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.