Extended interval dosing of natalizumab in multiple sclerosis

BackgroundNatalizumab (NTZ), a monoclonal antibody to human α4β1/β7 integrin, is an effective therapy for multiple sclerosis (MS), albeit associated with progressive multifocal leukoencephalopathy (PML). Clinicians have been extending the dose of infusions with a hypothesis of reducing PML risk. The...

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Published in:	Journal of neurology, neurosurgery and psychiatry Vol. 87; no. 8; pp. 885 - 889
Main Authors:	Zhovtis Ryerson, L, Frohman, T C, Foley, J, Kister, I, Weinstock-Guttman, B, Tornatore, C, Pandey, K, Donnelly, S, Pawate, S, Bomprezzi, R, Smith, D, Kolb, C, Qureshi, S, Okuda, D, Kalina, J, Rimler, Z, Green, R, Monson, N, Hoyt, T, Bradshaw, M, Fallon, J, Chamot, E, Bucello, M, Beh, S, Cutter, G, Major, E, Herbert, J, Frohman, E M
Format:	Journal Article
Language:	English
Published:	England BMJ Publishing Group LTD 01-08-2016
Subjects:	Adult Body mass index Bone marrow Drug Administration Schedule Female Humans Leukoencephalopathy, Progressive Multifocal - chemically induced Leukoencephalopathy, Progressive Multifocal - prevention & control Magnetic Resonance Imaging Male Middle Aged Multiple sclerosis Multiple Sclerosis - drug therapy Natalizumab - administration & dosage Natalizumab - adverse effects Natalizumab - therapeutic use Neuroimaging Recurrence Retrospective Studies Variables United States > US
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Summary:	BackgroundNatalizumab (NTZ), a monoclonal antibody to human α4β1/β7 integrin, is an effective therapy for multiple sclerosis (MS), albeit associated with progressive multifocal leukoencephalopathy (PML). Clinicians have been extending the dose of infusions with a hypothesis of reducing PML risk. The aim of the study is to evaluate the clinical consequences of reducing NTZ frequency of infusion up to 8 weeks 5 days.MethodsA retrospective chart review in 9 MS centres was performed in order to identify patients treated with extended interval dosing (EID) regimens of NTZ. Patients were stratified into 3 groups based on EID NTZ treatment schedule in individual centres: early extended dosing (EED; n=249) every 4 weeks 3 days to 6 weeks 6 days; late extended dosing (LED; n=274) every 7 weeks to 8 weeks 5 days; variable extended dosing (n=382) alternating between EED and LED. These groups were compared with patients on standard interval dosing (SID; n=1093) every 4 weeks.Results17% of patients on SID had new T2 lesions compared with 14% in EID (p=0.02); 7% of patients had enhancing T1 lesions in SID compared with 9% in EID (p=0.08); annualised relapse rate was 0.14 in the SID group, and 0.09 in the EID group. No evidence of clinical or radiographic disease activity was observed in 62% of SID and 61% of EID patients (p=0.83). No cases of PML were observed in EID group compared with 4 cases in SID cohort.ConclusionsDosing intervals up to 8 weeks 5 days did not diminish effectiveness of NTZ therapy. Further monitoring is ongoing to evaluate if the risk of PML is reduced in patients on EID.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0022-3050 1468-330X
DOI:	10.1136/jnnp-2015-312940