Switching from natalizumab to fingolimod: A randomized, placebo-controlled study in XXXX .

@entity1 @entity75 @entity3780 @entity1292 @entity2287
OBJECTIVE: To investigate the effect of different natalizumab washout (WO) periods on recurrence of MRI and clinical disease activity in @entity1 switching from natalizumab to fingolimod. METHODS: In this multicenter, double-blind, placebo-controlled trial (TOFINGO), @entity1 with @entity3780 ( @entity3780 ) were randomized 1:1:1 to 8-, 12-, or 16-week WO followed by fingolimod treatment over 32 weeks from last natalizumab infusion (LNI). Brain MRI was performed at baseline and weeks 8, 12, 16, 20, and 24. RESULTS: Of 142 enrolled and randomized @entity1 , 112 (78.9%) completed the study (8 weeks, n = 41/50; 12 weeks, n = 31/42; 16 weeks, n = 40/50). Number (95% confidence interval [CI]) of active (new/newly enlarged T2) lesions from LNI through 8 weeks of fingolimod treatment (primary outcome) was similar in the 8-week (2.1 [1.7-2.6]) and 12-week WO groups (1.7 [1.3-2.2]) and higher in the 16-week WO group (8.2 [7.3-9.1]). During the WO period only, the number (95% CI) of active lesions increased with increasing WO duration (8 weeks, 0.4 [0.2-0.6]; 12 weeks, 2.1 [1.6-2.6]; 16 weeks, 3.6 [3.0-4.2]). Over the 24 weeks from LNI, @entity2287 -enhancing @entity75 counts were lower in the 8-week WO group (14.1 [5.67-22.53]) than in the 12-week (21.3 [1.41-41.19]) or 16-week (18.5 [8.40-28.60]) WO groups. More @entity1 were relapse-free in the 8-week (88%) and 12-week (91%) WO groups than the 16-week WO group (84%). Sixty-eight percent of @entity1 experienced adverse events (mostly mild/moderate), with similar incidence across groups. No unusually severe relapses or @entity1292 occurred. CONCLUSIONS: Initiating fingolimod therapy 8-12 weeks after natalizumab discontinuation is associated with a lower risk of MRI and clinical disease reactivation than initiation after 16-week WO. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for @entity1 with @entity3780 switching from natalizumab to fingolimod, shorter natalizumab WO periods are associated with less MRI disease activity than are longer WO periods.
