Aim: Anti-CD20 monoclonal antibodies and fumarates are common multiple sclerosis (MS) diseasemodifying therapies (DMTs). Data on switching from anti-CD20s to other DMTs are limited. This retrospective, observational study of the US Komodo Health Sentinel claims database aimed to evaluate a de-escalation strategy in a real-world cohort, comparing clinical characteristics, relapses, healthcare encounters (HCEs) and healthcare costs (HCCs) between patients aged ≥18 years with stable MS who switched from anti-CD20s to fumarates (‘Switchers’) versus patients who stayed on anti-CD20s (‘Stayers’). Materials & methods: Patients withMS (diagnosed 1 January 2015–31 August 2022) were propensity score matched 5:1 (Stayers:Switchers) and followed from index to end of study; end of insurance eligibility; >45- day gap in index DMT; or DMT switch. Primary outcomes were clinical characteristics and claims-based annualized relapse rate (ARR). Rates of HCEs and HCCs were estimated. Results: Baseline characteristics were well balanced between cohorts (Stayers, n = 540; Switchers, n = 108). Mean (SD) duration of postindex follow-up was 341.4 (250.0) days for both cohorts. Mean (SD) ARR was 0.08 (0.41; Stayers) versus 0.14 (0.5; Switchers; p = 0.3). Twenty-one Stayers (3.9%) and 1 Switcher (0.9%) were hospitalized for infections, with mean stays of 9.9 and 1 day, respectively. Mean annualized all-cause HCEs were similar between cohorts; annualized inpatient infection-related HCEs were higher for Stayers versus Switchers (mean difference: -0.05; p = 0.005). Annualized all-cause HCCs were similar between cohorts; Switchers had lower annualized infection-related HCCs overall (mean difference: -$2412; p = 0.002) and in the inpatient setting (mean difference: -$2325; p = 0.002). Conclusion: After 1 year, no significant differences in ARR emerged between cohorts. Switchers experienced lower inpatient infection-related HCEs, shorter inpatient infection-related hospital stays and lower overall infection-related HCCs.

Background: Dimethyl fumarate (DMF) has a favorable benefit-risk profile treating people with multiple sclerosis and should be used in pregnant women only if the potential benefits outweigh potential risks to the fetus. Objective: Assess pregnancy outcomes in a completed international registry (TecGistry) of women with MS exposed to DMF. Methods: TecGistry included pregnant women with MS exposed to DMF, with data collected at enrollment, 6-7 months gestation, 4 weeks after estimated due date, and at postpartum weeks 4, 12, and 52. Outcomes included live births, gestational size, pregnancy loss, ectopic/molar pregnancies, birth defects, and infant/maternal death. Results: Of 397 enrolled, median (range) age was 32 years (19-43). Median (range) gestational week at enrollment was 10 (0-39) and at first DMF exposure was 1 (0-13). Median (range) duration of gestational DMF exposure was 5 weeks (0-40). Fifteen (3.8%) spontaneous abortions occurred. Of 360 (89.1%) live births, 323 were full term and 37 were premature. One neonatal death and no maternal deaths occurred. Adjudicator-confirmed EUROCAT birth defects were found in 2.2%. Conclusion: DMF exposure during pregnancy did not adversely affect pregnancy outcomes; birth defects, preterm birth, and spontaneous abortion were in line with rates from the general population.

Background: Multiple sclerosis (MS) has not been well studied in racial and ethnic minorities, as these populations are typically underrepresented in clinical trials. Black or African Americans comprise similar to 13 % of the US population, yet are represented by as little as 5 % in clinical trials. Differences in disease course and progression have been reported between races and ethnicities, so there is a need to understand the safety and efficacy of disease-modifying therapies (DMTs) in Black patients, to inform evidence-based approaches to treatment in this population. Methods: EVOLVE-MS-1 (NCT0234307) was an open-label, single-arm, phase 3 study assessing the long-term safety, tolerability, and efficacy of diroximel fumarate (DRF) over 96 weeks in adults with relapsing-remitting multiple sclerosis (RRMS). Patients were either newly initiated to DRF or rolled over from completing EVOLVE-MS-2 (NCT03093324). In this post-hoc analysis of the phase 3 EVOLVE-MS-1 study, we evaluate the safety and exploratory efficacy outcomes for DRF in Black and non-Black patient subgroups. Results: Of 1057 patients enrolled, 72 (6.8 %) were Black. In Black vs non-Black patients, mean age was 42 vs 43 years and 75 % vs 72 % were female, respectively. In both groups, median (range) duration of DRF exposure was 1.8 (0.0-2.0) years and mean Expanded Disability Status Scale (EDSS) was 2.7. The most common prior DMTs for both Black vs non-Black patients were interferons (47 % vs 37 %) and glatiramer acetate (36 % vs 24 %). DRF treatment was discontinued in 33 (46 %) Black and 224 (23 %) non-Black patients; most common reasons for discontinuation were withdrawal by patient (n = 11, 15.3 %), adverse events (AEs; n = 7, 9.7 %), and lost to follow-up (n = 7, 9.7 %) in Black patients; AEs (8.2 %) and withdrawal by patient (7.0 %) in non-Black patients. AEs were reported in 90 % Black and 89 % non-Black patients; most AEs were mild or moderate in both groups. Gastrointestinal (GI) AEs were reported in 36 % Black and 32 % non-Black patients; no Black patients discontinued due to GI AEs, vs 7 (0.7 %) non-Black patients. The most commonly reported AE was flushing (18 % Black and 28 % non-Black patients). No AEs of lymphopenia were reported in Black patients compared with 13 % of non-Black patients. Mean absolute lymphocyte count declined from baseline to week 48 by 15 % in Black patients and 29 % in non-Black patients, then plateaued and remained above the lower limit of normal (LLN; 0.91 x 10(9)/L). Adjusted annualized relapse rate (95 % confidence interval) was reduced by 78.2 % (54.6 - 89.5; p < 0.0001) in Black patients, from 12 months before to 96 weeks after DRF treatment; similar to 81.7 % (78.5 - 84.5 %; p < 0.0001) reduction in non-Black patients. Mean number of patients free from confirmed disability progression was 93.4 % by week 48, then 86.2 % vs 90.4 % by week 96 in Black vs non-Black patients, respectively. Conclusion: This study presents the first analysis of safety and efficacy of DRF in Black patients. Relapse rates remained low in Black patients on DRF, consistent with non-Black patients, and there were no new safety signals identified in the Black patient subgroup in EVOLVE-MS-1. Together, these outcomes support DRF as an effective treatment option in Black patients with RRMS.

Background: Pregnancy is a common consideration for people with multiple sclerosis (pwMS); MS onset is typically between 20 and 45 years of age, during potential child-bearing years. Pregnancy and postpartum care are a significant factor influencing disease-modifying therapy (DMT) selection for many pwMS. To date, few DMTs are considered safe to continue during pregnancy and real-world treatment patterns before, during, and after pregnancy remain uncharacterized. Evolving guidance is needed regarding how to optimize management of the pregnancy and postpartum periods considering the changing DMT landscape. This analysis in two large claims databases describes DMT utilization for the treatment of MS before, during, and after pregnancy and relapse patterns during pregnancy and postpartum. Methods: In this retrospective, observational study, the US MarketScan Commercial and Medicaid claims database was assessed for female patients aged 18-55 years with >= 1 insurance claim submitted under the diagnosis code of MS from 01 January 2016-30 April 2021 and continuous enrollment eligibility from >= 6 months prior to pregnancy date (preconception) through 6 months of follow-up following delivery (postpartum period). Comorbid conditions were examined preconception and postpartum, including anxiety and depression. Moderate/severe relapse was defined as MS-related hospitalization, or an outpatient visit and one claim within 7 days of the visit with steroids or total plasma exchange. Results: A total of 944 patients (mean [standard deviation] age, 32.4 [5.0] years) were eligible; 688 (73%) were commercially insured and 256 (27%) received Medicaid. Compared with commercially-insured patients, use of DMTs was lower among Medicaid patients at 6 months preconception (25.4% vs 40.4%; p < 0.001), with similar patterns observed both during pregnancy and postpartum. Overall, prevalence of DMT use declined sharply during pregnancy, from 36.3% of patients in the 6 months preconception to 17.9%, 5.3%, and 5.8% in trimesters 1, 2 and 3, respectively. Postpartum DMT utilization increased to 20.9% at 0-3 months and 24.4% at 4-6 months. Of all patients in the preconception period, the most frequently used DMTs were glatiramer acetate (14.3%), dimethyl fumarate (6.0%), interferon (5.2%), and natalizumab (4.9%). Due to small sample size, information was limited for anti-CD20s and alemtuzumab. The proportion of patients with any moderate/severe relapse declined over pregnancy (preconception, n = 82 [8.7%]; pregnancy, n = 25 [2.6%]), but increased postpartum (n = 94 [10.0%]). Of the 889 patients who stopped DMT during pregnancy, the risk of postpartum relapses was lower in the patients who resumed DMT postpartum (10/192) than in patients who did not (76/697) (5.2% vs 10.9%; odds ratio, 0.455 [95% confidence interval 0.216-0.860], p = 0.018). Cases of postpartum depression and anxiety were significantly lower in commercially-insured patients vs Medicaid patients (postpartum depression, 13.7% vs 27.0%, p < 0.01; postpartum anxiety, 16.3% vs 30.5%, p < 0.01). Conclusion: DMT utilization declined sharply during pregnancy; it gradually increased postpartum but remained below pre-pregnancy use. The proportion of pwMS experiencing a moderate/severe relapse and number of relapses declined over pregnancy but increased postpartum. Reinitiation of DMT during the postpartum period was associated with lower risk of relapses, supporting a role for early reinitiation of DMT postpartum.

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. 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. 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

Objective: To assess safety, tolerability, and efficacy of diroximel fumarate (DRF) in male patients compared with female patients in EVOLVE-MS-1. Background: Males with relapsing multiple sclerosis (RMS) have lower incidence (1:3), higher risk for poor prognosis, and faster disease progression than females. DRF is an oral fumarate for RMS with the same active metabolite as dimethyl fumarate (DMF). DRF is expected to have a safety/efficacy profile similar to DMF but demonstrated fewer gastrointestinal (GI)-related adverse events (AEs). Design/Methods: EVOLVE-MS-1 (NCT02634307) is a 2-year, phase 3 study of DRF in adults with RMS. Patients either entered as newly enrolled to DRF trials, or from the 5-week, randomized, head-to-head, double-blind, phase 3 EVOLVE-MS-2 study (NCT03093324) of DRF and DMF. Results: As of Jan-2022, 1057 patients (male, n=295; female, n=762) were enrolled. Baseline characteristics were generally similar between male and female patients. Overall, 7% of males and 8% of females discontinued treatment due to AEs. AEs occurred in 86% of males and 90% of females; serious AEs occurred in 15% and 11%, respectively. In males and females, GI AEs occurred in 29% and 33%, and flushing AEs occurred in 22% and 29%, respectively. Adjusted annualized relapse rate was 0.13 in both males (95% CI: 0.10–0.19) and females (95% CI: 0.11–0.15; 82.4% and 81.2% reductions vs 12 months before study entry, respectively [both p<0.0001]). Proportions of patients who were Gd+ lesion-free at Week 96 vs Baseline, respectively, were 88.1% vs 69.4% (males) and 92.3% vs 70.8% (females). Estimated proportions of patients free from confirmed disability progression at 96 weeks were similar: males, 90.7%; females, 90.0%. Conclusions: After 2 years of DRF exposure, both male and female patients with MS had similar safety, tolerability, and efficacy outcomes. These data suggest that, despite males tending to experience more aggressive disease, DRF is a suitable treatment strategy for this patient cohort. Disclosure: The institution of Dr. Wundes has received research support from Benaroya Research Institute . Dr. Lindsey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech. Dr. Lindsey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Banner Life Sciences. Dr. Lindsey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for TG Therapeutics. Dr. Lindsey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mapi. Dr. Lindsey has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Teva. The institution of Dr. Lindsey has received research support from Genentech. Hailu Chen has received personal compensation for serving as an employee of Biogen.com. Hailu Chen has received stock or an ownership interest from Biogen.com. Mr. Scaramozza has received personal compensation for serving as an employee of Biogen. Mr. Scaramozza has stock in Biogen. Mr. Scaramozza has received intellectual property interests from a discovery or technology relating to health care. Filipe Branco has received personal compensation for serving as an employee of Biogen. Filipe Branco has received stock or an ownership interest from Biogen. Dr. Castro-Borrero has received personal compensation for serving as an employee of BIOGEN. Dr. Castro-Borrero has received stock or an ownership interest from BIOGEN. Dr. Shankar has received personal compensation for serving as an employee of Biogen. Dr. Shankar has stock in Biogen. Dr. Naismith has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Naismith has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Bristol Myers Squib. Dr. Naismith has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech. Dr. Naismith has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genzyme. Dr. Naismith has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Lundbeck. Dr. Naismith has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for NervGen. Dr. Naismith has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Abata Therapeutics. Dr. Naismith has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for GW Therapeutics. Dr. Naismith has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen. Dr. Naismith has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Horizon Therapeutics. Dr. Naismith has received personal compensation in the range of $500-$4,999 for serving as a Consultant for TG Therapeutics. Dr. Naismith has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Celltrion. Dr. Naismith has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Naismith has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for NEJM Journal Watch.

Objective: To assess pregnancy outcomes and DMF exposure in a completed international registry (NCT01911767, TecGistry) of women with MS exposed to dimethyl fumarate (DMF). Background: Oral delayed-release DMF has a favorable benefit-risk profile in treating people with multiple sclerosis (PwMS) and should be used in pregnant women only if the potential benefits outweigh the potential risk to the fetus. Design/Methods: TecGistry includes women with MS exposed to DMF from the first day of their last menstrual period before conception or during pregnancy, with data collected at enrollment, 6–7 months gestation, 4 weeks after estimated due date, and at 4, 12, and 52 weeks postpartum. Outcomes collected included live births, pregnancy loss, ectopic/molar pregnancies, birth defects and anomalies, and infant or maternal death after delivery. Gestational weight was classified by percentile (<10th, 10th–90th, >90th), which was based on standardized growth charts. Results: As of 13 May 2022, 397 women with MS were enrolled, with a median age of 32 years (range: 19, 43). Median gestation week at first DMF exposure was 1 (range: 0, 13) and at enrollment was 10 (range: 0, 39). Median duration of gestational DMF exposure was 5 weeks (range: 0, 40). Among DMF discontinuations, one was due to serious AE. Fifteen (3.8%) spontaneous abortions occurred. Of the 360 live births, 323 (90%) were full term and 37 (10%) were premature (<37 weeks). Gestational weight data was available for 282 infants, in which 32 (11.3%) were classified as small, 240 (85.1%) as appropriate, and 10 (3.5%) as large. One neonatal death and no maternal deaths occurred. Overall, 13 (3.6%) infants had adjudicator-confirmed MACDP birth defects and 8 (2.2%) had adjudicator-confirmed EUROCAT birth defects. Conclusions: Dimethyl fumarate exposure during pregnancy did not adversely affect pregnancy outcomes, with no increased incidence of birth defects and no increased rate of spontaneous abortion. Disclosure: Kerstin Hellwig has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Teva . Kerstin Hellwig has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen . Kerstin Hellwig has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis . Kerstin Hellwig has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche . Kerstin Hellwig has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck . Kerstin Hellwig has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genzyme . Kerstin Hellwig has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bayer . Kerstin Hellwig has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS. Kerstin Hellwig has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen . Kerstin Hellwig has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for INC research . Kerstin Hellwig has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis . Kerstin Hellwig has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche . Kerstin Hellwig has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Merck . Kerstin Hellwig has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen . Kerstin Hellwig has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bayer . The institution of Kerstin Hellwig has received research support from Roche . The institution of Kerstin Hellwig has received research support from Merck . The institution of Kerstin Hellwig has received research support from Biogen. The institution of Kerstin Hellwig has received research support from Genzyme . The institution of Kerstin Hellwig has received research support from Novartis . The institution of Kerstin Hellwig has received research support from TEVA. Dr. Rog has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Rog has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Rog has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Celgene. Dr. Rog has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Rog has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Dr. Rog has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for MedDay. Dr. Rog has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi Genzyme. Dr. Rog has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Janssen-Cilag. Dr. Rog has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Dr. Rog has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Dr. Rog has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck. Dr. Rog has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Dr. Rog has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi Genzyme. The institution of Dr. Rog has received research support from Actelion. The institution of Dr. Rog has received research support from Biogen. The institution of Dr. Rog has received research support from MedDay. The institution of Dr. Rog has received research support from Merck. The institution of Dr. Rog has received research support from Mitsubishi. The institution of Dr. Rog has received research support from Novartis. The institution of an immediate family member of Dr. Rog has received research support from Sanofi Genzyme. The institution of Dr. Rog has received research support from TG Therapeutics. Dr. Rog has received research support from Janssen-Cilag. Dr. McGuigan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. McGuigan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. McGuigan has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. The institution of Dr. McGuigan has received research support from Biogen. The institution of Dr. McGuigan has received research support from Novartis. The institution of Dr. McGuigan has received research support from Roche. Dr. Houtchens has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Houtchens has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche . Dr. Houtchens has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Houtchens has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Serono. Dr. Houtchens has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Cravath. Dr. Houtchens has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Beasley . Dr. Houtchens has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Biogen. The institution of Dr. Houtchens has received research support from Genzyme. The institution of Dr. Houtchens has received research support from Biogen. The institution of Dr. Houtchens has received research support from Genentech. Denise Bruen has received personal compensation for serving as an employee of Can Do MS. Denise Bruen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Denise Bruen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS. Denise Bruen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi Genzyme. Denise Bruen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EMD Serono. Denise Bruen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for TG Therapeutics. Oksana Mokliatchouk has received personal compensation for serving as an employee of Biogen. Oksana Mokliatchouk has received stock or an ownership interest from Biogen. Filipe Branco has received personal compensation for serving as an employee of Biogen. Filipe Branco has received stock or an ownership interest from Biogen. Dr. Levin has received personal compensation for serving as an employee of Biogen. Dr. Levin has received stock or an ownership interest from Biogen. Dr. Lin has received personal compensation for serving as an employee of Biogen. Dr. Lin has stock in Biogen.

Aims Health care providers (HCPs) treating multiple sclerosis (MS) in clinical practice have numerous disease-modifying therapies (DMTs) to consider when evaluating treatment options. This study assessed the treatment preferences of HCPs in the United States, both direct (explicit) and derived (explicit and implicit), when selecting MS DMTs based on clinical and logistical treatment attributes.Materials and methods A 45-minute web-enabled questionnaire was administered to HCPs who manage patients with MS to assess the importance of treatment attributes. HCPs were recruited through an online panel. This study examined treatment attributes relevant to treatment decisions in MS, with a focus on the burden to HCPs and their staff, as well as HCP attitudes toward various aspects of MS care such as diagnosis, treatment prioritization, and ease of initiating or switching DMTs. The study also employed a discrete choice experiment (DCE) to assess direct and derived treatment preferences.Results The study recruited 145 HCPs. Direct assessments (a score of greater than 7.0 was considered important) suggested that safety (mean importance rating = 7.8/9) and relative risk reduction in relapses (7.6/9) and disability progression (7.5/9) were most important when selecting DMTs. In contrast, derived importance from the DCE (higher points corresponding to greater importance) suggested that logistical attributes such as dose frequency (mean relative attribute importance = 17.5%), dose titration (10.3%), formulation (9.4%), and volume of calls (9.1%) were important considerations, along with efficacy (16.5%), safety (9.8%), and gastrointestinal tolerability (9.4%).Limitations This study may have been subject to selection bias due to the application of eligibility criteria, the convenient sampling recruitment methodology, and recruitment of HCPs with internet access.Conclusion In the direct assessment, clinical attributes were chosen as the most important treatment attributes by HCPs. However, in the DCE, derived treatment decisions rated logistical attributes as also being as important in treatment choice. In this study, researchers aimed to understand what multiple sclerosis (MS) neurologists, nurse practitioners, and physician assistants think is most important when choosing medicines for their patients. They surveyed 145 health care providers (HCPs) in the United States for this study. The HCPs reported that safety and reducing the risk of relapses and disability were most important when selecting medicines. Additionally, the researchers used a method called a discrete choice experiment to determine the relative importance of medication characteristics to HCPs. They found that additional factors, such as how often the medicine needs to be taken, how it is given, and how easy it is to use, were also very important. The study may not represent the opinions of all HCPs due to the number of participants and participation criteria.

Objective: 1. To report pregnancy outcomes from women with multiple sclerosis (MS) exposed to diroximel fumarate (DRF) during pregnancy in EVOLVE-MS-1. 2. To describe a prospective, international pregnancy registry of women with MS (BlossoMS). Background: DRF, a next-generation oral fumarate approved for relapsing forms of MS, has the same active metabolite, monomethyl fumarate, and fewer gastrointestinal AEs compared with dimethyl fumarate (DMF). While many patients with MS are women of childbearing potential, there are limited data on developmental risks associated with use of DRF before and during pregnancy. Design/Methods: 1. EVOLVE-MS-1 (NCT02634307) is an open-label, 96-week study assessing DRF safety, tolerability, and efficacy. Any female found to be pregnant while participating in EVOLVE-MS-1 was discontinued from study treatment, but the pregnancy was followed until completion or termination. 2. BlossoMS, anticipated to begin in 2023, aims to evaluate effects of DRF on pregnancy outcomes and compare women with MS exposed to DRF with those exposed to other disease-modifying therapies (DMTs), unexposed to DMTs, and women without MS. Results: Overall, 9 patients in EVOLVE-MS-1 had pregnancies; median (range) age at enrollment was 28 (19–33, n=9) years, median (range) overall DRF exposure in EVOLVE-MS-1 was 306.5 (12–431, n=8) days, and median (range) duration of DRF exposure during pregnancy was 46 (29–101, n=6) days. Of 9 pregnancies, 6 outcomes were live birth without congenital abnormality, including one set of twins; 1 was an elective termination with no known fetal defects; and 2 were spontaneous abortion. Conclusions: We report pregnancy outcomes in women exposed to DRF during pregnancy. It is important to better understand potential pregnancy-related risks associated with use of DRF to help providers and patients with medical decision-making. The BlossoMS registry will provide essential information on the risk of birth defects, congenital abnormalities, and pregnancy outcomes among women with MS exposed to DRF during pregnancy. Disclosure: Dr. Houtchens has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Houtchens has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche . Dr. Houtchens has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Houtchens has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Serono. Dr. Houtchens has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Cravath. Dr. Houtchens has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Beasley . Dr. Houtchens has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Biogen. The institution of Dr. Houtchens has received research support from Genzyme. The institution of Dr. Houtchens has received research support from Biogen. The institution of Dr. Houtchens has received research support from Genentech. The institution of Dr. Wundes has received research support from Benaroya Research Institute . Dr. Osborne has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Alexion. Dr. Osborne has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Biogen. Dr. Osborne has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Bristol Myer Squibb. Dr. Osborne has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Horizon. Dr. Osborne has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Peter Angelos Law Firm. Dr. Osborne has received publishing royalties from a publication relating to health care. Dr. Bozin has received personal compensation for serving as an employee of Biogen. Dr. Bozin has received personal compensation for serving as an employee of Arvelle Therapeutics. Dr. Bozin has stock in Biogen. Filipe Branco has received personal compensation for serving as an employee of Biogen. Filipe Branco has received stock or an ownership interest from Biogen. Hailu Chen has received personal compensation for serving as an employee of Biogen.com. Hailu Chen has received stock or an ownership interest from Biogen.com. Dr. England has received personal compensation for serving as an employee of Biogen. Dr. England has stock in Biogen. Ms. Gerber has received personal compensation for serving as an employee of Biogen. Ms. Gerber has stock in Biogen. Dr. Levin has received personal compensation for serving as an employee of Biogen. Dr. Levin has received stock or an ownership interest from Biogen. Dr. Lin has received personal compensation for serving as an employee of Biogen. Dr. Lin has stock in Biogen. Mr. Scaramozza has received personal compensation for serving as an employee of Biogen. Mr. Scaramozza has stock in Biogen. Mr. Scaramozza has received intellectual property interests from a discovery or technology relating to health care. Kerstin Hellwig has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Teva . Kerstin Hellwig has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen . Kerstin Hellwig has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis . Kerstin Hellwig has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche . Kerstin Hellwig has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck . Kerstin Hellwig has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genzyme . Kerstin Hellwig has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bayer . Kerstin Hellwig has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS. Kerstin Hellwig has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen . Kerstin Hellwig has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for INC research . Kerstin Hellwig has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis . Kerstin Hellwig has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche . Kerstin Hellwig has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Merck . Kerstin Hellwig has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen . Kerstin Hellwig has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bayer . The institution of Kerstin Hellwig has received research support from Roche . The institution of Kerstin Hellwig has received research support from Merck . The institution of Kerstin Hellwig has received research support from Biogen. The institution of Kerstin Hellwig has received research support from Genzyme . The institution of Kerstin Hellwig has received research support from Novartis . The institution of Kerstin Hellwig has received research support from TEVA.

[email protected] (B. Iyoma). Même sécurité d'emploi et d'efficacité du diroximel fumarate (DRF) que le diméthylfumarate (DMF) dont il a le même métabolite actif mais avec une meilleure tolérance GI pour le DRF. Évaluer les flushs et les EI qui leurs sont liés ainsi que les EI GI chez les patients initiant le DRF dans l'étude EVOLVE-MS-1 (groupe de novo). EVOLVE-MS-1 est une étude de phase 3 ouverte, de 96 semaines, évaluant la sécurité d'emploi et l'efficacité du DRF chez des adultes atteints de SEP-RR. Les patients inclus ont soit initié le DRF (groupe de novo) soit complété l'étude EVOLVE-MS-2, phase 3 randomisée, en aveugle, évaluant le DRF ou le DMF pendant 5 semaines (groupes rollover). Les résultats du groupe de novo sur les flushs/EI liés aux flushs et les EI GI seront présentés. Dans le groupe de novo sont inclus 593 patients (56,1 %). Des EI sont survenus chez 519 patients (87,5 %). Des flushs/EI liés aux flushs sont observés chez 49,2 % des patients ; la plupart, légers/modérés, survenant le premier mois de DRF. Le DRF a été arrêté chez 4 patients. Des EI GI sont survenus chez 33,7 % des patients ; la plupart, légers/modérés, survenant le premier mois de DRF. Le DRF a été arrêté chez 5 patients. Dix-sept pour cent et 46 % des participants présentant un EI (flushs et GI, respectivement) ont reçu un traitement concomitant. L'incidence globale des flushs/EI liés aux flushs et EI GI dans les groupes rollover est faible. Peu de participants ont rapporté ces EI après 5 mois de traitement. Ces données sont en adéquation avec le profil de tolérance connu du DRF. Flush/EI liés aux flushs et EI GI sont fréquents, souvent légers/modérés et survenant le premier mois sous DRF. Peu d'arrêts de traitement sont liés aux flushs ou EI GI.

Objective: To evaluate disease-modifying therapy (DMT) utilization for the treatment of multiple sclerosis (MS) before, during and after pregnancy. Background: Pregnancy is a common consideration for women with MS; MS onset is typically between the ages of 20–45 years, i.e., during the child-bearing years. Pregnancy and postpartum care are a significant factor influencing DMT selection for many patients with MS. To date, few DMTs are considered safe to continue during pregnancy and real-world treatment patterns before, during and after pregnancy remain uncharacterized. Design/Methods: In this retrospective, observational study, the US MarketScan Commercial and Medicaid claims database was assessed for female patients aged 18–55 years, with an MS diagnosis and ≥1 delivery-related inpatient or outpatient claims from 01 January 2016–30 April 2021. Results: A cohort of 944 patients was identified; 688 (73%) were commercially-insured and 256 (27%) received Medicaid. Prevalence of DMT use declined sharply during pregnancy, from 36.3% of patients in the 6 months prior to pregnancy (pre-pregnancy) to 17.9%, 5.3% and 5.8% in trimesters (T) 1, 2 and 3, respectively. Postpartum DMT utilization increased to 20.9% at 0–3 months and 24.4% at 4–6 months. Of all patients (n=944) in the pre-pregnancy period, the most frequently used DMTs were glatiramer acetate (15.0%), dimethyl fumarate (6.4%), interferon (5.4%) and natalizumab (5.2%). Of patients treated with any DMT in T1, patients were more likely to continue treatment into T3 if treated with natalizumab and glatiramer acetate (60.9% [T1] to 10.9% [T3] and 54.8% [T1] to 20.7% [T3], respectively) compared with interferon (36.7% [T1] to 8.2% [T3]), fingolimod (35.1% [T1] to 8.1% [T3]), dimethyl fumarate (28.1% [T1] to 7.0% [T3]), or ocrelizumab (6.7% [T1] to 0% [T3]). Conclusions: DMT utilization declined sharply during pregnancy; it gradually increased postpartum but remained below pre-pregnancy use. Infusibles administered every 6–12 months (e.g., anti-CD20 medications) may have been underestimated. Disclosure: The institution of Dr. Shah has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. The institution of Dr. Shah has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TG Therapeutics. Dr. Shah has received personal compensation in the range of $5,000-$9,999 for serving as a Educational Speaker with Rocky Mountain MS Center. Dr. Bove has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Bove has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon. Dr. Bove has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Bove has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EMD Serono. Dr. Bove has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genzyme Sanofi. Dr. Bove has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Bove has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TG Therapeutics. Dr. Bove has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Jansen. Dr. Bove has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. The institution of Dr. Bove has received research support from Biogen. The institution of Dr. Bove has received research support from Roche Genentech. The institution of Dr. Bove has received research support from Novartis. Dr. Applebee has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen. Dr. Applebee has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Genentech. Dr. Applebee has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genzyme. Dr. Applebee has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Serono. Dr. Applebee has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Horizon. Dr. Applebee has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bristol Myers Squibb. Ms. Bawden has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Biogen. Ms. Bawden has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biohaven. Ms. Bawden has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Banner Life Sciences. Ms. Bawden has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for TG therapeutics. Ms. Fine has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Biogen. Ms. Fine has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Abbvie. Mrs. Avila has received personal compensation for serving as an employee of Biogen. Mrs. Avila has stock in Biogen. Dr. Belviso has received personal compensation for serving as an employee of Biogen. Filipe Branco has received personal compensation for serving as an employee of Biogen. Filipe Branco has received stock or an ownership interest from Biogen. Dr. Fong has received personal compensation for serving as an employee of Biogen. Dr. Lewin has received personal compensation for serving as an employee of Biogen. Dr. Lewin has stock in Biogen. Ms. LIU has received personal compensation for serving as an employee of Biogen . Ms. LIU has stock in Biogen. Dr. England has received personal compensation for serving as an employee of Biogen. Dr. England has stock in Biogen. Dr. Vignos has stock in Biogen. Dr. Vignos has received personal compensation in the range of $100,000-$499,999 for serving as a Employee with Biogen.

ObjectiveReport pregnancy outcomes from diroximel fumarate (DRF)-exposed women with multiple sclerosis (MS) in EVOLVE-MS-1, and describe a prospective, international pregnancy registry of women with MS (BlossoMS).BackgroundDRF is a next-generation oral fumarate approved for relapsing forms of MS. There are limited data on developmental risks associated with DRF use before and during pregnancy.Design/MethodsEVOLVE-MS-1 (NCT02634307) is an open-label, 96-week study assessing DRF. Any female in EVOLVE-MS-1 found to be pregnant was discontinued from study treatment; the pregnancy was followed until completion/termination. BlossoMS (anticipated 2023 start) will evaluate pregnancy outcomes in DRF-treated women, compared with those on other disease-modifying therapies (DMTs), no DMTs, and women without MS.ResultsOverall, 9 patients in EVOLVE-MS-1 had pregnancies; median (range) age at enrollment was 28 (19–33, n=9) years, overall DRF exposure in EVOLVE-MS-1 was 306.5 (12–431, n=8) days, and duration of DRF exposure during pregnancy was 46 (29–101, n=6) days. Of 9 pregnancies, 6 live births without con- genital abnormality, 1 elective termination with no known fetal defects, and 2 spontaneous abortions were observed.ConclusionsWe report pregnancy outcomes in women exposed to DRF during pregnancy. BlossoMS will provide essential information among DMF-exposed women during pregnancy. Supported: Biogen.

La SEP-pédiatrique représente environ 5 % des cas. Son évolution est souvent plus active que chez l'adulte. Le profil d'efficacité et sécurité du DMF, établi chez l'adulte, est inconnu chez l'enfant. L'étude CONNECT a comparé l'efficacité et la sécurité du DMF et de l'interféron bêta-1a (IFNβ-1a) intramusculaire chez des patients présentant une SEP d'apparition pédiatrique à la semaine (S) 96. CONNECT est une étude ouverte, randomisée, multicentrique, avec contrôle actif, chez des patients présentant une SEP récurrente-rémittente âgés de 10 à < 18 ans traités par DMF ou IFNβ-1a pendant 96S. Le critère d'évaluation principal était la proportion de patients sans nouvelles lésions ou lésions élargies (N/NE) hyper-intenses en T2 à S96 par rapport à l'inclusion. Les critères d'évaluation secondaires incluaient la proportion de patients sans poussée et les événements indésirables (EI). Au total, 150 patients ont été inclus (78 DMF et 72 IFNβ-1a) ; l'âge médian était 15 ans. La proportion de patients sans N/NE hyper-intenses en T2 à S96 était de 16 % pour le DMF vs 5 % pour l'IFNβ-1a. À S96. Les EI les plus fréquents observés chez les patients traités par DMF étaient les douleurs gastro-intestinales et bouffées congestives ; chez les patients traités par IFNβ-1a, il s'agissait de syndromes pseudo-grippaux et céphalées. Un plus grand nombre de patients traités par DMF étaient exempts de lésions T2N/NE à S96 comparés à ceux traités par IFNβ-1a. Le taux annualisé de poussée ajusté était également plus faible pour le DMF vs IFNβ-1a à S96. D'une manière générale, le profil de sécurité et de tolérance chez les patients pédiatriques était conforme à celui observé dans la population adulte.

To describe effectiveness of delayed-release dimethyl fumarate (DMF) for patients with relapsing-remitting multiple sclerosis (RRMS) previously treated with teriflunomide who switched for efficacy or non-efficacy reasons.

IntroductionDimethyl fumarate (DMF) is not recommended for use during pregnancy and should only be used if the potential benefit justifies the potential foetal risk. Given limited pregnancy data, the UK and Ireland have enrolled DMF-exposed pregnant women in an ongoing international registry assessing pregnancy outcomes. Generally, pregnancies end in live birth (62%), abortion (22%), or foetal loss (16%), with similar rates in MS patients.MethodsPregnant women with MS exposed to DMF since the first day of their last menstrual period before conception/during pregnancy were included. UK/Ireland Coordinating Centres liaise directly with patients and healthcare providers.ResultsAs of May 2020, 345 patients (18 UK/Ireland) were enrolled. Of the reported 351 pregnancy outcomes (18 UK/Ireland), 277 (79%) represented live births (17 UK/Ireland) and 74 (21%) foetal loss. Of infants with known gestational age (n=274), 249 births (91%) were full-term (17 UK/Ireland) and 25 (9%) premature (<37 weeks). There were 17 spontaneous abortions (1 each ectopic and molar pregnancy) and 1 foetal death (at >28 weeks). No infant or maternal deaths were reported. Ten infants (4%) (2 UK/Ireland) had confirmed birth defects.ConclusionsObserved safety signals were consistent with MS and general populations.SupportBiogen. Disclosures: Included on poster 81david.rog@srft.nhs.uk

IntroductionDimethyl fumarate (DMF) is not recommended during pregnancy and should only be used if the potential benefit justifies potential foetal risk. Given limited pregnancy data, the UK and Ireland have enrolled DMF-exposed pregnant women in an ongoing international registry assessing pregnancy outcomes. In the general population, 62% of pregnancies end in live birth, 22% in abortion, and 16% in foetal loss, with similar rates in multiple sclerosis (MS) patients.MethodsWomen with MS exposed to DMF since the first day of their last menstrual period before con- ception/during pregnancy were included. UK/Ireland Coordinating Centres liaised directly with patients and healthcare providers.ResultsAs of March 2021, 403 patients (19 UK/Ireland) were enrolled. Of 350 reported pregnancy outcomes (19 UK/Ireland), 329 (94%) represented live births (100% UK/Ireland). Of 326 infants with known gestational age,298 births (91%) were full-term (100% UK/Ireland) and 28 (9%) premature (<37 weeks). Of the 21 (6%) cases of foetal loss, 19 were spontaneous abortions (1 each ectopic and molar pregnancy) and 2 foetal deaths (>28 weeks). There was one neonatal death. Nine infants (2 UK/Ireland) had EUROCAT-confirmed birth defects.ConclusionsThe observations are consistent with MS and general populations.SupportBiogen. Disclosures on poster.

DRF et DMF sont métabolisés en métabolite actif identique, le monométhyl-fumarate. L'exposition au monométhyl-fumarate est bioéquivalente (efficacité/sécurité similaires entre DMF et DRF), avec une tolérance gastro-intestinale amélioré vs DMF. L'objectif de cette analyse est de décrire, pour la première fois, les bouffées congestives et EI liés à ces bouffées congestives apparus sous DMF vs DRF. Une analyse post-hoc des bouffées congestives et des EI apparus sous traitement (EIAT), liés aux bouffées congestives a été conduite chez des patients présentant une SEP-RR ayant reçu le DRF ou le DMF pendant 5 semaines dans l'étude de phase 3 randomisée en double aveugle EVOLVE-MS-2 (NCT03093324). Les EIAT ont été recueillis par les investigateurs lors de chaque visite de l'étude. Dans EVOLVE-MS-2, 253 et 251 patients ont reçu respectivement ≥ 1 dose de DRF ou de DMF. L'incidence des bouffées congestives était plus faible avec le DRF (46 %) vs DMF (55 %). Toutes les bouffées congestives étaient de sévérité légère ou modérée avec le DRF. La majorité des événements sont survenus au cours de la première semaine de traitement. La durée médiane des bouffées congestives résolues était plus courte dans le groupe DRF vs DMF. L'étude EVOLVE-MS-2 n'a pas été conçue pour évaluer les différences de bouffées congestives. Bien que chez les patients traités par DRF, des bouffées congestives soient survenues chez un nombre plus faible de patients, l'incidence des bouffées congestives avec le DRF se situait généralement dans la plage attendue en comparaison aux taux rapportés dans les essais cliniques contrôlés sur le DMF. La signification clinique des changements observés est incertaine et des études en vie réelle supplémentaires sont nécessaires.

Importance With few approved multiple sclerosis therapies in the pediatric population, there is a need for further approved treatment options. Limited data exist for dimethyl fumarate (DMF) treatment in pediatric-onset multiple sclerosis (POMS). Objective To compare the efficacy, safety, and tolerability of DMF vs intramuscular interferon β-1a (IFNβ-1a) in POMS. Design, Setting, and Participants The CONNECT study was an active-controlled, open-label, rater-blinded 96-week randomized clinical trial in patients with POMS aged 10 to less than 18 years treated between August 2014 and November 2020. Data were analyzed from January through October 2021. Interventions Patients were randomized to DMF or IFNβ-1a. Main Outcomes and Measures The primary end point was the proportion of patients free of new or newly enlarging (N or NE) T2 hyperintense lesions at week 96 among trial completers. Secondary end points included number of N or NE T2 lesions, proportion of patients free of relapse, annualized relapse rate (ARR), and safety. The estimated proportion of participants who were relapse free up to week 96 was calculated based on the Kaplan-Meier method. Adjusted ARR was obtained from a negative binomial regression adjusted for baseline relapse rate, baseline Expanded Disability Status Scale (EDSS) score, and age group. Results Among 150 patients with POMS in the intention-to-treat (ITT) population (median [range] age, 15 [10-17] years; 101 [67.3%] female patients), 78 individuals received DMF and 72 individuals received IFNβ-1a. At week 96, the proportion of patients with no N or NE T2 hyperintense lesions among 103 trial completers was 16.1% (95% CI, 8.0%-27.7%) for DMF vs 4.9% (95% CI, 0.6%-16.5%) for IFNβ-1a, and in a sensitivity analysis among the ITT population, the proportions were 10 patients receiving DMF (12.8%) vs 2 patients receiving IFNβ-1a (2.8%). The estimated proportion of patients who remained relapse free at week 96 was 66.2% for DMF vs 52.3% for IFNβ-1a. Adjusted ARR (95% CI) at week 96 was 0.24 (95% CI, 0.15-0.39) for DMF vs 0.53 (95% CI, 0.33-0.84) for IFNβ-1a; the rate ratio for DMF vs IFNβ-1a was 0.46 (95% CI, 0.26-0.80; P = .006). The number of treatment-emergent adverse events (TEAEs; 74 patients [94.9%] vs 69 patients [95.8%]), serious TEAEs (18 patients [23.1%] vs 21 patients [29.2%]), and treatment discontinuations due to TEAEs (5 patients [6.4%] vs 8 patients [11.1%]) was similar for DMF vs IFNβ-1a. Conclusions and Relevance This study found that more pediatric patients with POMS treated with DMF were free of new or newly enlarging T2 lesions and that the adjusted ARR was lower among these patients compared with those treated with interferon β-1a. DMF was well tolerated. Trial Registration ClinicalTrials.gov Identifier: NCT02283853