Emergence of natalizumab anti-drug antibodies during extended interval dosing in a patient with multiple sclerosis: A case report
BACKGROUND: We present a natalizumab-treated patient with multiple sclerosis (MS) who developed neutralizing anti-drug antibodies (ADAs) after years of treatment following introduction of extended interval dosing (EID). OBJECTIVES: To gain insight into how this sudden ADA development occurred. METHODS: A pharmacokinetic model was used to evaluate the relation between natalizumab concentration and ADA production. RESULTS: EID from 4 to 6 weeks resulted in unexpectedly low natalizumab trough concentrations accompanied by increasing ADAs. Modeling suggested ADA production was stimulated by declining natalizumab concentrations. CONCLUSIONS: EID may result in increased ADA production, causing ADA-mediated clearance of natalizumab and risking new MS activity.
Authors
- Liza M. Y. Gelissen (ORCID: https://orcid.org/0009-0004-4864-1429)
- Zoé L. E. van Kempen (ORCID: https://orcid.org/0000-0001-9557-5381)
- Theo Rispens (ORCID: https://orcid.org/0000-0001-9600-1312)
- Thomas P. C. Dorlo (ORCID: https://orcid.org/0000-0003-3076-8435)
- Bob W. van Oosten (ORCID: https://orcid.org/0000-0003-4536-6201)
- Joep Killestein (ORCID: https://orcid.org/0000-0002-6347-5957)
- Stefan Berg (ORCID: https://orcid.org/0009-0004-2181-094X)
- Gertjan Wolbink
Institutions
- Uppsala University (SE)
- Sanquin (NL)
- Amsterdam Neuroscience (NL)
- Amsterdam University Medical Centers (NL)
- Amsterdam institute for Immunology and Infectious Diseases (NL)
- Vrije Universiteit Amsterdam (NL)
- Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
Publication Details
- Journal
- Multiple Sclerosis Journal
- Published
- 2026-11-02
- DOI
- https://doi.org/10.1177/13524585261500350
- Primary Topic
- Multiple Sclerosis Research Studies
- Type
- article
- Field-Weighted Citation Impact
- 0.00