Dimethyl fumarate in the management of multiple sclerosis: appropriate patient selection and special considerations

Abstract

Delayed-release dimethyl fumarate (DMF), also known as gastroresistant DMF, is the most recently approved oral disease-modifying treatment (DMT) for relapsing multiple sclerosis. Two randomized clinical trials (Determination of the Efficacy and Safety of Oral Fumarate in Relapsing-Remitting MS [DEFINE] and Comparator and an Oral Fumarate in Relapsing-Remitting Multiple Sclerosis [CONFIRM]) demonstrated significant efficacy in reducing relapse rate and radiological signs of disease activity, as seen on magnetic resonance imaging. The DEFINE study also indicated a significant effect of DMF on disability worsening, while the low incidence of confirmed disability worsening in the CONFIRM trial rendered an insignificant reduction among the DMF-treated groups when compared to placebo. DMF also demonstrated a good safety profile and acceptable tolerability, since the most common side effects (gastrointestinal events and flushing reactions) are usually transient and mild to moderate in severity. Here, we discuss the place in therapy of DMF for individuals with relapsing multiple sclerosis, providing a tentative therapeutic algorithm to manage newly diagnosed patients and those who do not adequately respond to self-injectable DMTs. Literature data supporting the potential role of DMF as a first-line therapy are presented. The possibility of using DMF as switching treatment or even as an add-on strategy in patients with breakthrough disease despite self-injectable DMTs will also be discussed. Lastly, we argue about the role of DMF as an exit strategy from natalizumab-treated patients who are considered at risk for developing multifocal progressive leukoencephalopathy.

Keywords: dimethyl fumarate; multiple sclerosis; oral drugs; therapeutic algorithm.

Figure 1

Proposed treatment algorithm for treating R-MS with DMF. Notes: ^aConsider pregnancy desire; ^bconsider anti-VZV serological status, comorbidities, and concomitant non-MS treatments (eg, cardiac illnesses, antihypertensive drugs); cconsider anti-JCV serological status; ^dconsider anti-VZV serological status, latent tuberculosis, and HPV screening. Please note that this algorithm, though based on currently available literature data, represents the authors’ opinion only. Abbreviations: R-MS, relapsing multiple sclerosis; DMF, dimethyl fumarate; VZV, varicella zoster virus; JCV, John Cunningham virus; HPV, human papillomavirus; DMTs, disease-modifying treatments.