The natalizumab wearing-off effect: End of natalizumab cycle, recurrence of MS symptoms

Zoé L E van Kempen, Djoeke Doesburg, Iris Dekker, Birgit I Lissenberg-Witte, Annick de Vries, Iris A Claessen, Anja Ten Brinke, Theo Rispens, Joep Killestein

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)e1579-e1586
JournalNeurology
Volume93
Issue number17
DOIs
Publication statusPublished - 22 Oct 2019

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