Background: It is unclear whether natalizumab and fingolimod have analogous efficacy for relapsing-remitting multiple sclerosis (RRMS). Objective: To compare the outcome of RRMS patients treated with either therapy. Methods: RRMS patients treated with natalizumab or fingolimod at Verona Hospital, Italy, were included. The study design was retrospective, based on prospectively collected clinical and MRI data. As efficacy outcomes, time to relapse, relapse rate, expanded disability status scale (EDSS) score change, and new T2/gadolinium-enhancing lesions on brain MRI were compared over treatment period between the two groups. Multivariate Cox and logistic regression models were used to control for potential confounders. Results: Fifty-seven subjects receiving natalizumab and 30 receiving fingolimod for a median duration of 23 (1-63) and 22 (2-35) months, respectively (p = 0.22) were included. Patients treated with natalizumab had a more active pre-treatment disease course compared to those treated with fingolimod. In multivariate analysis, the relapse risk was reduced in patients on natalizumab (Hazard Ratio = 0.33; 95% CI = 0.11-1.03; p = 0.056) compared to those on fingolimod. There was no significant difference in EDSS and MRI outcomes. No relevant unexpected adverse events occurred. One patient discontinued natalizumab for progressive multifocal leukoencephalopathy. Conclusions: RRMS patients receiving natalizumab had higher baseline disease activity and lower relapse risk over 20 months of treatment compared to those receiving fingolimod. Head-to-head randomized clinical trials are needed.

Keywords:
Multiple sclerosis, Natalizumab, Fingolimod
1.
Rudick RA, Stuart WH, Calabresi PA, et al: Natalizumab plus interferon beta-1a for relapsing multiple sclerosis. N Engl J Med 2006;354:911-923.
2.
Cohen JA, Barkhof F, Comi G, et al: Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. N Engl J Med 2010;362:402-415.
3.
Polman CH, Reingold SC, Edan G, et al: Diagnostic criteria for multiple sclerosis: 2005 revisions to the ‘McDonald Criteria'. Ann Neurol 2005;58:840-846.
4.
Lublin FD, Reingold SC: Defining the clinical course of multiple sclerosis: results of an international survey. National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis. Neurology 1996;46:907-911.
5.
Comi G, Kappos L, Palace J, et al: Cardiac safety of fingolimod 0.5 mg during the first dose observation in 4-month, open-label, multi-center FIRST study in patients with relapsing MS. Neurology 2012;78:S41.003.
6.
Kurtzke JF: Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 1983;33:1444-1452.
7.
McDonald WI, Compston A, Edan G, et al: Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol 2001;50:121-127.
8.
Tubridy N, Behan PO, Capildeo R, et al: The effect of anti-alpha4 integrin antibody on brain lesion activity in MS. The UK Antegren Study Group. Neurology 1999;53:466-472.
9.
Miller DH, Khan OA, Sheremata WA, et al: A controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 2003;348:15-23.
10.
Polman CH, O'Connor PW, Havrdova E, et al: A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 2006;354:899-910.
11.
Rudick RA, Stuart WH, Calabresi PA, et al: Natalizumab plus interferon beta-1a for relapsing multiple sclerosis. N Engl J Med 2006;354:911-923.
12.
Bloomgren G, Richman S, Hotermans C, et al: Risk of natalizumab-associated progressive multifocal leukoencephalopathy. N Engl J Med 2012;366:1870-1880.
14.
Kappos L, Radue EW, O'Connor P, et al: A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. N Engl J Med 2010;362:387-401.
15.
Cohen JA, Barkhof F, Comi G, et al: Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. N Engl J Med 2010;362:402-415.
16.
Centonze D, Rossi S, Rinaldi F, Gallo P: Severe relapses under fingolimod treatment prescribed after natalizumab. Neurology 2012;79:2004-2005.
17.
Rinaldi F, Seppi D, Calabrese M, Perini P, Gallo P: Switching therapy from natalizumab to fingolimod in relapsing-remitting multiple sclerosis: clinical and magnetic resonance imaging findings. Mult Scler 2012;18:1640-1643.
18.
Daelman L, Maitrot A, Maarouf A, Chaunu MP, Papeix C, Tourbah A: Severe multiple sclerosis reactivation under fingolimod 3 months after natalizumab withdrawal. Mult Scler 2012;18:1647-1649.
19.
Jander S, Turowski B, Kieseier BC, Hartung HP: Emerging tumefactive multiple sclerosis after switching therapy from natalizumab to fingolimod. Mult Scler 2012;18:1650-1652.
20.
Sempere AP, Martín-Medina P, Berenguer-Ruiz L, et al: Switching from natalizumab to fingolimod: an observational study. Acta Neurol Scand 2013;128:e6-e10.
21.
Laroni A, Brogi D, Milesi V, Abate L, Uccelli A, Mancardi G: Early switch to fingolimod may decrease the risk of disease recurrence after natalizumab interruption. Mult Scler 2012;19:1236-1237.
22.
Havla J, Tackenberg B, Hellwig K, et al: Fingolimod reduces recurrence of disease activity after natalizumab withdrawal in multiple sclerosis. J Neurol 2013;260:1382-1387.
23.
de Seze J, Ongagna JC, Collongues N, et al: Reduction of the washout time between natalizumab and fingolimod. Mult Scler 2013; 19:1248.
24.
O'Day K, Meyer K, Miller RM, Agarwal S, Franklin M: Cost-effectiveness of natalizumab versus fingolimod for the treatment of relapsing multiple sclerosis. J Med Econ 2011;14:617-627.
25.
Del Santo F, Maratea D, Fadda V, Trippoli S, Messori A: Treatments for relapsing-remitting multiple sclerosis: summarising current information by network meta-analysis. Eur J Clin Pharmacol 2012;68:441-448.
26.
Braune S, Lang M, Bergmann A; NTC Study Group: Second line use of Fingolimod is as effective as Natalizumab in a German out-patient RRMS-cohort. J Neurol 2013;260:2981-2985, Epub ahead of print.
© 2014 S. Karger AG, Basel
2014
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.