TY - JOUR T1 - Clinical relevance of detecting anti-infliximab antibodies with a drug-tolerant assay: post hoc analysis of the TAXIT trial JF - Gut JO - Gut SP - 818 LP - 826 DO - 10.1136/gutjnl-2016-313071 VL - 67 IS - 5 AU - Thomas Van Stappen AU - Niels Vande Casteele AU - Gert Van Assche AU - Marc Ferrante AU - Séverine Vermeire AU - Ann Gils Y1 - 2018/05/01 UR - http://gut.bmj.com/content/67/5/818.abstract N2 - Objective To evaluate the clinical relevance of antidrug antibodies (ADAs) measured using a drug-tolerant assay in a post hoc analysis of the Trough Concentration (TC) Adapted Infliximab Treatment (TAXIT) randomised controlled trial.Design ADA in serum samples (n=221) of 76 patients enrolled in TAXIT, who presented with an infliximab TC <3 µg/mL at screening, were reanalysed after optimisation and at the end of the study using a drug-tolerant ADA assay. Patients underwent dose escalation to achieve therapeutic TCs between 3 µg/mL and 7 µg/mL prior to randomisation. Patients were grouped into quartiles (Q1–4) according to ADA concentration at screening.Results Using a drug-tolerant assay, the immunogenicity detection rate increased from 21% (drug-sensitive assay) to 63% at screening, from 0% to 51% after optimisation and from 3% to 42% at the end of TAXIT. Patients in ADA Q4 required a higher cumulative infliximab dose (2390 (880–2998) mg) to achieve target TCs, resulting in a higher drug cost (€10 712 (4120–13 596)) compared with ADA-negative patients (€2060 (1648–3296)) and patients in ADA Q1/Q2 (€2060 (1648–4120)/€2060 (1751–3296), p<0.001). However, all but one patient belonging to ADA Q4 were also ADA-positive using a drug-sensitive assay.Conclusions Upon dose intensification, low concentration ADAs, not detectable using a drug-sensitive assay, disappear in more than half of the patients over time and are clinically non-relevant. In contrast, high concentration ADAs which are typically also detected in a drug-sensitive assay, persist over time and necessitate a higher cumulative dose and drug cost. In the latter group, proactive drug switching may be more cost-efficient.Clinical Trials Register 2011-002061-38; Post-results. ER -