P196 Pre-treatment antibodies to infliximab and adalimumab are common but are not associated with anti-TNF treatment failure

Abstract Background Anti-TNF treatment failure is common. Primary non-response and loss of response are frequently caused by low anti-TNF drug levels mediated, principally, by the formation of anti-drug antibodies which can be mitigated by concomitant immunomodulator use. Previous small studies in patients with IBD suggest that antibodies formed prior to treatment can bind drug and impair the pharmacokinetics, efficacy and safety of the anti-TNF drugs. We sought to determine the prevalence, neutralising capacity and clinical relevance of pre-treatment antibodies to infliximab and adalimumab in in anti-TNF-naïve patients with active luminal Crohn’s disease. Methods The Personalised Anti-TNF Therapy in Crohn’s Disease study (PANTS) is a UK-wide, multicentre, prospective observational cohort reporting treatment failure rates of the anti-TNF drugs infliximab and adalimumab in Crohn’s disease. The prevalence of antibodies to infliximab and adalimumab at baseline in all patients were measured using IDKmonitor ELISA assays and neutralising capacity in positive cases was determined using the iLite™ cell-based assays. Associations between baseline antibody status, subsequent immunogenicity and drug levels, and response status were assessed using Mann-Whitney U tests and chi-squared analyses, respectively. Results In the PANTS cohort, at baseline, pre-treatment anti-TNF antibodies were detected in 7.3% (112/1525) patients. Pre-treatment antibodies to infliximab were more common (6.3% 96/1525 vs 2.4% 36/1525, p<0.01) and of higher levels (median (IQR) infliximab: 23.9 (14.2 – 55.2) AU/ml vs adalimumab: 7.2 (6.3 – 10.4) AU/ml, p<0.0001) than adalimumab. A minority (1.3% (20/1525)) of patients had anti-drug antibody reactivity to both drugs. None of the detected anti-drug antibodies had demonstrable anti-TNF neutralising capacity detected by our iLite™ cell-based assay. No associations were seen between baseline antibody reactivity, subsequent immunogenicity, drug levels or response status at week 14 or week 52. Conclusion Pre-treatment anti-drug antibodies are common. However, they do not neutralise anti-TNF drug activity invitro, promote drug clearance or influence clinical response to anti-TNF drugs. Further work is required to understand this cross-reactivity and to determine the exact nature of the antibodies detected in drug naïve individuals.