Disease recurrence linked to cessation of DMTs in patients with relapsing-remitting MS

In patients with relapsing-remitting multiple sclerosis, disease reactivation occurred within months of cessation of disease-modifying therapy but was reduced after starting a new treatment, according to a study published in Neurology.

“Treatment interruptions are common in patients with multiple sclerosis. Disease-modifying therapies (DMTs) may be stopped or switched for reasons of efficacy, tolerability, safety and preference,” Izanne Roos, PhD, of the department of neurology at Royal Melbourne Hospital in Australia, and colleagues wrote. “Treatment interruptions leave patients vulnerable to breakthrough disease activity.”

Roos and fellow researchers evaluated the return of disease activity in patients after cessation of DMTs by conducting a retrospective cohort study using MSBase and OFSEP observational registries. They included 14,213 participants with relapsing-remitting MS who stopped using a DMT after at least one year of treatment.

The primary study outcome was annualized relapse rate (ARR) in the 12 months after DMT discontinuation, stratified by patients who remained untreated and who started a new therapy. The secondary endpoint was predictors of first relapse and disability accumulation after treatment discontinuation.

Results showed that ARR began increasing 2 months after natalizumab cessation (month 2-4 ARR = 0.47; 95% CI, 0.43-0.51), but starting a subsequent therapy within 2 to 4 months reduced the magnitude of disease reactivation (mean ARR difference = 0.15; 95% CI, 0.08-0.22).

Rates of relapse increased overall following discontinuation of fingolimod (month 1-2 ARR = 0.8; 95% CI, 0.70-0.89) and stabilized faster in those who began a new DMT within 1 to 2 months (mean ARR difference = 0.14; 95% CI, –0.01 to –0.29).

Data additionally revealed that disease reactivation for other therapies was low and reduced further by starting another DMT within 10 months of treatment discontinuation. Researchers reported that higher ARR before cessation, female sex, younger age and higher score on the Expanded Disability Status Scale were predictors of relapse.

Overall, starting a new DMT reduced both the risk of relapse (HR = 0.76; 95% CI, 0.72-0.81) and disability accumulation (HR = 0.73; 95% CI, 0.65-0.8).

“To minimize the risk of disease reactivation, we therefore suggest that untreated intervals be minimized, while taking into account potential safety consideration during treatment sequencing,” Roos and colleagues wrote.