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

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.