DOI: 10.1177/13524585261500350 ISSN: 1352-4585
Emergence of natalizumab anti-drug antibodies during extended interval dosing in a patient with multiple sclerosis: A case report
Liza M. Y. Gelissen, Stefan P. H. van den Berg, Thomas P. C. Dorlo, Gertjan Wolbink, Bob W. van Oosten, Joep Killestein, Zoé L. E. van Kempen, Theo RispensBackground:
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.