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

被引:96
作者
Kappos, Ludwig [1 ,2 ,3 ]
Radue, Ernst-Wilhelm [4 ]
Comi, Giancarlo [6 ]
Montalban, Xavier [7 ]
Butzkueven, Helmut [8 ]
Wiendl, Heinz [9 ]
Giovannoni, Gavin [10 ]
Hartung, Hans-Peter [11 ]
Derfuss, Tobias [1 ,2 ,3 ]
Naegelin, Yvonne [1 ,2 ,3 ]
Sprenger, Till [1 ,2 ,3 ,4 ,5 ]
Mueller-Lenke, Nicole [4 ]
Griffiths, Sarah [12 ]
von Rosenstiel, Philipp [13 ]
Gottschalk, Rebecca [14 ]
Zhang, Ying [13 ]
Dahlke, Frank [13 ]
Tomic, Davorka [13 ]
机构
[1] Univ Basel, Univ Hosp, Dept Med, CH-4003 Basel, Switzerland
[2] Univ Basel, Univ Hosp, Dept Clin Res, CH-4003 Basel, Switzerland
[3] Univ Basel, Univ Hosp, Dept Biomed, CH-4003 Basel, Switzerland
[4] Univ Basel, Univ Hosp, MIAC, CH-4003 Basel, Switzerland
[5] Univ Basel, Univ Hosp, Dept Radiol, Div Neuroradiol, CH-4003 Basel, Switzerland
[6] Univ Milan, Sci Inst H San Raffaele, Dept Neurosci, I-20122 Milan, Italy
[7] Vall dHebron Univ Hosp, Barcelona, Spain
[8] Royal Melbourne Hosp, Parkville, Vic 3050, Australia
[9] Univ Munster, Dept Neurol, Munster, Germany
[10] Barts & London Queen Marys Sch Med & Dent, Blizard Inst, Neurosci & Trauma Ctr, London, England
[11] Univ Dusseldorf, Dept Neurol, Dusseldorf, Germany
[12] Oxford PharmaGenesis Ltd, Oxford, England
[13] Novartis Pharma AG, Basel, Switzerland
[14] Novartis Pharmaceut, E Hanover, NJ USA
关键词
RELAPSING MULTIPLE-SCLEROSIS; TREATMENT INTERRUPTION; DISEASE-ACTIVITY; ORAL FINGOLIMOD; SAFETY; TRIAL; RISK;
D O I
10.1212/WNL.0000000000001706
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
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 = 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, gadolinium-enhancing 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. Classification of evidence: This study provides Class II evidence that for patients with RRMS switching from natalizumab to fingolimod, shorter natalizumab WO periods are associated with less MRI disease activity than are longer WO periods.
引用
收藏
页码:29 / 39
页数:11
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