Relapse during the washout period predicts time to relapse after switching to cladribine.

Introduction: People with relapsing-remitting multiple sclerosis (RRMS) commonly switch between disease-modifying therapies (DMTs). Identifying predictors of relapse outcomes when switching to more recently approved therapies such as cladribine could improve outcomes. Aim(s): This study aimed to characterise relapse activity and determine predictors of relapse occurrence in the first year of cladribine treatment, after switching from other DMTs. Method(s): We identified patients with RRMS from the MSBase Registry who switched to cladribine from five prior DMT groups (pDMT; interferon-beta/glatiramer acetate, dimethyl fumarate, teriflunomide, fingolimod or natalizumab). Relapse occurrence during the washout and in the first year of cladribine were compared between pDMTs and washout duration groups (<1 month, 1-2 months, or 2-6 months). Cox proportional hazard regression models were used to analyse time to first relapse in the first year of cladribine therapy. Result(s): In a cohort of 333 patients with a mean washout duration of 43.1 days, 17 (5.1%) relapsed during the washout period and 24 (7.2%) relapsed within one year of starting cladribine. Of those who relapsed during their washout period, seven (41.2%) also relapsed on cladribine, compared to 5.4% of those who did not experience a washout relapse. In the adjusted survival model, relapse on cladribine was predicted by washout relapse (hazard ratio [HR]=7.18, 95% confidence interval [CI] = 1.48-34.88, p=0.015) and younger age (HR=0.96, 95% CI 0.93-0.99, p=0.038). Washout durations longer than two months increased relapse risk during the washout, but did not alter relapse risk on cladribine. There were no significant differences in relapse outcomes between pDMTs. Conclusion(s): Washout relapse and younger age are of prognostic relevance when switching to cladribine. Washout durations shorter than two months were associated with fewer washout relapses. Prospective studies are needed to assess if washout period red