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.
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Improvement of fatigue, depression, and processing speed two weeks post Natalizumab infusion in Multiple Sclerosis: No difference between standard and extended interval dosing schedules.
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IRCCS Neuromedicine, Pozzilli, IS 86077, Italy; Department of Human Neurosciences, Sapienza University of Rome, Rome 00185, Italy. Electronic address:
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Neurochemistry Laboratory, Department of Laboratory Medicine, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam, The Netherlands.
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Insight into motor fatigue mechanisms in natalizumab treated multiple sclerosis patients with wearing off.
Sci Rep
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IRCCS Neuromed, 86077, Pozzilli, IS, Italy.
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View Article and Find Full Text PDFInfluence of personalized extended interval dosing on the natalizumab wearing-off effect - a sub-study of the NEXT-MS trial.
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MS Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC location VUmc, Amsterdam, the Netherlands. Electronic address:
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.
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