S1956 Therapeutic Drug Monitoring Assays for Risankizumab Drug and Anti-Risankizumab Antibodies

Introduction: Risankizumab (RSK), a humanized monoclonal antibody against the p19 subunit of interleukin 23 (IL23), is used to treat Crohn’s disease (CD) and ulcerative colitis (UC). Therapeutic drug monitoring of biologic drugs and their antibodies can expedite clinical decision-making, improve efficacy, and may lead to reduced cost. Here, analytic performance characteristics of new lab developed electrochemiluminescence immunoassays (ECLIA) for RSK and anti-RSK antibody concentrations are presented. Methods: We developed and validated ECLIA for RSK and its anti-drug antibody (ADA) in accordance with FDA guidance for therapeutic protein immunogenicity testing and bioanalytical method validation. The drug assay utilizes antibodies against RSK and is designed to detect free (ADA-unbound) pharmacodynamically active RSK. The ADA assay measures total binding antibodies (including IgM and IgG) against RSK. Analytical performance including accuracy, precision, lower limit of quantitation (LLOQ), upper limit of quantitation (ULOQ), dilutional linearity, specificity, and drug tolerance (for the ADA assay) was assessed. Results: The RSK drug assay has an analytical measurement range (AMR) of 0.75–60 µg/mL with an 80-fold maximum dilution (maximum quantifiable value of 4,800 µg/mL). LLOQ is 0.75 ug/mL where steady state RSK drug trough levels are about 4-9 µg/mL depending upon dose. There is no cross-reactivity with other biologics used to treat similar diseases or with other anti-IL23 inhibitor drugs. The ADA AMR is 25–5,000 ng/mL with a maximum allowable dilution of 100-fold (maximum reportable concentration of 500,000 ng/mL). Drug tolerance was confirmed by sample recovery of 80–120% for samples with drug levels as high as 120 µg/mL and no cross-reactivity was detected for ADAs to other biologics. All positive ADA samples undergo a confirmatory test step where signal suppression upon the addition of high concentrations of RSK confirms the RSK-specificity of the anti-drug antibodies. Conclusion: This study demonstrates the robust analytic performance of 2 new TDM assays to quantify RSK drug and anti-RSK antibodies. Accurate quantitation of RSK drug enables dose optimization at post-induction and maintenance time points, while this drug-specific, drug tolerant, and high resolution anti-RSK assay allows for accurate immunogenic assessment at signs of lack or loss of response. Together, these TDM assays aim to optimize the use and longevity of RSK through precise drug and immunogenicity monitoring.