Toorop, Alyssa A;
van Lierop, Zoë Ygj;
Gelissen, Liza My;
Hoitsma, Elske;
Zeinstra, Esther Mpe;
van Rooij, Luuk C;
van Munster, Caspar Ep;
... van Kempen, Zoé LE; + view all
(2023)
Prospective trial of natalizumab personalised extended interval dosing by therapeutic drug monitoring in relapsing-remitting multiple sclerosis (NEXT-MS).
Journal of Neurology, Neurosurgery and Psychiatry (JNNP)
10.1136/jnnp-2023-332119.
(In press).
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Abstract
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.
| Type: | Article |
|---|---|
| Title: | Prospective trial of natalizumab personalised extended interval dosing by therapeutic drug monitoring in relapsing-remitting multiple sclerosis (NEXT-MS) |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1136/jnnp-2023-332119 |
| Publisher version: | https://doi.org/10.1136/jnnp-2023-332119 |
| Language: | English |
| Additional information: | This version is the author-accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Multiple Sclerosis, Natalizumab, Extended Interval Dosing, Therapeutic Drug Monitoring, Neurofilament Light. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Brain Repair and Rehabilitation |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10183554 |
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