{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:24:03Z","timestamp":1790835843881,"version":"4.1.0"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2024,8,20]],"date-time":"2024-08-20T00:00:00Z","timestamp":1724112000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006483","name":"AbbVie","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006483","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,1,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background and Aims<\/jats:title>\n                  <jats:p>Anti-tumor necrosis factor (anti-TNF) therapies are commonly prescribed treatments for Crohn\u2019s disease (CD) and ulcerative colitis (UC). Many patients treated with anti-TNF therapy eventually develop anti-drug antibodies (ADAs). Understanding the factors associated with immunogenicity in anti-TNF-treated patients can help guide treatment. The Humira SERENE studies were Phase 3 trials investigating adalimumab induction regimens in CD and UC patients.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We imputed alleles for 7 HLA genes in 1100 patients from the SERENE CD and SERENE UC trials. We then tested these alleles for association with time to immunogenicity. Subsequently, we tested loci significantly associated with immunogenicity for their association with patients who had consistently low drug serum concentrations.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>This study replicated the association of HLA-DQA1*05 with time to immunogenicity (hazard ratio [HR] 1.42, p\u2005=\u20052.22E-06). Specifically, HLA-DQA1*05:05 was strongly associated (HR 1.76, p\u2005=\u20052.02E-10) and we detected a novel association represented by HLA-DRB1*01:02 (HR 3.16, p\u2005=\u20052.92E-07). Carriage of HLA-DQA1*05:05 and HLA-DRB1*01:02 was associated with patients who experienced consistently low adalimumab trough concentrations (HLA-DQA1*05:05: odds ratio [OR] 1.98, p\u2005=\u20050.0049; HLA DRB1*01:02: OR 7.06, p\u2005=\u20057.44E-05).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>We found a significant association between alleles at genes in the human HLA locus and the formation of adalimumab immunogenicity and low adalimumab drug serum concentrations in large clinical studies of CD and UC patients. This work extends previous findings in CD to UC and directly shows a genetic association in patients with low drug concentrations. This work builds on existing literature to suggest that genetic screening could be a useful tool for clinicians concerned with patient anti-TNF immunogenicity.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Clinical Trial Registration Numbers<\/jats:title>\n                  <jats:p>SERENE CD (NCT02065570), SERENE UC (NCT02065622).<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ecco-jcc\/jjae129","type":"journal-article","created":{"date-parts":[[2024,8,20]],"date-time":"2024-08-20T16:57:26Z","timestamp":1724173046000},"source":"Crossref","is-referenced-by-count":12,"title":["HLA-DQA1*05 Associates With Anti-Tumor Necrosis Factor Immunogenicity and Low Adalimumab Trough Concentrations in Inflammatory Bowel Disease Patients From the SERENE Ulcerative Colitis and Crohn\u2019s Disease Studies"],"prefix":"10.1093","volume":"19","author":[{"given":"Mark","family":"Reppell","sequence":"first","affiliation":[{"name":"AbbVie Inc. , North Chicago, IL ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuwen","family":"Zheng","sequence":"additional","affiliation":[{"name":"AbbVie Inc. , North Chicago, IL ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingeborg","family":"Dreher","sequence":"additional","affiliation":[{"name":"AbbVie Deutschland GmbH & Co, KG , Ludwigshafen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas","family":"Blaes","sequence":"additional","affiliation":[{"name":"AbbVie Deutschland GmbH & Co, KG , Ludwigshafen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elina","family":"Regan","sequence":"additional","affiliation":[{"name":"AbbVie Inc. , North Chicago, IL ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Haslberger","sequence":"additional","affiliation":[{"name":"AbbVie Deutschland GmbH & 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