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

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Abstract
Summary: 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: Forty per cent of all participants were HLADQA1*05A>G variant carriers, with 79% of participants with infliximab antibodies carrying at least one variant allele. The risk of infliximab antibody formation was higher in HLADQA1*05A>G variant carriers (adjusted HR = 7.29, 95% confidence interval (CI) = 2.97‐17.191, P = 1.46 × 10−5) independent of age, sex, weight, dose and co‐immunosuppression with an immunomodulator. Variant carrier status was associated with an increased risk of infliximab loss of response (adjusted HR = 2.34, 95% CI = 1.41‐3.88, P = .001) and discontinuation (adjusted HR = 2.27, 95% CI = 1.46‐3.43, P = 2.53 × 10−4) 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.
Funding Information
  • Lawson Health Research Institute (IRF‐05‐19)
  • Academic Medical Organization of Southwestern Ontario (INN18‐005, S17‐004)

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