The natalizumab wearing-off effect

Abstract

Objective Natalizumab is effective in treating relapsing-remitting multiple sclerosis (RRMS). However, many patients report an increase of multiple sclerosis symptoms at the end of the natalizumab cycle: a wearing-off effect. The objective of this study was to evaluate the prevalence of the wearing-off effect in patients with standard and extended intervals and to study possible associations with pharmacokinetic/dynamic measurements and patient characteristics in a prospective, monocenter, cross-sectional cohort study. Methods Patients with RRMS, with a minimum of 6 natalizumab infusions, were asked to complete 3 questionnaires: the Multiple Sclerosis Impact Scale, the 36-Item Short Form Health Survey, and a general questionnaire regarding the wearing-off effect. Natalizumab concentration and α4-integrin receptor saturation were measured before redosing. Results Ninety-three patients were included. A total of 54% experienced a wearing-off effect during natalizumab treatment and 32% experienced a current wearing-off effect at time of measurement. The self-reported wearing-off effect was not associated with natalizumab concentration nor with α4-integrin receptor saturation. The wearing-off effect was more frequently reported in the standard interval group (39%) than in the extended interval group (19%); the duration of symptoms was comparable between both groups. The wearing-off effect was not associated with number of infusions, disease duration, age, or sex. Conclusion The wearing-off effect is a frequently reported phenomenon but is unlikely to reflect a nonoptimal pharmacokinetic/dynamic state. We did not find risk factors predicting the wearing-off effect.

The patient-reported wearing-off phenomenon with monoclonal antibody treatments for multiple sclerosis

“…In the previously mentioned Norwegian study, the wearing-off effect was associated with lower α4 integrin receptor occupancy. However, van Kempen et al 12 found that the wearing-off effect was more frequently reported by patients receiving natalizumab every four weeks than in those treated with extended interval dosing. With respect to B-cell depletion, patients whose rituximab treatment is interrupted or stopped still show prolonged disease suppression, even when alternative DMT is not started.…”

Can Natalizumab be Safely Used After Ocrelizumab in Treating Multiple Sclerosis?

“…Patients may also experience infusion reactions (although more likely to occur during initial infusion) [7] or develop an intolerance to preinfusion medications use. Finally, patients may request a return to NTZ having seen a decline in a sense of "the feel-good effect" described with the drug [8], which has previously been described as a main reason for switching back to NTZ [9].…”