Delayed-Release Dimethyl Fumarate Safety and Efficacy in Pediatric Patients With Relapsing-Remitting Multiple Sclerosis.

Raed Alroughani,Xiaomei Peng,Martin Valis,Astrid Blaschek,Peter Huppke,Maria Mazurkiewicz-Beldzinska,Gregory Aaen,Joe Pultz,Vanessa Beynon

doi:10.3389/fneur.2020.606418

Abstract

Background: Pediatric multiple sclerosis (MS) is rare: only 1.5–5% of MS cases are diagnosed before 18 years of age, and data on disease-modifying therapies (DMTs) for pediatric MS are limited. The CONNECTED study assessed the long-term safety and efficacy of treatment with delayed-release dimethyl fumarate (DMF), an oral MS DMT, in pediatric patients with MS.Methods: CONNECTED is the 96-week extension to FOCUS, a 24-week phase 2 study of patients aged 13–17 years; participants received DMF 240 mg twice daily. Endpoints included (primary) incidence of adverse events (AEs), serious AEs, and DMF discontinuations due to an AE, and (secondary) T2 hyperintense lesion incidence by magnetic resonance imaging and annualized relapse rate (ARR).Results: Twenty participants [median (range) age, 17 (14–18) years; 65% female] who completed FOCUS enrolled into CONNECTED; 17 (85%) completed CONNECTED. Eighteen participants (90%) experienced AEs: the most frequent was flushing (25%). None experienced infections or fever related to low lymphocyte counts. Three participants experienced four serious AEs; none led to DMF discontinuation. Twelve of 17 participants (71%) had no new/newly enlarged T2 lesions from weeks 16–24, two (12%) had one, and one each (6%) had two, three, or five or more lesions [median (range), 0 (0–6)]. Over the full 120-week treatment period, ARR was 0.2, an 84.5% relative reduction (n = 20; 95% confidence interval: 66.8–92.8; p < 0.0001) vs. the year before DMF initiation.Conclusions: The long-term safety and efficacy observed in CONNECTED was consistent with adults, suggesting pediatric and adolescent patients with MS might benefit from DMF treatment.

Highlights

Pediatric multiple sclerosis (MS) is a rare disease, with only 1.5–5% of all MS cases diagnosed before 18 years of age [1,2,3,4,5,6,7,8,9]
To week 24 and no additional new or newly enlarged lesions from week 64 to week 72. In this 96-week extension study of dimethyl fumarate (DMF) treatment in pediatric patients with MS, DMF showed an acceptable long-term safety profile in pediatric and adolescent participants, consistent with that observed in adults
No participants died during the study, discontinued DMF treatment due to an adverse event (AE), or withdrew from the study due to an AE

Summary

Introduction

Pediatric multiple sclerosis (MS) is a rare disease, with only 1.5–5% of all MS cases diagnosed before 18 years of age [1,2,3,4,5,6,7,8,9]. At present, starting treatment early in the disease course is recommended [13, 14], but adequate long-term safety and efficacy data on DMTs for the pediatric population are limited, resulting in a shortage of approved MS-specific treatment options in this patient population [15]. Fingolimod is the only MS therapy currently approved by both the US Food and Drug Administration and the European Medicines Agency for use in pediatric patients 10–17 years of age [22] on the basis of the positive outcome of a randomized controlled trial [23]. Pediatric multiple sclerosis (MS) is rare: only 1.5–5% of MS cases are diagnosed before 18 years of age, and data on disease-modifying therapies (DMTs) for pediatric MS are limited. The CONNECTED study assessed the long-term safety and efficacy of treatment with delayed-release dimethyl fumarate (DMF), an oral MS DMT, in pediatric patients with MS

Methods

Results

Conclusion