TPMT and HLA-DQ Allelic Variants in Relation to Drug Response, Safety and Need for Therapy Optimization in Pediatric Inflammatory Bowel Disease

Background/Objectives: Pharmacogenetics examines genome variability and its influence on drug efficacy and toxicity, forming the foundation for personalized medicine. Patients with inflammatory bowel disease (IBD) treated with azathioprine with thiopurine S-methyltransferase (TPMT) deficiency are at an increased risk of drug-related toxic effects. Variability in the HLA-DQA1 and DQB1 alleles may lead to an inadequate therapeutic response. This study aimed to determine the significance of TPMT and HLA-DQ Allelic Variants in therapy optimization planning. Methods: A retrospective study was conducted to determine TPMT gene polymorphism and the presence of HLA-DQA1 and HLA-DQB1 alleles in children diagnosed with IBD and treated at the Institute for Child and Youth Health Care of Vojvodina in May 2023. Results: The study included 104 children with a mean age of 13.71 ± 3.1 years, with a balanced gender distribution. A TPMT mutation was identified in only one child. The most common HLA-DQA1 alleles were *01 (49%) and *05 (28.8%), while the most frequent allele at the HLA-DQB1 locus was 03 (15.4%). The presence of the HLA-DQA105 allele was associated with the development of anti-drug antibodies against anti-TNF therapy (RR: 1.23; 95% CI: 1.03–1.50), while the presence of HLA-DQA101 was significantly more frequent in children on optimized therapeutic regimens (RR: 1.63; 95% CI: 1.13–2.10). Conclusions: Prior to the initiation of azathioprine therapy, TPMT genotyping should be performed to prevent adverse effects and ensure optimal drug dosing. Identification of the HLA-DQA105 and HLA-DQA101 alleles plays an important role in the planning of biological therapy regimens, including decisions on dose escalation or interval shortening.