Fingolimod reduces recurrence of disease activity after natalizumab withdrawal in multiple sclerosis
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After discontinuation of natalizumab (NAT), multiple sclerosis (MS) disease activity often recurs. We assessed the recurrence of clinical disease activity during the first year after switching from NAT to fingolimod (FTY) in patients with relapsing-remitting MS. The number of relapses and the annualized relapse rate (ARR) before, during and after NAT discontinuation were determined and compared between 26 MS patients who switched to FTY within 24 weeks, and 10 MS patients who remained without disease modifying therapy (therapy free group = TFG). Median follow-up post-NAT discontinuation was 55.1 weeks. In a subgroup (n = 20), the occurrence of contrast-enhancing-lesions (Gd+) on magnetic resonance imaging (MRI) was determined. Eleven patients (42 %) in the FTY group and seven patients (70 %) in the TFG had one or more relapses after cessation of NAT during follow-up (p < 0.05). One of the 11 (9 %) patients in the FTY group and 6/9 (67 %) patients in the TFG showed Gd+ lesions during follow-up (p < 0.05). Patients who switched to FTY ≤ 12 weeks after NAT discontinuation (n = 9) showed a trend for a lower post-NAT ARR compared to patients who started FTY therapy >12 weeks after NAT was stopped (n = 17). Most relapses in the FTY group occurred just before or within 8 weeks after starting FTY. Our observation suggests that initiation of FTY treatment after NAT discontinuation reduces the recurrence of disease activity compared to withdrawal without further immunomodulatory treatment. In the FTY group the ARR tended to depend on the time interval between discontinuation of NAT and initiation of FTY.
KeywordsMultiple sclerosis Natalizumab discontinuation Fingolimod Disease activity
The authors thank Dr. E. Schuh and Prof. E. Meinl for helpful comments on the manuscript.
Retrospective data analysis is approved by the local ethics committee and has therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.
Conflicts of interests
Dr. Havla received speaker honoraria, travel expenses and personal compensations from Merck-Serono, Teva Pharma, Bayer Healthcare, Novartis Pharma and Biogen-Idec. Dr. Tackenberg received travel reimbursements, speaker and consulting honoraria from Bayer Healthcare, Biogen Idec, Merck Serono, Novartis Pharma, and Teva Pharma as well as research support from Bayer Healthcare, Biogen-Idec and Novartis Pharma. Dr. Hellwig reports research support from Biogen Idec, Bayer Healthcare, Merck Serono, Sanofi-Aventis and Novartis Pharma as well as speaker honoraria from Biogen Idec, Bayer Healthcare, Merck-Serono, Sanofi-Aventis and Novartis Pharma. Dr. Meinl received travel expenses from Bayer. Dr. Krumbholz has received grant support by Novartis Pharma. Dr. Seitz and Dr. Eienbröker have nothing to disclose. Dr. Gold received speakers and consulting honoraria, scientific grant support from Bayer Healthcare, Biogen-Idec, Merck-Serono, Novartis Pharma and Teva Pharma. Dr. Hohlfeld is supported by the Deutsche Forschungsgemeinschaft (SFB/TR 128) and by the Bundesministerium für Bildung und Forschung (BMBFKKNMS) and has received personal compensations from Bayer Healthcare, Teva Pharma, Merck-Serono, Biogen-Idec and Novartis Pharma. Dr. Kleiter reports receiving travel reimbursements and speaker and consulting honoraria from Bayer Healthcare, Biogen-Idec, Merck Serono, and Novartis as well as research support from Bayer Healthcare, Novartis Pharma and Biogen-Idec. Dr. Kümpfel has received travel expenses and personal compensations from Bayer Healthcare, Teva Pharma, Merck-Serono, Novartis, Sanofi-Aventis and Biogen-Idec as well as grant support from Bayer-Schering AG.
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