PMID- 37061656 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230522 IS - 2193-8253 (Print) IS - 2193-6536 (Electronic) IS - 2193-6536 (Linking) VI - 12 IP - 3 DP - 2023 Jun TI - Efficacy of Dimethyl Fumarate in Young Adults with Relapsing-Remitting Multiple Sclerosis: Analysis of the DEFINE, CONFIRM, and ENDORSE Studies. PG - 883-897 LID - 10.1007/s40120-023-00475-8 [doi] AB - INTRODUCTION: Dimethyl fumarate (DMF) showed favorable benefit-risk in patients with relapsing-remitting multiple sclerosis (MS) in phase 3 DEFINE and CONFIRM trials and in the ENDORSE extension study. Disease activity can differ in younger patients with MS compared with the overall population. METHODS: Randomized patients received DMF 240 mg twice daily or placebo (PBO; years 0-2 DEFINE/CONFIRM), then DMF (years 3-10; continuous DMF/DMF or PBO/DMF; ENDORSE); maximum follow-up (combined studies) was 13 years. This integrated post hoc analysis evaluated safety and efficacy of DMF in a subgroup of young adults aged 18-29 years. RESULTS: Of 1736 patients enrolled in ENDORSE, 125 were young adults, 86 treated continuously with DMF (DMF/DMF) and 39 received delayed DMF (PBO/DMF) in DEFINE/CONFIRM. Most (n = 116 [93%]) young adults completed DMF treatment in DEFINE/CONFIRM. Median (range) follow-up time in ENDORSE was 6.5 (2.0-10.0) years. Young adults entering ENDORSE who had been treated with DMF in DEFINE/CONFIRM had a model-based Annualized Relapse Rate (ARR; 95% CI) of 0.24 (0.16-0.35) vs. 0.56 (0.35-0.88) in PBO patients. ARR remained low in ENDORSE: 0.07 (0.01-0.47) at years 9-10 (DMF/DMF group). At year 10 of ENDORSE, EDSS scores were low in young adults: DMF/DMF, 1.9 (1.4); PBO/DMF, 2.4 (1.6). At ~ 7 years, the proportion of young adults with no confirmed disability progresion was 81% for DMF/DMF and 72% for PBO/DMF. Patient-reported outcomes (PROs) (SF-36 and EQ-5D) generally remained stable during ENDORSE. The most common adverse events (AEs) in young adults during ENDORSE were MS relapse (n = 53 [42%]). Most AEs were mild (n = 20 [23.3%], n = 7 [17.9%]) to moderate (n = 45 [52.3%], n = 23 [59.0%]) in the DMF/DMF and PBO/DMF groups, respectively. The most common serious AE (SAE) was MS relapse (n = 19 [15%]). CONCLUSION: The data support a favorable benefit-risk profile of DMF in young adults, as evidenced by well-characterized safety, sustained efficacy, and stable PROs. CLINICAL TRIAL INFORMATION: Clinical trials.gov, DEFINE (NCT00420212), CONFIRM (NCT00451451), and ENDORSE (NCT00835770). CI - (c) 2023. The Author(s). FAU - Amezcua, Lilyana AU - Amezcua L AUID- ORCID: 0000-0003-1542-7819 AD - Multiple Sclerosis Comprehensive Care Center, University of Southern California, Los Angeles, CA, USA. AD - Department of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. FAU - Mao-Draayer, Yang AU - Mao-Draayer Y AUID- ORCID: 0000-0001-6248-3480 AD - Autoimmunity Center of Excellence, Department of Neurology, University of Michigan Medical School, Ann Arbor, MI, USA. AD - Graduate Program in Immunology, Program in Biomedical Sciences, University of Michigan Medical School, Ann Arbor, MI, USA. FAU - Vargas, Wendy S AU - Vargas WS AD - Columbia Multiple Sclerosis Center, Department of Neurology, Columbia University Irving Medical Center, New York, NY, USA. FAU - Farber, Rebecca AU - Farber R AD - Columbia Multiple Sclerosis Center, Department of Neurology, Columbia University Irving Medical Center, New York, NY, USA. FAU - Schaefer, Sara AU - Schaefer S AD - Multiple Sclerosis Comprehensive Care Center, UC-Health Neurology Clinic, Fort Collins, CO, USA. FAU - Branco, Filipe AU - Branco F AD - Biogen, Cambridge, MA, USA. FAU - England, Sarah M AU - England SM AD - Biogen, Cambridge, MA, USA. FAU - Belviso, Nicholas AU - Belviso N AD - Biogen, Cambridge, MA, USA. FAU - Lewin, James B AU - Lewin JB AUID- ORCID: 0000-0002-2352-9113 AD - Biogen, Cambridge, MA, USA. FAU - Mendoza, Jason P AU - Mendoza JP AUID- ORCID: 0000-0003-2526-5542 AD - Biogen, Cambridge, MA, USA. FAU - Shankar, Sai L AU - Shankar SL AUID- ORCID: 0000-0003-3249-8360 AD - Biogen, Cambridge, MA, USA. sai.shankar@biogen.com. AD - , 133 Boston Post Road, Weston, MA, 02493, USA. sai.shankar@biogen.com. CN - ENDORSE Study Investigators LA - eng SI - ClinicalTrials.gov/NCT00835770 SI - ClinicalTrials.gov/NCT00451451 PT - Journal Article DEP - 20230415 PL - New Zealand TA - Neurol Ther JT - Neurology and therapy JID - 101637818 PMC - PMC10195942 OTO - NOTNLM OT - DMT OT - Dimethyl fumarate OT - Efficacy OT - Multiple sclerosis OT - Safety OT - Young adults COIS- Lilyana Amezcua: advisory/consulting fees from EMD Serono, Genzyme, and Novartis; research support from Biogen and MedDay. Yang Mao-Draayer: consulting fees from Biogen, Celgene, EMD Serono, Genzyme, Novartis, Janssen, Horizon, and Roche-Genentech; contracted research for NIH NINDS R01-NS080821, NIAID Autoimmune Center of Excellence UM1-AI110557, Biogen, Chugai, Novartis, and Sanofi-Genzyme; speaker bureaus for Biogen and Teva. Wendy S. Vargas: advisory/consulting fees from Alexion, Biogen, Genentech, and Octapharma; research support from Teva. Rebecca Farber: Consulting fees for Alexion and Genentech; research grants from Novartis and Biogen; research support from NIH, grant number 2U19AI128949-06. Sara Schaefer: Consulting/advisory fees from Novartis, Biogen, and Genzyme; speaking fees from Biogen. Filipe Branco, Sarah M. England, Nicholas Belviso, James B. Lewin, Jason P. Mendoza, and Sai L. Shankar are employees and stockholders of Biogen. EDAT- 2023/04/16 06:00 MHDA- 2023/04/16 06:01 PMCR- 2023/04/15 CRDT- 2023/04/15 23:21 PHST- 2023/02/07 00:00 [received] PHST- 2023/03/27 00:00 [accepted] PHST- 2023/04/16 06:01 [medline] PHST- 2023/04/16 06:00 [pubmed] PHST- 2023/04/15 23:21 [entrez] PHST- 2023/04/15 00:00 [pmc-release] AID - 10.1007/s40120-023-00475-8 [pii] AID - 475 [pii] AID - 10.1007/s40120-023-00475-8 [doi] PST - ppublish SO - Neurol Ther. 2023 Jun;12(3):883-897. doi: 10.1007/s40120-023-00475-8. Epub 2023 Apr 15.