Wearing-off symptoms during standard and extended natalizumab dosing intervals: Experiences from the COVID-19 pandemic

Gerd Haga Bringeland,Nello Blaser,Kjell-Morten Myhr,Christian Alexander Vedeler,Sonia Gavasso

doi:10.1016/j.jns.2021.117622

Gerd Haga Bringeland, Nello Blaser + Show 3 more

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https://doi.org/10.1016/j.jns.2021.117622

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Abstract

Natalizumab effectively prevents disease activity in relapsing-remitting multiple sclerosis, but many treated patients report subjective wearing-off symptoms at the end of the 4-week interval between infusions. Extended interval dosing (EID) is a promising strategy to mitigate the risk of natalizumab-associated progressive multifocal leukoencephalopathy, but it is unknown whether EID affects wearing-off symptoms. In this observational study, we evaluated if prevalence or intensity of wearing-off symptoms changed when natalizumab dosing intervals were extended from 4 to 6 weeks in 30 treated patients during the outbreak of COVID-19 in Norway. New or increased wearing-off symptoms during EID were reported by 50%. Symptom increase was more frequent among patients with pre-existing wearing-off symptoms during standard dosing compared to patients without such pre-existing symptoms [p = 0.0005]. Our observations support the need to study the effect of EID on wearing-off symptoms in randomized controlled trials.

Highlights

Natalizumab effectively reduces disease activity in relapsingremitting multiple sclerosis (RRMS) by binding to α4 integrin on the surface of leukocytes, thereby preventing leukocyte migration into the CNS [1]
Accumulating ev idence suggests that extended interval dosing (EID) every 6–8 weeks mitigates the risk of natalizumab-associated progressive multifocal leukoencephalopathy (PML), possibly mediated through receptor occupancy (RO) reduction [7]
Symptom increase during EID was more frequent in patients with pre-existing wearing-off symptoms during standard interval dosing (SID) [p = 0.0005] (Table 1)

Summary

Introduction

Natalizumab effectively reduces disease activity in relapsingremitting multiple sclerosis (RRMS) by binding to α4 integrin on the surface of leukocytes, thereby preventing leukocyte migration into the CNS [1]. Natalizumab is administered intravenously every 4 weeks at standard interval dosing (SID). Many patients report subjective wearingoff symptoms at the end of dosing intervals which improve shortly after infusions [2,3,4]. We have previously proposed that low natalizumab receptor occupancy (RO) may be a contributing cause to such wearingoff symptoms [4]. Accumulating ev idence suggests that extended interval dosing (EID) every 6–8 weeks mitigates the risk of natalizumab-associated progressive multifocal leukoencephalopathy (PML), possibly mediated through RO reduction [7].

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