Disease activity outcomes with different washout periods after switching from natalizumab to an alternative disease-modifying therapy

Abstract

Background: Washout periods (WPs) are increasingly shortened due to concerns of disease rebound when patients on natalizumab are switched to alternative disease-modifying therapies (DMTs).

Objective: To characterize disease activity outcomes with different WPs when switching from natalizumab.

Methods: We conducted a retrospective review of patients switching from natalizumab in our MS clinics. Disease activity (relapse, new T2 lesions and/or gadolinium enhancing lesions) between different WPs (days): 0-30, 31-60, and 61-180 were compared, during the first year after switching from natalizumab. To determine predictors of disease activity when switching to any DMT, multivariate logistic regression analysis was used. Post hoc analyses were performed to evaluate the impact of individual DMTs on disease activity.

Results: 335 patients discontinued natalizumab with WP: 0-30 (n = 104), 31-60 (n = 113), and 61-180 (n = 136). Disease activity occurred in 44.2% of patients in the 0-30 WP group, 18.6% in the 31-60 WP group, and 27.2% in the 61-180 WP group. There was a significant decrease in odds of disease activity with longer WP when compared to the 0-30 group: 31-60 (OR 0.241, 95% CI 0.108-0.514, p value < 0.001), and 61-180 (OR 0.439, 95% CI 0.218-0.871, p value < 0.05).

Conclusions: Unexpectedly, in our study, patients who had the shortest WP 0-30 days had the most disease activity. Shortening WPs may not be enough to suppress disease activity post-natalizumab switch.

Keywords: Discontinuing therapy; Disease-modifying therapy; Multiple sclerosis; Natalizumab; Treatment sequencing; Washout.