RT Journal Article
SR Electronic
T1 An observational study of alemtuzumab following fingolimod for multiple sclerosis
JF Neurology - Neuroimmunology Neuroinflammation
JO Neurol Neuroimmunol Neuroinflamm
FD Lippincott Williams & Wilkins
SP e320
DO 10.1212/NXI.0000000000000320
VO 4
IS 2
A1 Mark Willis
A1 Owen Pearson
A1 Zsolt Illes
A1 Tobias Sejbaek
A1 Christian Nielsen
A1 Martin Duddy
A1 Kate Petheram
A1 Caspar van Munster
A1 Joep Killestein
A1 Clas Malmeström
A1 Emma Tallantyre
A1 Neil Robertson
YR 2017
UL http://nn.neurology.org/content/4/2/e320.abstract
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.ARR=annualized relapse rate; DMT=disease-modifying treatment; IFN=interferon; MS=multiple sclerosis; Treg=regulatory CD4+ T cell