HLA-DQA1*05 Allele Carriage and Anti-TNF Therapy Persistence in Inflammatory Bowel Disease.

Autor:	Doherty J; Gastroenterology Department, St James's Hospital, Dublin, Ireland.; Department of Gastroenterology, Tallaght University Hospital, Dublin, Ireland.; INITIative IBD Research Network, Dublin, Ireland., Ryan AW; Genuity Science (Ireland) Limited, Dublin, Ireland., Quinn E; Genuity Science (Ireland) Limited, Dublin, Ireland., Conroy J; Genuity Science (Ireland) Limited, Dublin, Ireland., Dolan J; Genuity Science (Ireland) Limited, Dublin, Ireland., Corcoran R; Gastroenterology Department, St James's Hospital, Dublin, Ireland.; Trinity Academic Gastroenterology Group, School of Medicine, Trinity College Dublin, Ireland., Hara FO; Department of Gastroenterology, Tallaght University Hospital, Dublin, Ireland., Cullen G; Department of Gastroenterology, St Vincent's University Hospital, Dublin, Ireland.; School of Medicine, University College Dublin, Ireland.; INITIative IBD Research Network, Dublin, Ireland., Sheridan J; Department of Gastroenterology, St Vincent's University Hospital, Dublin, Ireland.; School of Medicine, University College Dublin, Ireland.; INITIative IBD Research Network, Dublin, Ireland., Bailey Y; Department of Gastroenterology, Tallaght University Hospital, Dublin, Ireland., Dunne C; Gastroenterology Department, St James's Hospital, Dublin, Ireland., Hartery K; Gastroenterology Department, St James's Hospital, Dublin, Ireland., McNamara D; Department of Gastroenterology, Tallaght University Hospital, Dublin, Ireland.; Trinity Academic Gastroenterology Group, School of Medicine, Trinity College Dublin, Ireland.; INITIative IBD Research Network, Dublin, Ireland., Doherty GA; Department of Gastroenterology, St Vincent's University Hospital, Dublin, Ireland.; School of Medicine, University College Dublin, Ireland.; INITIative IBD Research Network, Dublin, Ireland., Kevans D; Gastroenterology Department, St James's Hospital, Dublin, Ireland.; Trinity Academic Gastroenterology Group, School of Medicine, Trinity College Dublin, Ireland.; Wellcome-HRB Clinical Research Facility, St James's Hospital, Dublin, Ireland.; INITIative IBD Research Network, Dublin, Ireland.
Jazyk:	angličtina
Zdroj:	Inflammatory bowel diseases [Inflamm Bowel Dis] 2024 Jun 27. Date of Electronic Publication: 2024 Jun 27.
DOI:	10.1093/ibd/izae138
Abstrakt:	Introduction: Carriage of the HLA-DQA1*05 allele is associated with development of antidrug antibodies (ADAs) to antitumor necrosis factor (anti-TNF) therapy in patients with Crohn's disease. However, ADA is not uniformly associated with treatment failure. We aimed to determine the impact of carriage of HLA-DQA1*05 allele on outcome of biologic therapy evaluated by drug persistence. Methods: A multicenter, retrospective study of 877 patients with inflammatory bowel disease (IBD) treated with anti-TNF therapy with HLA-DQA1*05 genotypes were generated by imputation from whole genome sequence using the HIBAG package, in R. Primary end point was anti-TNF therapy persistence, (time to therapy failure), segregated by HLA-DQA1*05 allele genotype and development of a risk score to predict anti-TNF therapy failure, incorporating HLA-DQA1*05 allele genotype status (LORisk score). Results: In all, 877 patients receiving anti-TNF therapy were included in our study; 543 (62%) had no copy, 281 (32%) one copy, and 53 (6%) 2 copies of HLA-DQA1*05 allele. Mean time to anti-TNF therapy failure in patients with 2 copies of HLA-DQA1*05 allele was significantly shorter compared with patients with 0 or 1 copy at 700 days' follow-up: 418 vs 541 vs 513 days, respectively (P = .012). Factors independently associated with time to anti-TNF therapy failure included carriage of HLA-DQA1*05 allele (hazard ratio [HR], 1.2, P = .02; female gender HR, 1.6, P < .001; UC phenotype HR, 1.4, P = .009; and anti-TNF therapy type [infliximab], HR, 1.5, P = .002). The LORisk score was significantly associated with shorter time to anti-TNF therapy failure (P < .001). Conclusions: Carriage of 2 HLA-DQA1*05 alleles is associated with less favorable outcomes for patients receiving anti-TNF therapy with shorter time to therapy failure. HLA-DQA1*05 genotype status in conjunction with clinical factors may aid in therapy selection in patients with IBD. (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
Databáze:	MEDLINE
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