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We modeled the clinical utility of pre-treatment HLA-DQA1*05:01 and HLA-DQA1*05:05 allele subtype testing to guide immunomodulator use in patients with Crohn\u2019s disease treated with an anti-TNF.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The Personalised Anti-TNF Therapy in Crohn\u2019s Disease study is a UK-wide, prospective observational study of infliximab and adalimumab in anti-TNF-na\u00efve patients with active Crohn\u2019s disease. Rates of drug-clearing antibody development, defined by the presence of anti-TNF antibodies and undetectable drug levels, were estimated using the Kaplan\u2013Meier method. Genetic association tests were performed using Cox proportional hazards regression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>About 40% of participants carried an actionable HLA-DQA1*05 allele subtype. HLA-DQA1*05:01 (hazard ratio [HR] 1.87 [95% CI: 1.37-2.53], P\u2009&amp;lt;\u2009.0001) and HLA-DQA1*05:05 (HR 2.45 [95% CI: 1.32-4.54], P\u2009=\u2009.004) were the most significant allele subtypes associated with the development of drug-clearing antibodies in infliximab- and adalimumab-treated patients, respectively. Immunomodulator use increased the time to drug-clearing antibodies in all patients treated with infliximab. In adalimumab-treated patients, only individuals who carried the HLA-DQA1*05:05 allele subtype benefited from combination immunomodulator use with a number needed to treat of 4.6 (95% CI: 2.4-20.5) to prevent one episode of a drug-clearing antibody.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Pre-treatment four-digit HLA testing informs on anti-TNF treatment choice and immunomodulator use. In HLA-DQA1*05:01 carriers, adalimumab monotherapy should be used and infliximab avoided. In HLA-DQA1*05:05 carriers, infliximab or adalimumab can be used with a concomitant immunomodulator. In patients who do not carry either HLA-DQA1*05:01 or HLA-DQA1*05:05, adalimumab monotherapy or infliximab with a concomitant immunomodulator are recommended.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ecco-jcc\/jjaf233","type":"journal-article","created":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T13:00:44Z","timestamp":1765976444000},"source":"Crossref","is-referenced-by-count":3,"title":["Clinical utility of pre-treatment four-digit-resolution HLA genotyping to guide anti-tumor necrosis factor choice and concomitant immunomodulator use"],"prefix":"10.1093","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7231-0804","authenticated-orcid":false,"given":"Phoebe","family":"Hodges","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Royal Devon University Healthcare NHS Foundation Trust , Exeter,","place":["United Kingdom"]},{"name":"Exeter IBD and Pharmacogenetics Research Group, University of Exeter , 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