The natalizumab wearing-off effect: End of natalizumab cycle, recurrence of MS symptoms. (22nd October 2019)

• Record Type: Journal Article
• Authors: van Kempen, Zoé L.E.; Doesburg, Djoeke; Dekker, Iris; Lissenberg-Witte, Birgit I.; de Vries, Annick; Claessen, Iris A.; Brinke, Anja ten; Rispens, Theo; Killestein, Joep
• Is Part Of: Neurology. Volume 93:Number 17(2019)
• Publication Date: 2019-10-22
• Subjects: Neurology -- Periodicals; Neurology -- Periodicals; Neurologie -- Périodiques; 616.8
• DOI: 10.1212/WNL.0000000000008357
• Languages: English
• ISSNs: 0028-3878

Abstract

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.