Background: The success of anti-tumor necrosis factor (TNF) drug strategies in the treatment of inflammatory bowel disease (IBD) is altered by the development of anti-drug antibodies that reduce their efficacy. Studies have shown that the HLA-DQA1⋆05 allele increases the risk of immunogenicity to anti-TNF drugs approximately twofold.
Objective: Analyze whether the presence of the HLA-DQA1⋆05 allele is associated with the development of immunogenicity and to evaluate the disease response to anti-TNF drugs (infliximab (IFX) and adalimumab (ADA)), according to the presence of this allele.
Design: This is an observational retrospective cohort study, single center, to determine the impact of HLA-DQA1⋆05 on disease activity in patients with IBD at the Hospital Universitario Virgen Macarena.
Methods: In total, 200 IBD patients were included: 109 treated with IFX and 91 with ADA. Data were collected using the computerized medical records from the DIRAYA program of the Servicio Andaluz de Salud. Response-defined as improvement-and remission-defined as the disappearance of symptoms and analytical/endoscopic signs-were assessed using activity indices (partial Mayo, Harvey-Bradshaw) in all patients. Anti-TNF drug levels were also determined, as well as the presence or absence of anti-IFX and anti-ADA antibodies. The reporting of this study conforms to the Strengthening the Reporting of Observational Studies in Epidemiology statement.
Results: The HLA-DQA1⋆05 haplotype was present in 70 (35%) patients, including 39 (36%) treated with IFX and 31 (34%) with ADA. The risk of withdrawal, intensification, as well as antibody development, was higher in patients carrying the allele and on treatment with IFX or ADA.
Conclusion: In our study, we demonstrated that there is an increased risk of immunogenicity in patients carrying the HLA-DQA1⋆05 genotype, which would support the idea of screening for this genetic variant before starting anti-TNF therapy, as its prevalence is high in the general population and increases the risk of treatment discontinuation due to loss of response.
Keywords: HLA-DQA1⋆05; anti-TNF; anti-drug antibodies; inflammatory bowel disease.
Carriage of HLA-DQA1⋆05 haplotype is associated with higher risk of infratherapeutic drug concentration and higher immunogenicity in patients undergoing treatment with anti-TNF for inflammatory bowel disease Anti-TNF drugs are commonly used to treat inflammatory bowel disease (IBD), but their effectiveness can be reduced if patients develop antibodies against them. This study investigated whether a specific gene, HLA-DQA1⋆05, increases the likelihood of forming these antibodies and affects the response to anti-TNF drugs, such as infliximab (IFX) and adalimumab (ADA).The study analyzed 200 IBD patients, including those treated with IFX and ADA. Researchers assessed drug levels, the presence of antibodies, and how well patients responded to the treatment. They found that 35% of the patients carried the HLA-DQA1⋆05 gene. Those with this gene had a higher risk of treatment issues, such as needing to stop or switch medications, and were more likely to develop antibodies.The findings suggest that screening for the HLA-DQA1⋆05 gene before starting anti-TNF therapy could be beneficial. Identifying patients with this gene might help predict who is at higher risk for treatment failure and allow for better management of their care.
© The Author(s), 2024.