P918 Can we rely on HLA to predict resistance to biological therapy in Inflammatory Bowel Disease patients?

Abstract

Abstract Background Monoclonal antibodies revolutionized IBD therapy, although some patients do not respond or progressively loose response due to antidrug antibodies. Immunogenicity seems to be related with HLA haplotypes, namely HLA-DQA1*05 allele associated with an increased risk of immunogenicity to anti-TNF therapy in CD. There are no data regarding the association between HLA-DQA1*05 positivity in UC patients and other biological drugs. Objectives We aim to determine HLA-DQA1*05 prevalence in IBD patients and evaluate its association with loss of response to biological therapy. As a secondary endpoint we aim to evaluate the effect of HLA-DQA1*05 genotype in a composite outcome that encompasses clinical, biochemical, and endoscopic remission at week 54. Methods Single center prospective cohort study, including consecutive adult bio-naïve IBD patients followed at IBD consultation, that initiated biological therapy. Data was collected regarding demographic, disease characterization and disease activity at baseline. All patients were screened for HLA-DQA1*05. Pharmacokinetic data was collected, and biological therapy was adjusted based on standardized protocols. Patients were classified as primary non-responders or as secondary non-responders. Response assessment was carried out at week 54 with a composite outcome that encompasses clinical, biochemical, and endoscopic remission. Statistical analysis: Chi-square test; Student’s t-test; Mann Whitney test; Kaplan-Meier survival analysis. Results We included 100 patients (67 CD, 33 UC), of whom 33 primary non-responders, 12 secondary non-responders and 55 achieved w54 of treatment. Patients started anti-TNF (72 patients, 51 Infliximab and 21 Adalimumab), Vedolizumab (18 patients) or Ustekinumab (10 patients), and 26 were on combined therapy. 43 (43%) patients were HLA-DQA1*05 positive. Kaplan-Meier survival analysis revealed no statistically significant differences in therapy persistence between HLA groups in all patients. However, a Kaplan-Meier survival sub analysis revealed patients under Vedolizumab had significant lower therapy persistence if HLA-DQA1*05 positive (p<0.001). UC´s patients revealed tendency to lower therapy persistence if HLA-DQA1*05 positive, although not statistically significant (p=0.051). HLA-DQA1*05 negative patients under Vedolizumab achieved our composite outcome (p<0,001) and patients under anti-TNF revealed a higher response to the composite outcome but without statistical significance. Conclusion HLA-DQA1*05 genotyping demonstrated no impact in therapy persistence, except in the subgroup of patients treated with Vedolizumab. HLA-DQA1*05 negative patients had a higher response to the composite outcome, but with statistical significance only in Vedolizumab subgroup.