P0837 Prevalence of the HLA-DQA1*05 phenotype in a cohort of Spanish patients with Inflammatory Bowel Disease, and its association with the response to first anti-TNF therapy in real-world settings
Authors: De Castro Parga M L , Ucha P , Sanroman L , Santamaría A , Hernández V , Martínez-Cadilla J , García-Morales N , Rodríguez-Prada I ,   GUT Diseases Galicia Sur Research Institute (IIS Galicia Sur) SERGAS.UVIGO
Published: January 2025

Abstract

Background
Anti-tumor necrosis factor (anti-TNF) drugs usually represent the first line of biological therapy in inflammatory bowel disease (IBD) patients. The presence of the HLA-DQA1*05 allele has been linked to a higher risk of immunogenicity and the development of anti-drug antibodies. This condition may increase the likelihood of primary treatment failure or loss of response to anti-TNF medications. However, clinical data on this topic are scarce and often contradictory.

Methods
Prospective, single-center cohort study in bio-naive IBD patients receiving the first anti-TNF medication for IBD activity from 1 January 2020 to 31 December 2023. PCR-SSP using the HLA-Ready Gene Coeliac Disease kit detected the DQA1*05 allele in a saliva sample. The result was positive if the DQA1*05:01:01,03 or DQA1*05:01:01,05,08 alleles were present. Patients were followed from first dose to discontinuation or last visit. The primary endpoint was anti-TNF persistence, considering as treatment failures, IBD patients with primary or secondary loss of response, and anti-TNF discontinuation due to adverse events. An appropriate statistical analysis was performed using survival Kaplan-Meier curves to assess anti-TNF persistence.

Results
We included 209 patients:108 men (51.7%), mean age 43.5 (17) and time since diagnosis 6.5 (10) years. Ulcerative colitis 39.2% and Crohn´s Disease 60.8%. As the first anti-TNF, 107 patients received adalimumab (51.2%) and 101 infliximab. Baseline demographics for the cohort are summarized in Table 1. At anti-TNF initiation, 29.2% and 58% of patients were on immunosuppressants and systemic steroids, respectively. HLA-DQA1*05 was determined in 205 patients with 38.8% (81) positive, 54.5% (114) negative and 4.8% (10) null results. HLA carriers did not differ according to gender, age or IBD clinical phenotype. A total of 87 patients (41.6%) discontinued treatment during a median follow-up of 22.3 (10-36) months, mostly infliximab 59,3% vs 41% (p=0.009). At 12 and 24 weeks, primary anti-TNF failure was reported in 24 (11.5%) and 34 (16.3%) patients, respectively. Anti-TNF was discontinued in another 23 patients (11%) because of loss of response and in 22 (10.5%) for serious adverse events, mainly infusion reactions (5.7%). The mean persistence of first anti-TNF was similar in allele carriers 36.7 CI95%(31.5-41.9) versus naive 33.8 CI 95%(29.6-38.1) months (Figure 1).

Conclusion
HLA-DQA1*05 ihaplotype is carried by 40%, of bio-naive Spahish IBD patients, a similar prevalence to that obtained in other western IBD populations.
HLA-DQA1*05 carrier status was not associated with IBD clinical phenotypes or persistence on the first anti-TNF treatment.

References
Spencer EA, Stachelski J, Dervieux T et al. Failure to achieve target drug concentrations during induction and not HLA-DQA1∗05 carriage is associated with antidrug antibody formation in patients with Inflammatory Bowel Disease. Gastroenterology. 2022;162(6):1746-48.
Pascual-Oliver A, Casas-Deza D, Cuarán C et al. HLA-DQA1*05 was not associated with primary nonresponse or loss of response to first anti-TNF in real-world Inflammatory Bowel Disease patients. Inflamm Bowel Dis.2024; 3:30 (6):922-929.