Incidence of Relapse during the First 6 Months in a Cohort of Patients Switched to Dimethyl Fumarate

Background:

Dimethyl fumarate is the most recently approved oral DMT in the US. The safety profile of dimethyl fumarate is considered benign compared with that of natalizumab.

Natalizumab, although a highly effective disease-modifying treatment (DMT) for multiple sclerosis (MS), carries a serious risk of progressive multifocal leukencephalopathy (PML) ¹, although this risk may be stratified based on certain patient characteristics.

Many MS providers planned to switch their natalizumab patients with high risk to dimethyl fumarate once it became available. Patients with injection fatigue or with insufficient disease control on the interferons or glatiramir acetate were also considered good candidates for dimethyl fumarate.

Objectives:

To delineate patient characteristics associated with relapse during first six months on dimethyl fumarate therapy.

Methods:

Records review of patients with relapses significant enough to require rescue treatment during their first six months on dimethyl fumarate. Our clinic standard is three days of intravenous methylprednisolone (IVMP).

Results:

Most relapses occurred among female patients aged 30-40, in the third to fourth month after the switch, and among those whose prior DMT was natalizumab.

Discussion: Full response to dimethyl fumarate is not seen until six months². Relapse occurrence after natalizumab discontinuation rises substantially at ~3-5 months if no other DMT is started.¹Given that many natalizumab patients have aggressive disease, it should not surprise, though it does disappoint, to find that breakthrough disease may still occur when these patients are switched to dimethyl fumarate.

Our observations are of a small group of patients in one location. However, it is commonly observed that in the first few years after a drug's market approval we often see aspects of a drug that were not seen during clinical trials.

Conclusions:

Dimethyl fumarate is a welcome addition to DMT options. Counseling of patients prior to start of dimethyl fumarate should include a discussion of possible increased risk of relapse during the first six months on therapy. This appears to be particularly important for younger, female patients switched from natalizumab. Further characterization of patient response to dimethyl fumarate in the broader MS population is needed.

References:

1. Tysabri product information insert (2013).
2. Tecfidera product information insert (2013).