Strategies to estimate and improve drug tolerance in anti-drug antibody assays

Abstract

Background: Drug tolerance of anti-drug antibody (ADA) assays is becoming increasingly important due to the high number of newly emerging long-acting drugs. Methods to estimate and improve drug tolerance in ADA assays are needed. Results: The relevance and precision of drug tolerance estimates in a bridging ELISA depended on characteristics and concentration of the surrogate control antibody together with assay cut point level. Stepwise and coincubation procedures were optimized for drug tolerance and sensitivity by adapting concentrations of reagents used for capture and detection of ADAs. In combination with acid treatment of samples, increase in drug tolerance of over 20-fold was achieved without losing sensitivity in two different assays. Acid treatment reduced drug interference observed in preclinical samples and prevented underestimation of ADA response. Conclusion: In a risk-based approach it may be possible to reliably predict in vivo drug tolerance using carefully chosen surrogate controls. General guidelines for development of drug-tolerant bridging ELISAs are presented.