HLADQA1*05 genotype predicts anti‐drug antibody formation and loss of response during infliximab therapy for inflammatory bowel disease

BACKGROUND: Anti-drug antibodies (ADAs) are a leading contributor to infliximab loss of response and adverse drug events. It is not feasible to identify patients at risk of antibody formation before initiating infliximab. The genetic variation HLADQA1*05 (rs2097432) has been linked to infliximab antibody formation in Crohn's disease (CD). AIMS: To evaluate the association between HLADQA1*05 and infliximab antibody formation, infliximab loss of response, treatment discontinuation and adverse drug events in patients with inflammatory bowel disease (IBD) METHODS: In a retrospective cohort study, infliximab-exposed patients with IBD (n = 262) were screened for the genetic variation, HLADQA1*05A>G (rs2097432). Risk of infliximab ADA formation, infliximab loss of response, adverse events and discontinuation were assessed in wild-type (GG) and variant-carrying (AG or AA) individuals. RESULTS: ) although not with infliximab-associated adverse drug events. CONCLUSIONS: HLADQA1*05 is independently associated with a high risk of infliximab antibody formation in addition to infliximab loss of response and treatment discontinuation. There may be a role for genotype-guided application of combination therapy in IBD.