Abstract Background The HLA-DQA1*5 allele has been associated with increased immunogenicity and loss of response to intravenous anti–tumor necrosis factor (anti-TNF) therapy in inflammatory bowel disease (IBD). Evidence on its impact in patients receiving subcutaneous infliximab (IFX-SC) remains limited. This study aimed to evaluate whether HLA-DQA1*5 status influences anti-IFX antibody development, loss of response, serum trough concentrations, dose adjustments, and adverse events in IBD patients under IFX-SC therapy. Methods A retrospective observational study was conducted including IBD patients from a tertiary centre treated with IFX-SC. Demographic, clinical and biochemical data were collected, including HLA-DQA1*05 status, immunomodulator use, IFX trough levels, dose changes, corticosteroid need, hospitalisations, surgeries and adverse events. Univariate and multivariate logistic regression analyses were performed; p 0.05 was considered statistically significant. Results Sixty-five patients were included (ulcerative colitis = 25, Crohn’s disease = 39, unclassified = 1), with a median disease duration of 10 years. HLA-DQA1*5 prevalence was 40% (n = 26). No patient developed anti-IFX antibodies during follow-up. Secondary loss of response at 12 months occurred in 3 (4.6%); dose escalation in 21.5%; de-escalation in 15.4%; and adverse events in 7.7%. Two hospitalisations and one surgery were recorded. HLA-DQA1*5 positivity was not associated with hospitalisation, surgery, loss of response or adverse events (p 0.05). However, HLA-positive patients showed lower IFX concentrations after induction (13 ± 8.8 vs 20 ± 19.6 µg/mL; p = 0.03) and lower trough levels during maintenance (17 14.2–23.7 vs 19.3 16.4–28.6 µg/mL; p = 0.046). Dose escalation was more frequent among HLA-positive patients (26.9% vs 17.9%, p = 0.389), independent of albumin, creatinine or previous/concomitant azathioprine. Conclusion In this cohort of IBD patients treated with IFX-SC, HLA-DQA1*5 was not associated with detectable immunogenicity or clinical loss of response but correlated with lower IFX trough levels and a trend toward more frequent dose escalation.These findings suggest a potential pharmacokinetic influence of HLA-DQA1*05 even in the absence of measurable anti-drug antibodies. Further prospective studies with larger samples are warranted to confirm these results and define their clinical significance. References: 1. Rodríguez-Alcolado L, Grueso-Navarro E, Arias Á, Lucendo AJ, Laserna-Mendieta EJ. Impact of HLA-DQA1*05 Genotype in Immunogenicity and Failure to Treatment with Tumour Necrosis Factor-alpha Antagonists in Inflammatory Bowel Disease: A Systematic Review and Meta-analysis. J Crohns Colitis. 2024;18(7):1034-1052. doi:10.1093/ecco-jcc/jjae006 2. Reppell M, Zheng X, Dreher I, et al. HLA-DQA1*05 Associates With Anti-Tumor Necrosis Factor Immunogenicity and Low Adalimumab Trough Concentrations in Inflammatory Bowel Disease Patients From the SERENE Ulcerative Colitis and Crohn’s Disease Studies. J Crohns Colitis. 2025;19(1):jjae129. doi:10.1093/ecco-jcc/jjae129 3. Fitzgerald AL, McBride J, Robertson H, et al. Switching from intravenous to subcutaneous infliximab enhances trough levels and can facilitate de-escalation of concomitant immunomodulation, irrespective of the HLA DQA1*05 status: a prospective real-world study. J Crohns Colitis. 2025;19(Suppl 1):i2458. doi:10.1093/ecco-jcc/jjae190.1543 Conflict of interest: Ms. Cristiano, Margarida: No conflict of interest Borges Chaves, Carlos: No conflict of interest Santos, Luís: No conflict of interest Lopes, Sandra Maria Fernandes: Mendes, Sofia: No conflict of interest Ferreira, Ana Margarida: No conflict of interest Ferreira, Manuela: No conflict of interest Figueiredo, Pedro: No conflict of interest Portela, Francisco: consulting fees and support from the following companies: Abbvie, Falk, Ferring, Janssen, Lilly, Pfizer, Pharmakern, Takeda and Tillots.
Cristiano et al. (Thu,) studied this question.