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Decrease of natalizumab drug levels after switching from intravenous to subcutaneous administration in patients with
Alyssa A Toorop1, Zoé L E van Kempen2, Maurice Steenhuis3
1Department of Neurology, MS Center Amsterdam, Amsterdam UMC Location VUMC, Amsterdam, The Netherlands a.toorop@amsterdamumc.nl.
Switching to subcutaneous natalizumab may lower drug levels in multiple sclerosis patients. Monitoring natalizumab trough levels is advised for those on extended intervals or with specific patient factors after switching administration routes.
Area of Science:
- Neurology
- Pharmacology
- Immunology
Background:
- Natalizumab is an effective treatment for multiple sclerosis (MS).
- Subcutaneous (SC) natalizumab was approved in Europe in 2021 as an alternative to intravenous (IV) administration.
- Concerns exist regarding natalizumab SC efficacy and FDA rejection, prompting investigation into drug level variations.
Purpose of the Study:
- To evaluate natalizumab trough drug levels in patients switching from IV to SC administration.
- To assess the impact of different treatment intervals on drug levels post-switch.
- To compare drug levels between IV and SC natalizumab administration routes.
Main Methods:
- Analysis of data from the NEXT-MS trial, including 15 participants who switched to SC natalizumab.
- Frequent measurement of natalizumab drug levels and antidrug antibodies (ADAs) after switching.
- Comparison of drug levels using linear mixed model analyses.
Main Results:
- SC natalizumab resulted in average drug levels 55% lower than IV administration.
- Three patients experienced very low trough drug levels on extended intervals after switching to SC.
- No natalizumab ADAs were detected, and no MS disease activity was observed in participants on SC natalizumab.
Conclusions:
- Natalizumab trough drug levels can decrease upon switching from IV to SC administration.
- Monitoring is recommended for patients with low IV natalizumab levels, higher BMI, or on extended intervals when switching to SC.
- These findings highlight the importance of personalized monitoring following a route change in natalizumab therapy.
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