Antidrug antibodies to adalimumab do not associate with immunologically related adverse events.

Introduction: Unwanted immune responses (UIRs) to biologics can negatively impact treatment efficacy and pharmacokinetics and/or induce adverse events (AEs). We characterized the UIR profile of adalimumab (ADL) using data from a phase 3, randomized, interchangeability study of reference ADL (ADL-REF; Humira Methods: Eligible patients (18-70 years, moderate-to-severe active RA) received ADL-REF from weeks 0-10 (lead-in period) then were randomized 1:1 to: 3 switches between PF-06410293 and ADL-REF or continuous ADL-REF treatment until week 32. As interchangeability of PF-06410293 with ADL-REF was previously demonstrated, data were combined across groups to describe the development of antidrug antibodies (ADAs) and their impact on pharmacokinetics and immunologically related AEs. Pharmacokinetic endpoints included maximum observed serum concentration (C Results: Of 427 randomized patients, 59% were ADA-positive, 52% had persistent ADA, 14% were NAb-positive, and 10% had persistent NAb. In most patients, ADA/NAb first developed within 16 weeks of ADL treatment regardless of pre-existing (baseline day 1) ADA. ADA/NAb titers stabilized by week 16 without boosters. C Conclusions: Presence of ADA (with or without NAb) was associated with lower drug concentrations and faster clearance but not with the development of immunologically related AEs. Clinical trial registration: ClinicalTrials.gov, identifier NCT0423021.