@article{ca67f32e7817457ab6258fced6422875,
title = "Extended interval dosing of natalizumab in multiple sclerosis",
abstract = "Background: Natalizumab (NTZ), a monoclonal antibody to human α4 β1/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. 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.",
author = "{Zhovtis Ryerson}, L. and Frohman, {T. C.} and J. Foley and I. Kister and B. Weinstock-Guttman and C. Tornatore and K. Pandey and S. Donnelly and S. Pawate and R. Bomprezzi and D. Smith and C. Kolb and S. Qureshi and Darin Okuda and J. Kalina and Z. Rimler and R. Green and Monson, {Nancy L} and T. Hoyt and M. Bradshaw and J. Fallon and E. Chamot and M. Bucello and Beh, {Shin C} and G. Cutter and E. Major and J. Herbert and Elliot Frohman",
note = "Funding Information: Competing interests LZR has received research support from Biogen Idec. She has received compensation for advisory board and speaker activities from Biogen Idec and Teva. TCF has received speaker and consultant fees from Novartis, Genzyme and Acorda. IK is the member of scientific advisory board for Biogen Idec and received research support from Guthy-Jackson Charitable Foundation, National Multiple Sclerosis Society, Biogen-Idec, Serono and Navartis. JF has served as a consultant for and receives honoraria from Biogen, Genzyme, Teva, Novartis and Avanir. BW-G has participated in speaker's bureaus and served as a consultant for Biogen Idec, Teva Neuroscience, EMD Serono, Novartis, Genzyme & Sanofi, Acorda Therapeutics, Inc and Genentech. BW-G also has received grant/research support from the agencies listed in the previous sentence as well as Questcor Pharmaceuticals, Inc and Shire. She serves in the editorial board for BMJ Neurology, Journal of International MS and CNS Drugs. CT has received speaker and consulting fees from Biogen Idec. KP has received speaker and consulting fees from Acorda, TEVA and Biogen. DS has received speaker and consulting fees from Biogen Idec. CK has received speaker and consulting fees from Biogen, Teva, EMD Serono and Acorda. DO received lecture fees from Acorda Therapeutics, Genzyme and TEVA Neuroscience, consulting and advisory board fees from Genzyme, Novartis and TEVA Neuroscience, and research support from Biogen. EC reports grants from Genzyme Corp, grants from Consortium of Multiple Sclerosis Centers, grants from Biogen Idec, grants from National Multiple Sclerosis Society, outside the submitted work. MBu has received speaker and consulting fees from Genzyme, Teva and EMD Serono. GC has received consulting, speaking fees and advisory boards: Cerespir Inc, Consortium of MS Centers (grant), D3 (Drug Discovery and Development), Genzyme, Genentech, Innate Therapeutics, Jannsen Pharmaceuticals, Klein-Buendel Incorporated, Medimmune, Novartis, Opexa Therapeutics, Receptos, Roche, Savara Inc, Spiniflex Pharmaceuticals, Somahlution, Teva pharmaceuticals, Transparency Life Sciences. EM reports personal fees from PML Consortium, personal fees from Takeda/Millennium Pharma, personal fees from Glaxo Smith Klein, personal fees from Genentech Roche, personal fees from Sanofi Genzyme, outside the submitted work. JH has received research support from Biogen Idec. EMF has received speaker and consultant fees from Novartis, Genzyme, TEVA and Acorda. Publisher Copyright: {\textcopyright} 2016 Published by the BMJ Publishing Group Limited.",
year = "2016",
month = jan,
day = "8",
doi = "10.1136/jnnp-2015-312940",
language = "English (US)",
volume = "87",
pages = "885--889",
journal = "Journal of Neurology, Neurosurgery and psychiatry",
issn = "0022-3050",
publisher = "BMJ Publishing Group",
number = "8",
}