An observational study of alemtuzumab following fingolimod for multiple sclerosis

Mark Willis, Owen Pearson, Zsolt Illes, Tobias Sejbaek, Christian Nielsen, Martin Duddy, Kate Petheram, Caspar van Munster, Joep Killestein, Clas Malmeström, Emma Tallantyre, Neil Robertson

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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 centers.

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 radiologic disease activity and 1 by significant radiologic 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 patients with MS most in need of disease control. We suggest that significant and unexpected subsequent disease activity after alemtuzumab induction results from prolonged sequestration of autoreactive 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 personalized treatment regimens.

Original languageEnglish
Article numbere320
JournalNeurology: Neuroimmunology & Neuroinflammation
Volume4
Issue number2
Number of pages7
ISSN2332-7812
DOIs
Publication statusPublished - 2017

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Willis, Mark ; Pearson, Owen ; Illes, Zsolt ; Sejbaek, Tobias ; Nielsen, Christian ; Duddy, Martin ; Petheram, Kate ; van Munster, Caspar ; Killestein, Joep ; Malmeström, Clas ; Tallantyre, Emma ; Robertson, Neil. / An observational study of alemtuzumab following fingolimod for multiple sclerosis. In: Neurology: Neuroimmunology & Neuroinflammation. 2017 ; Vol. 4, No. 2.
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title = "An observational study of alemtuzumab following fingolimod for multiple sclerosis",
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 centers.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 radiologic disease activity and 1 by significant radiologic 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 patients with MS most in need of disease control. We suggest that significant and unexpected subsequent disease activity after alemtuzumab induction results from prolonged sequestration of autoreactive 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 personalized treatment regimens.",
author = "Mark Willis and Owen Pearson and Zsolt Illes and Tobias Sejbaek and Christian Nielsen and Martin Duddy and Kate Petheram and {van Munster}, Caspar and Joep Killestein and Clas Malmestr{\"o}m and Emma Tallantyre and Neil Robertson",
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Willis, M, Pearson, O, Illes, Z, Sejbaek, T, Nielsen, C, Duddy, M, Petheram, K, van Munster, C, Killestein, J, Malmeström, C, Tallantyre, E & Robertson, N 2017, 'An observational study of alemtuzumab following fingolimod for multiple sclerosis', Neurology: Neuroimmunology & Neuroinflammation, vol. 4, no. 2, e320. https://doi.org/10.1212/NXI.0000000000000320

An observational study of alemtuzumab following fingolimod for multiple sclerosis. / Willis, Mark; Pearson, Owen; Illes, Zsolt; Sejbaek, Tobias; Nielsen, Christian; Duddy, Martin; Petheram, Kate; van Munster, Caspar; Killestein, Joep; Malmeström, Clas; Tallantyre, Emma; Robertson, Neil.

In: Neurology: Neuroimmunology & Neuroinflammation, Vol. 4, No. 2, e320, 2017.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - An observational study of alemtuzumab following fingolimod for multiple sclerosis

AU - Willis, Mark

AU - Pearson, Owen

AU - Illes, Zsolt

AU - Sejbaek, Tobias

AU - Nielsen, Christian

AU - Duddy, Martin

AU - Petheram, Kate

AU - van Munster, Caspar

AU - Killestein, Joep

AU - Malmeström, Clas

AU - Tallantyre, Emma

AU - Robertson, Neil

PY - 2017

Y1 - 2017

N2 - 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 centers.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 radiologic disease activity and 1 by significant radiologic 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 patients with MS most in need of disease control. We suggest that significant and unexpected subsequent disease activity after alemtuzumab induction results from prolonged sequestration of autoreactive 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 personalized treatment regimens.

AB - 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 centers.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 radiologic disease activity and 1 by significant radiologic 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 patients with MS most in need of disease control. We suggest that significant and unexpected subsequent disease activity after alemtuzumab induction results from prolonged sequestration of autoreactive 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 personalized treatment regimens.

U2 - 10.1212/NXI.0000000000000320

DO - 10.1212/NXI.0000000000000320

M3 - Journal article

C2 - 28101520

VL - 4

JO - Neurology: Neuroimmunology & Neuroinflammation

JF - Neurology: Neuroimmunology & Neuroinflammation

SN - 2332-7812

IS - 2

M1 - e320

ER -