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An observational study of alemtuzumab following fingolimod for multiple sclerosis

Willis, Mark, Pearson, Owen, Illes, Zsolt, Sejbaek, Tobias, Nielson, Christian, Duddy, Martin, Petheram, Kate, van Munster, Casper, Killestein, Joep, Malmestrom, Clas, Tallantyre, Emma and Robertson, Neil 2017. An observational study of alemtuzumab following fingolimod for multiple sclerosis. Neuroimmunology and Neuroinflammation 4 (2) , E320. 10.​1212/​NXI.​0000000000000320

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Abstract

Objective: To describe a series of patients with relapsing multiple sclerosis (MS) who experienced significant and unexpected disease activity within the first 12 months after switching from fingolimod to alemtuzumab. Methods: Patients with relapsing MS treated sequentially with fingolimod then alemtuzumab who experienced significant subsequent disease activity were identified by personal communication with 6 different European neuroscience centres. Results: Nine patients were identified. Median disease duration to alemtuzumab treatment was 94 (39-215) months and follow-up from time of first alemtuzumab cycle 20 (14-21) months. Following first alemtuzumab infusion cycle 8 patients were identified by at least 1 clinical relapse and radiological disease activity and one by significant radiological disease activity alone. Conclusions: We acknowledge the potential for ascertainment bias; however, these cases may illustrate an important cause of reduced efficacy of alemtuzumab in a vulnerable group of MS patients most in need of disease control. We suggest that significant and unexpected subsequent disease activity after alemtuzumab induction results from prolonged sequestration of auto-reactive lymphocytes following fingolimod withdrawal, allowing these cells to be concealed from the usual biological effect of alemtuzumab. Subsequent lymphocyte egress then provokes disease reactivation. Further animal studies and clinical trials are required to confirm these phenomena and in the meantime careful consideration should be given to mode of action of individual therapies and sequential treatment effects in MS when designing personalised treatment regimes.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Subjects: R Medicine > R Medicine (General)
Publisher: OAE Publishing
ISSN: 2347-8659
Date of First Compliant Deposit: 14 December 2016
Date of Acceptance: 5 December 2016
Last Modified: 28 Nov 2017 21:31
URI: http://orca-mwe.cf.ac.uk/id/eprint/96901

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