PT  - JOURNAL ARTICLE
AU  - L Zhovtis Ryerson
AU  - T C Frohman
AU  - J Foley
AU  - I Kister
AU  - B Weinstock-Guttman
AU  - C Tornatore
AU  - K Pandey
AU  - S Donnelly
AU  - S Pawate
AU  - R Bomprezzi
AU  - D Smith
AU  - C Kolb
AU  - S Qureshi
AU  - D Okuda
AU  - J Kalina
AU  - Z Rimler
AU  - R Green
AU  - N Monson
AU  - T Hoyt
AU  - M Bradshaw
AU  - J Fallon
AU  - E Chamot
AU  - M Bucello
AU  - S Beh
AU  - G Cutter
AU  - E Major
AU  - J Herbert
AU  - E M Frohman
TI  - Extended interval dosing of natalizumab in multiple sclerosis
AID  - 10.1136/jnnp-2015-312940
DP  - 2016 Aug 01
TA  - Journal of Neurology, Neurosurgery & Psychiatry
PG  - 885--889
VI  - 87
IP  - 8
4099  - http://jnnp.bmj.com/content/87/8/885.short
4100  - http://jnnp.bmj.com/content/87/8/885.full
SO  - J Neurol Neurosurg Psychiatry2016 Aug 01; 87
AB  - Background Natalizumab (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.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.