{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T08:32:43Z","timestamp":1765960363308,"version":"3.41.2"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2024,11,21]],"date-time":"2024-11-21T00:00:00Z","timestamp":1732147200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,6,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>HLADQA1*05 is recently associated with heightened immunogenicity to anti-tumor necrosis factor (TNF\u03b1). We aimed to determine whether HLADQ1*05 is a risk factor for primary non-response, loss of response (LOR), or adverse events (AE) to first-line anti-TNF\u03b1 in patients with inflammatory bowel disease.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We performed a retrospective observational study enrolling biologic na\u00efve patients with Crohn\u2019s disease and ulcerative colitis who initiated adalimumab or infliximab from 2000 to 2021. HLA-DQA1 genotype was determined in all patients and immunogenicity in 98 patients.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We enrolled 408 patients who started first-line infliximab (n\u2005=\u2005211) and adalimumab (n\u2005=\u2005197), with a mean follow-up of 7.6 years. Primary response at Week 24 occurred in 347 (85.0%), LOR in 133 (38.3%), and AE in 93 (22.8%). The HLADQA1*05 was identified in 185 (43.3%) patients. In multivariate analyses, no risk factors were identified for primary response. HLADQA1*05 was an independent risk factor for LOR (adjusted hazard ratio [aHR]\u2005=\u20051.80, 95% CI\u2005=\u20051.21-2.67) and immunogenicity (aOR\u2005=\u20053.44, 95% CI\u2005=\u20051.12-11.92). HLADQA1*03 was a protective factor against LOR (aHR\u2005=\u20050.42, 95% CI\u2005=\u20050.20-0.88). Stratified analysis by anti-TNF type showed that HLADQA1*05 increased the risk of LOR to infliximab but not to adalimumab and HLADQA1*03 decreased the risk of LOR to adalimumab but not to infliximab. Female sex, infliximab, and the co-presentation of at least one allele of the HLADQA1*03 and HLADQA1*05 were risk factors for AE.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>HLADQA1*05 is associated with a higher risk of LOR and immunogenicity, particularly to infliximab. HLADQA1*03 seems to play a protective role against LOR, particularly adalimumab. Female sex and infliximab are risk factors for AE.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ecco-jcc\/jjae178","type":"journal-article","created":{"date-parts":[[2024,11,21]],"date-time":"2024-11-21T15:15:12Z","timestamp":1732202112000},"source":"Crossref","is-referenced-by-count":2,"title":["Impact of HLADQA1*05 and HLADQA1*03 on Safety and Loss of Response to Anti-Tumor Necrosis Factor in Patients With Inflammatory Bowel Disease"],"prefix":"10.1093","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3193-4936","authenticated-orcid":false,"given":"Julia","family":"L\u00f3pez De-La-Cruz","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Lozano Blesa University Hospital , Zaragoza ,","place":["Spain"]},{"name":"Arag\u00f3n Health Research Institute (IIS Arag\u00f3n) , Zaragoza ,","place":["Spain"]},{"name":"School of Medicine, University of Zaragoza , Zaragoza ,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0076-3529","authenticated-orcid":false,"given":"Fernando","family":"Gomoll\u00f3n","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Lozano Blesa University Hospital , Zaragoza ,","place":["Spain"]},{"name":"Arag\u00f3n Health Research Institute (IIS Arag\u00f3n) , Zaragoza ,","place":["Spain"]},{"name":"School of Medicine, University of Zaragoza , Zaragoza ,","place":["Spain"]},{"name":"CIBEREHD , Zaragoza ,\u00a0","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Javier","family":"Louro","sequence":"additional","affiliation":[{"name":"Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet , Stockholm ,","place":["Sweden"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan","family":"L\u00f3pez P\u00e9rez","sequence":"additional","affiliation":[{"name":"Department of Immunology, Lozano Blesa University Hospital , Zaragoza ,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda Mercedes","family":"Nocito\u00a0Colon","sequence":"additional","affiliation":[{"name":"Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet , Stockholm ,","place":["Sweden"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatriz","family":"Gallego Llera","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Lozano Blesa University Hospital , Zaragoza ,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2670-3922","authenticated-orcid":false,"given":"Sandra","family":"Garc\u00eda-Mateo","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Lozano Blesa University Hospital , Zaragoza ,","place":["Spain"]},{"name":"Arag\u00f3n Health Research Institute (IIS Arag\u00f3n) , Zaragoza ,","place":["Spain"]},{"name":"School of Medicine, University of Zaragoza , Zaragoza ,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0857-8117","authenticated-orcid":false,"given":"Samuel J","family":"Mart\u00ednez-Dom\u00ednguez","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Lozano Blesa University Hospital , Zaragoza ,","place":["Spain"]},{"name":"Arag\u00f3n Health Research Institute (IIS Arag\u00f3n) , Zaragoza ,","place":["Spain"]},{"name":"School of Medicine, University of Zaragoza , Zaragoza ,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda Concepci\u00f3n","family":"Aso Gonzalvo","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Lozano Blesa University Hospital , Zaragoza ,","place":["Spain"]},{"name":"Arag\u00f3n Health Research Institute (IIS Arag\u00f3n) , Zaragoza 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