The optimal time between the cessation of one disease-modifying therapy (DMT) and initiation of another in relapsing-remitting multiple sclerosis (RRMS) is incompletely understood. Lymphopenia, an adverse effect of dimethyl fumarate (DMF), may prompt a washout period prior to initiating an alternate DMT to allow absolute lymphocyte count (ALC) recovery. We hypothesized that during the DMF-DMT treatment interval, there would be disease activity, either by MRI or clinical relapses, and that lymphopenia might be a risk factor.

A retrospective chart review was conducted, collecting data on demographics and disease activity (clinical relapse or MRI with new/enlarged T2/FLAIR or gadolinium-enhancing lesions in the brain or spinal cord). The DMF-DMT interval was defined as the time in years between stopping DMF and beginning a new DMT.

Of 109 patients, 32.1% experienced disease activity during the DMF-DMT interval. ALC decreased significantly during DMF therapy but was not associated with subsequent disease activity in the DMF-DMT interval (HR 1.09 [0.62, 1.91], p = 0.77). A Kaplan–Meier curve shows that the probability of experiencing disease activity was highest within the first year of DMF discontinuation, with the median time to first relapse after stopping DMF being 0.5 years.

Disease activity was most likely to occur early after DMF cessation but was not significantly related to ALC. Our data suggest that initiating a new DMT within 6 months of DMF cessation may reduce relapse risk and lesion accumulation in RRMS patients.