Carriage of the HLA-DQA1*05 haplotype is associated with a higher risk of infratherapeutic drug concentration and higher immunogenicity in patients undergoing treatment with anti-TNF for inflammatory bowel disease
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 an...
| Autores: | , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2024 |
| País: | España |
| Institución: | Universidad de Sevilla (US) |
| Repositorio: | idUS. Depósito de Investigación de la Universidad de Sevilla |
| OAI Identifier: | oai:idus.us.es:11441/173086 |
| Acceso en línea: | https://hdl.handle.net/11441/173086 https://doi.org/10.1177/17562848241278145 |
| Access Level: | acceso abierto |
| Palabra clave: | HLA-DQA1*05 haplotype Inflammatory bowel disease Anti-tumor necrosis factor (TNF) Immunogenicity |
| Sumario: | 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 orADA. 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. |
|---|