Zoé L E van Kempen1, Djoeke Doesburg2, Iris Dekker2, Birgit I Lissenberg-Witte2, Annick de Vries2, Iris A Claessen2, Anja Ten Brinke2, Theo Rispens2, Joep Killestein2. 1. From the Amsterdam UMC (Z.L.E.v.K., D.D., I.D., B.I.L.-W., J.K.), Vrije Universiteit Amsterdam; Departments of Neurology (Z.L.E.v.K., D.D., I.D., J.K.) and Radiology & Nuclear Medicine (I.D.), MS Center Amsterdam, Amsterdam Neuroscience; and Departments of Epidemiology and Biostatistics (B.I.L.-W.) and Immunology (A.d.V., I.A.C., A.t.B., T.R.), Landsteiner Laboratory Sanquin Research, Amsterdam, the Netherlands. z.vankempen@amsterdamumc.nl. 2. From the Amsterdam UMC (Z.L.E.v.K., D.D., I.D., B.I.L.-W., J.K.), Vrije Universiteit Amsterdam; Departments of Neurology (Z.L.E.v.K., D.D., I.D., J.K.) and Radiology & Nuclear Medicine (I.D.), MS Center Amsterdam, Amsterdam Neuroscience; and Departments of Epidemiology and Biostatistics (B.I.L.-W.) and Immunology (A.d.V., I.A.C., A.t.B., T.R.), Landsteiner Laboratory Sanquin Research, Amsterdam, the Netherlands.
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.
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.
Authors: Carrie M Hersh; Bernd Kieseier; Carl de Moor; Deborah M Miller; Denise Campagnolo; James R Williams; Kathryn C Fitzgerald; Kuangnan Xiong; Marisa P McGinley; Megan Hyland; Richard A Rudick; Tjalf Ziemssen; Irene Koulinska Journal: Mult Scler J Exp Transl Clin Date: 2021-04-15