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.</p

Natalizumab remains detectable in patients with multiple sclerosis long after treatment is stopped

Natalizumab is frequently used as a treatment for multiple sclerosis (MS). The occurrence of progressive multifocal leukoencephalopathy (PML) in natalizumab-treated patients indicates that its prominent beneficial effects need to be balanced against the risks. Also, cessation of the drug seems to be associated with recurrence of disease activity. Both the moment of rebound disease activity and the outcome of PML are related to clearance of the drug. Specific features of this IgG4 antibody (i.e. half-antibody exchange) may result in underestimated drug levels. Here, we demonstrate natalizumab levels in 10 patients with relapsing MS, using a recently developed sensitive assay. Remarkably, natalizumab was detectable up to 200 days after cessation of therap