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

Ludwig Kappos, Ernst Wilhelm Radue, Giancarlo Comi, Xavier Montalban, Helmut Butzkueven, Heinz Wiendl, Gavin Giovannoni, Hans Peter Hartung, Tobias Derfuss, Yvonne Naegelin, Till Sprenger, Nicole Mueller-Lenke, Sarah Griffiths, Philipp Von Rosenstiel, Rebecca Gottschalk, Ying Zhang, Frank Dahlke, Davorka Tomic

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Abstract

Objective: To investigate the effect of different natalizumab washout (WO) periods on recurrence of MRI and clinical disease activity in patients switching from natalizumab to fingolimod. Methods: In this multicenter, double-blind, placebo-controlled trial (TOFINGO), patients with relapsing-remitting multiple sclerosis (RRMS) 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 patients, 112 (78.9%) completed the study (8 weeks, n 5 41/50; 12 weeks, n 5 31/42; 16 weeks, n 5 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, gadoliniumenhancing T1 lesion 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 patients 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 patients experienced adverse events (mostly mild/moderate), with similar incidence across groups. No unusually severe relapses or opportunistic infections 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.

Original languageEnglish
Pages (from-to)29-39
Number of pages11
JournalNeurology
Volume85
Issue number1
DOIs
Publication statusPublished - Jul 7 2015

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ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Kappos, L., Radue, E. W., Comi, G., Montalban, X., Butzkueven, H., Wiendl, H., Giovannoni, G., Hartung, H. P., Derfuss, T., Naegelin, Y., Sprenger, T., Mueller-Lenke, N., Griffiths, S., Von Rosenstiel, P., Gottschalk, R., Zhang, Y., Dahlke, F., & Tomic, D. (2015). Switching from natalizumab to fingolimod: A randomized, placebo-controlled study in RRMS. Neurology, 85(1), 29-39. https://doi.org/10.1212/WNL.0000000000001706