Influence of personalized extended interval dosing on the natalizumab wearing-off effect - a sub-study of the NEXT-MS trial

J Neurol Sci. 2024 Jul 15:462:123102. doi: 10.1016/j.jns.2024.123102. Epub 2024 Jun 22.

Abstract

Background and objectives: Wearing-off symptoms during natalizumab treatment in multiple sclerosis are characterized by an increase of MS-related symptoms prior to natalizumab administration. The influence of extended interval dosing (EID) on wearing-off symptoms are important to consider, as this might cause hesitancy in initiating or continuing EID.

Methods: Participants of the NEXT-MS trial, in which treatment intervals are adjusted based on drug concentrations, were divided into two groups: an extended group containing participants with at least one week of additional interval extension, and a group with a fixed interval during the trial (range 4-7 weeks). Changes in the occurrence, frequency, onset, and severity of wearing-off symptoms were evaluated.

Results: 255 participants were included (extended group n = 171, fixed group n = 84). The odds on occurrence of wearing-off symptoms in the extended group did not increase after extending the treatment interval. Additional analyses for frequency, onset, and severity of wearing-off symptoms showed no changes over time. Mean decrease in natalizumab drug concentration did not influence the frequency of wearing-off symptoms.

Discussion: Wearing-off symptoms were not reinforced by further extending the natalizumab interval. Wearing-off symptoms might increase in a minority of patients after EID, although our data support the view that wearing-off symptoms appear to be unrelated to the decrease in natalizumab trough drug concentrations.

Keywords: Extended interval dosing; Multiple sclerosis; Natalizumab; Wearing-off.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Drug Administration Schedule
  • Female
  • Humans
  • Immunologic Factors* / administration & dosage
  • Male
  • Middle Aged
  • Multiple Sclerosis / drug therapy
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy
  • Natalizumab* / administration & dosage
  • Natalizumab* / therapeutic use
  • Treatment Outcome

Substances

  • Natalizumab
  • Immunologic Factors