Extended interval dosing of natalizumab in multiple sclerosis

  • 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
Journal of Neurology, Neurosurgery, & Psychiatry 87(8):p 885-889, August 2016. | DOI: 10.1136/jnnp-2015-312940

Background

Natalizumab (NTZ), a monoclonal antibody to human α4β17 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.

Copyright © 2016 BMJ Publishing Group Ltd