Impact Of Hladqa1*05 And Hladqa1*03 On Safety And Loss Of Response To Anti-Tnf In Patients With Inflammatory Bowel Disease

Background: HLADQA1*05 is recently associated with heightened immunogenicity to anti-TNF. Our aims were to determine whether HLADQ1*05 is a risk factor for primary non-response, loss of response (LOR) or adverse events (AE) to first-line anti-TNFα in patients with inflammatory bowel disease.

Methods: We performed a retrospective observational study enrolling biologic naïve patients with Crohn´s disease and ulcerative colitis who initiated adalimumab or infliximab from 2000 to 2021. HLA-DQA1 genotype was determined in all patients and immunogenicity in 98 patients.

Results: We enrolled 408 patients who started first-line infliximab (n=211) and adalimumab (n=197), with a mean follow-up of 7.6 years. Primary response at week 24 occurred in 347 (85.0%), LOR in 133 (38.3%) and AE in 93 (22.8%). The HLADQA1*05 was identified in 185 (43.3%) patients. In multivariate analyses, no risk factors were identified for primary response. HLADQA1*05 was an independent risk factor for LOR (aHR=1.80, 95%CI=1.21-2.67) and immunogenicity (aOR=3.44, 95% CI=1.12-11.92). HLADQA1*03 was a protective factor against LOR (aHR=0.42, 95%CI=0.20-0.88). Stratified analysis by anti-TNF type showed that HLADQA1*05 increased the risk of LOR to infliximab but not to adalimumab and HLADQA1*03 decreased the risk of LOR to adalimumab but not to infliximab. Female sex, infliximab and the co-presentation of at least one allele of the HLADQA1*03 and HLADQA1*05 were risk factors for AE.

Conclusions: HLADQA1*05 is associated with a higher risk of LOR and immunogenicity, particularly to infliximab. HLADQA1*03 seems to play a protective role against LOR, particularly to adalimumab. Female sex and infliximab are risk factors for AE.