TY - JOUR
T1 - Prospective trial of natalizumab personalised extended interval dosing by therapeutic drug monitoring in relapsing-remitting multiple sclerosis (NEXT-MS)
AU - Toorop, Alyssa A
AU - van Lierop, Zoë Ygj
AU - Gelissen, Liza My
AU - Hoitsma, Elske
AU - Zeinstra, Esther Mpe
AU - van Rooij, Luuk C
AU - van Munster, Caspar Ep
AU - Vennegoor, Anke
AU - Mostert, Jop P
AU - Wokke, Beatrijs Ha
AU - Kalkers, Nynke F
AU - Hoogervorst, Erwin Lj
AU - van Eijk, Jeroen Jj
AU - Roosendaal, Christiaan M
AU - Kragt, Jolijn J
AU - Eurelings, Marijke
AU - van Genugten, Jessie
AU - Nielsen, Jessica
AU - Sinnige, Lgf
AU - Kloosterziel, Mark E
AU - Arnoldus, Edo Pj
AU - van Dijk, Gert W
AU - Bouvy, Willem H
AU - Wessels, Mark Hj
AU - Boonkamp, Lynn
AU - Strijbis, Eva Mm
AU - van Oosten, Bob W
AU - De Jong, Brigit A
AU - Lissenberg-Witte, Birgit I
AU - Barkhof, Frederik
AU - Moraal, Bastiaan
AU - Teunissen, Charlotte E
AU - Rispens, Theo
AU - Uitdehaag, Bernard Mj
AU - Killestein, Joep
AU - van Kempen, Zoé LE
N1 - Funding Information: This study was kindly funded by the Dutch MS Research Foundation (18-1030), the Brain Foundation Netherlands (HA2015.01.05), and Innovation Fund Healthcare insurers (B 18-313/ File 3.798). Publisher Copyright: © Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.
PY - 2023/11/14
Y1 - 2023/11/14
N2 - BACKGROUND: Extended interval dosing (EID) of natalizumab is a promising strategy to optimise treatment in multiple sclerosis (MS). Personalised EID by therapeutic drug monitoring can enable further extension of treatment intervals.METHODS: The NEXT-MS trial is an investigator-initiated prospective phase IV non-randomised study. Adults with a diagnosis of relapsing-remitting MS who received ≥6 natalizumab infusions were included in three groups: personalised EID with a target drug trough concentration of 10 µg/mL (EID10), an exploratory group of personalised EID with a target of 5 µg/mL (EID5) and standard interval dosing (SID) of 4 weeks. The primary outcome is radiological disease activity (new/newly enlarged T2 lesions) comparing the EID10 group to a historical cohort of SID (HSID).RESULTS: Results of the first phase of the NEXT-MS trial are reported here (n=376) as the study will continue with an amended protocol. In the EID10 group (n=251), incidence rate of radiological activity was 10.0 per 1000 person-years, which was non-inferior to the HSID cohort (24.7 per 1000 person-years (n=87), incidence rate difference 14.7, 90% CI -4.5 to 34.0). Incidence rate of radiological activity was 10.0 per 1000 person-years in the EID5 group (n=65), and 47.0 per 1000 person-years in the SID group (n=60). Serum neurofilament light levels did not increase over time within the EID groups. There were no cases of progressive multifocal leukoencephalopathy.CONCLUSIONS: MS disease activity is adequately controlled with personalised natalizumab EID. Interval extension to a drug trough concentration of 5 µg/mL is likely a safe target to extend natalizumab treatment intervals >6 weeks.TRIAL REGISTRATION NUMBER: NCT04225312.
AB - BACKGROUND: Extended interval dosing (EID) of natalizumab is a promising strategy to optimise treatment in multiple sclerosis (MS). Personalised EID by therapeutic drug monitoring can enable further extension of treatment intervals.METHODS: The NEXT-MS trial is an investigator-initiated prospective phase IV non-randomised study. Adults with a diagnosis of relapsing-remitting MS who received ≥6 natalizumab infusions were included in three groups: personalised EID with a target drug trough concentration of 10 µg/mL (EID10), an exploratory group of personalised EID with a target of 5 µg/mL (EID5) and standard interval dosing (SID) of 4 weeks. The primary outcome is radiological disease activity (new/newly enlarged T2 lesions) comparing the EID10 group to a historical cohort of SID (HSID).RESULTS: Results of the first phase of the NEXT-MS trial are reported here (n=376) as the study will continue with an amended protocol. In the EID10 group (n=251), incidence rate of radiological activity was 10.0 per 1000 person-years, which was non-inferior to the HSID cohort (24.7 per 1000 person-years (n=87), incidence rate difference 14.7, 90% CI -4.5 to 34.0). Incidence rate of radiological activity was 10.0 per 1000 person-years in the EID5 group (n=65), and 47.0 per 1000 person-years in the SID group (n=60). Serum neurofilament light levels did not increase over time within the EID groups. There were no cases of progressive multifocal leukoencephalopathy.CONCLUSIONS: MS disease activity is adequately controlled with personalised natalizumab EID. Interval extension to a drug trough concentration of 5 µg/mL is likely a safe target to extend natalizumab treatment intervals >6 weeks.TRIAL REGISTRATION NUMBER: NCT04225312.
KW - multiple sclerosis
UR - http://www.scopus.com/inward/record.url?scp=85177497494&partnerID=8YFLogxK
U2 - https://doi.org/10.1136/jnnp-2023-332119
DO - https://doi.org/10.1136/jnnp-2023-332119
M3 - Article
C2 - 37963723
SN - 0022-3050
JO - Journal of neurology, neurosurgery, and psychiatry
JF - Journal of neurology, neurosurgery, and psychiatry
ER -