initially randomized to PBO who switched to DMF BID in ENDORSE received 2 yrs PBO followed by ~6 yrs DMF (PBO/DMF).
Results: At ~8 yrs (ENDORSE~ 6 yrs), 55% (79/144) DMF/DMF and 48% (41/85) PBO/DMF newly diagnosed pts remained on treatment. Over ~8 yrs, annualized relapse rate (ARR, [95% confidence interval, CI]) was 0.14 (0.10, 0.18) in DMF/DMF and 0.16 (0.11, 0.23) in PBO/DMF pts; rate ratio (95% CI) for DMF/DMF vs PBO/DMF was 0.86 (0.54, 1.37; P=0.5301). In PBO/DMF, ARR (95% CI) was 0.25 (0.18, 0.36) from Yrs 0-2 (DEFINE/CONFIRM) and 0.09 (0.06, 0.14) from Yrs 3-8 (ENDORSE); rate ratio (95% CI) for Yrs 3-8 vs 0-2 was 0.37 (0.25, 0.56; P< 0.0001). At baseline, mean (SD) expanded disability status scale (EDSS) score was 2.07 (1.16) for DMF/DMF and 2.20 (1.04) for PBO/DMF. The number of pts with EDSS≤3.5 was 129/139 (93%) and 65/72 (90%) at Yr 2, and 56/61 (92%) and 29/31 (94%) at Yr 8, for DMF/DMF and PBO/DMF, respectively. Over ~8 yrs, 52.1% DMF/DMF and 48.2% PBO/DMF pts remained free from relapses and 24-week confirmed disability progression.
Conclusions: Over ~8 yrs, ARR remained low in newly diagnosed DMF/DMF and PBO/DMF pts. ARR was significantly reduced in PBO/DMF pts after switching to DMF. The proportion of pts with EDSS≤3.5 remained stable in both treatment groups.
Supported by: Biogen
Disclosure: Gold R: Honoraria from Bayer HealthCare, Biogen, Merck Serono, Novartis, and Teva Neuroscience; Compensation from Sage for serving as editor of Therapeutic Advances in Neurological Disorders; Research support from Bayer HealthCare, Biogen, Merck Serono, Novartis, and Teva Neuroscience
Giovannoni G: 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
Phillips JT: Served as a consultant for Acorda, Biogen, Genentech, Genzyme, Merck Serono, Roche, and Sanofi.
Fox RJ: Served as a consultant for Biogen, MedDay, Novartis, Questcor, Teva, and Xenoport; served on advisory committees for Biogen and Novartis; Research grant funding from Novartis
Yang L: Employee of and holds stock/stock options in Biogen
Taylor C: Employee of and holds stock/stock options in Biogen