Extended interval dosing of natalizumab in multiple sclerosis

L. Zhovtis Ryerson, T. C. Frohman, J. Foley, I. Kister, B. Weinstock-Guttman, C. Tornatore, K. Pandey, S. Donnelly, S. Pawate, R. Bomprezzi, D. Smith, C. Kolb, S. Qureshi, Darin Okuda, J. Kalina, Z. Rimler, R. Green, Nancy L Monson, T. Hoyt, M. BradshawJ. Fallon, E. Chamot, M. Bucello, Shin C Beh, G. Cutter, E. Major, J. Herbert, Elliot Frohman

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96 Scopus citations


Background: Natalizumab (NTZ), a monoclonal antibody to human α4 β17 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. Methods: A 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. Results: 17% 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. Conclusions: Dosing 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.

Original languageEnglish (US)
Pages (from-to)885-889
Number of pages5
JournalJournal of Neurology, Neurosurgery and psychiatry
Issue number8
StatePublished - Jan 8 2016

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology
  • Psychiatry and Mental health


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