Author Of 1 Presentation
P0223 - “Personalized extended interval dosing of natalizumab in relapsing remitting multiple sclerosis – a prospective multicenter trial in The Netherlands" (ID 1418)
Abstract
Background
Natalizumab is an effective disease-modifying therapy for relapsing remitting multiple sclerosis (RRMS). However, natalizumab trough concentrations remain high in a treatment regimen of 4-weekly infusions in 85% of patients. Previous studies showed that patients on extended interval dosing (EID) of natalizumab had comparable disease activity to standard interval dosing (SID) and a decreased risk of progressive multifocal leukoencephalopathy.
Objectives
To validate the maintenance of efficacy, measured by radiological disease activity, of personalized EID of natalizumab based on natalizumab trough concentrations. Feasibility of further extending intervals up to trough concentration of 5 μg/ml will be studied in a subgroup.
Methods
In this national multicenter prospective study (ClinicalTrials.gov Identifier: NCT04225312), 300 patients diagnosed with RRMS that received ≥ 6 consecutive natalizumab infusions will be included. Patients will be included in the main personalized EID group (aimed trough concentration 10 μg/ml), the low EID group (trough 5 μg/ml) or the SID group. Follow-up is two years with an extension phase of two years with annual MRI brain scans and 6 monthly scans for patients in the low EID group. Questionnaires will be filled in yearly by all participants.
Results
Inclusion of patients started in February 2020. Participants will be included in 22 centers in The Netherlands. So far, 69 patients were included, of whom 19 in the main EID group, showing natalizumab trough concentrations at baseline of 18.5 μg/ml (IQR 9.2 to 30.0). Current treatment intervals are 4 weeks (n=5), 5 weeks (n=5), 6 weeks (n=8) or 7 weeks (n=1). In the low EID group (n=37), natalizumab trough concentrations at baseline were 15.0 μg/ml (IQR 10.3 to 21.8). Current treatment intervals are 4 weeks (n=2), 5 weeks (n=8), 6 weeks (n=17) or 7 weeks (n=10). In the SID group (n=13), natalizumab trough concentrations at baseline were 18.0 μg/ml (IQR 14.5 to 26.0). Wearing-off symptoms were present in 33.9% of participants at baseline. No signs of radiological or clinical disease activity were present during follow-up so far.
Conclusions
Personalized extended interval dosing of natalizumab based on trough concentrations has the potential to become a safe, standardized treatment for RRMS patients using natalizumab. Final results of this study are expected in January 2024.