Contributions
Abstract: P920
Type: Poster Sessions
Abstract Category: Therapy - Long-term treatment monitoring
Introduction: Long-term follow-up data are useful to characterise the efficacy and safety of disease-modifying therapies when initiating treatment in newly diagnosed patients with relapsing-remitting multiple sclerosis (RRMS). Delayed-release dimethyl fumarate (DMF) demonstrated strong efficacy and a favourable benefit-risk profile in RRMS patients in Phase 3 studies (DEFINE/CONFIRM), which is sustained in the ongoing extension study, ENDORSE (NCT00835770).
Objectives: To evaluate efficacy in newly diagnosed patients with RRMS treated with DMF for ~9 years.
Methods: “Newly diagnosed” patients were diagnosed with MS ≤1 year before DEFINE and CONFIRM study entry and were either treatment-naïve or previously treated with corticosteroids alone. An integrated analysis of newly diagnosed patients who continued after 2 years onto the ENDORSE study assessed annualised relapse rate (ARR) and expanded disability status scale (EDSS) score. Results are reported for patients treated with DMF 240 mg BID: placebo (PBO)/DMF (PBO for Years 0-2 /DMF for Years 3-9) or continuous (DMF/DMF) treatment.
Results: As of September 2017, all newly diagnosed patients have total follow-up (including DEFINE/CONFIRM) ~9 years (median 8.6 years, range 2.1-10.8, 1 year=48 weeks); among whom 50% (72/144) DMF/DMF and 45% (38/85) PBO/DMF remained on treatment. The primary reason for discontinuation was 'other' for DMF/DMF (17/61: 'want/become pregnant´ n=7; ´moving to a different city/country´ n=3; ´site closure´ n=2; other reasons n=5) and 'adverse event' for PBO/DMF (14/43). 7/61 and 3/43 patients in the DMF/DMF and PBO/DMF groups, respectively, discontinued the study specifically due to MS. Over 9 years, adjusted ARR (95% CI) was 0.14 (0.10-0.18) for DMF/DMF and 0.15 (0.10-0.23) for PBO/DMF. For PBO/DMF, adjusted ARR (95% CI) was 0.25 (0.18-0.37) for Years 0-2 (PBO) and 0.09 (0.06-0.14) for Years 3-9 (DMF); the rate ratio (95% CI) was 0.36 (0.23-0.55; P< 0.0001), representing a 64% decrease in ARR after initiating DMF. The observed proportion of patients with EDSS ≤3.5 was 129/139 (93%) and 65/72 (90%) at Year 2, and 50/54 (93%) and 26/28 (93%) at Year 9 for DMF/DMF and PBO/DMF, respectively.
Conclusions: The majority of patients remaining on study maintained walking abilities (EDSS ≤3.5) over 9 years. ARR decreased significantly in PBO/DMF patients after initiating DMF, and remained low for newly diagnosed patients after 9 years.
Supported by: Biogen.
Disclosure: Gold: 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: Honoraria from Abbvie, Bayer HealthCare, Biogen, Canbex, FivePrime, Genzyme, GlaxoSmithKline, GW Pharma, 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: Advisory board, speaking or consulting fees from Acorda, Alexion, Biogen, and TG Therapeutics.Bar-Or: Speaker fees, consulting fees and/or grant support from Atara Biotherapeutics, Biogen, Celgene/Receptos, Genentech/Roche, GlaxoSmithKline, Medimmune, Merck/EMD Serono, Novartis, Sanofi-Genzyme.Fox: Consultant fees from Biogen, MedDay, Novartis, Questcor, Teva, and Xenoport; advisory committees for Biogen and Novartis; Research grant funding from Novartis.Chen: Employee of and holds stock/stock options in Biogen.Taylor: Employee of and holds stock/stock options in Biogen.
Abstract: P920
Type: Poster Sessions
Abstract Category: Therapy - Long-term treatment monitoring
Introduction: Long-term follow-up data are useful to characterise the efficacy and safety of disease-modifying therapies when initiating treatment in newly diagnosed patients with relapsing-remitting multiple sclerosis (RRMS). Delayed-release dimethyl fumarate (DMF) demonstrated strong efficacy and a favourable benefit-risk profile in RRMS patients in Phase 3 studies (DEFINE/CONFIRM), which is sustained in the ongoing extension study, ENDORSE (NCT00835770).
Objectives: To evaluate efficacy in newly diagnosed patients with RRMS treated with DMF for ~9 years.
Methods: “Newly diagnosed” patients were diagnosed with MS ≤1 year before DEFINE and CONFIRM study entry and were either treatment-naïve or previously treated with corticosteroids alone. An integrated analysis of newly diagnosed patients who continued after 2 years onto the ENDORSE study assessed annualised relapse rate (ARR) and expanded disability status scale (EDSS) score. Results are reported for patients treated with DMF 240 mg BID: placebo (PBO)/DMF (PBO for Years 0-2 /DMF for Years 3-9) or continuous (DMF/DMF) treatment.
Results: As of September 2017, all newly diagnosed patients have total follow-up (including DEFINE/CONFIRM) ~9 years (median 8.6 years, range 2.1-10.8, 1 year=48 weeks); among whom 50% (72/144) DMF/DMF and 45% (38/85) PBO/DMF remained on treatment. The primary reason for discontinuation was 'other' for DMF/DMF (17/61: 'want/become pregnant´ n=7; ´moving to a different city/country´ n=3; ´site closure´ n=2; other reasons n=5) and 'adverse event' for PBO/DMF (14/43). 7/61 and 3/43 patients in the DMF/DMF and PBO/DMF groups, respectively, discontinued the study specifically due to MS. Over 9 years, adjusted ARR (95% CI) was 0.14 (0.10-0.18) for DMF/DMF and 0.15 (0.10-0.23) for PBO/DMF. For PBO/DMF, adjusted ARR (95% CI) was 0.25 (0.18-0.37) for Years 0-2 (PBO) and 0.09 (0.06-0.14) for Years 3-9 (DMF); the rate ratio (95% CI) was 0.36 (0.23-0.55; P< 0.0001), representing a 64% decrease in ARR after initiating DMF. The observed proportion of patients with EDSS ≤3.5 was 129/139 (93%) and 65/72 (90%) at Year 2, and 50/54 (93%) and 26/28 (93%) at Year 9 for DMF/DMF and PBO/DMF, respectively.
Conclusions: The majority of patients remaining on study maintained walking abilities (EDSS ≤3.5) over 9 years. ARR decreased significantly in PBO/DMF patients after initiating DMF, and remained low for newly diagnosed patients after 9 years.
Supported by: Biogen.
Disclosure: Gold: 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: Honoraria from Abbvie, Bayer HealthCare, Biogen, Canbex, FivePrime, Genzyme, GlaxoSmithKline, GW Pharma, 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: Advisory board, speaking or consulting fees from Acorda, Alexion, Biogen, and TG Therapeutics.Bar-Or: Speaker fees, consulting fees and/or grant support from Atara Biotherapeutics, Biogen, Celgene/Receptos, Genentech/Roche, GlaxoSmithKline, Medimmune, Merck/EMD Serono, Novartis, Sanofi-Genzyme.Fox: Consultant fees from Biogen, MedDay, Novartis, Questcor, Teva, and Xenoport; advisory committees for Biogen and Novartis; Research grant funding from Novartis.Chen: Employee of and holds stock/stock options in Biogen.Taylor: Employee of and holds stock/stock options in Biogen.