{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T17:50:45Z","timestamp":1789321845018,"version":"build-2803163510"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T00:00:00Z","timestamp":1760313600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009745","name":"Royal Devon and Exeter NHS Foundation Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009745","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010311","name":"Guts UK","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010311","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003522","name":"Crohn's and Colitis UK","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003522","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Cure crohn's's Colitis"},{"DOI":"10.13039\/100019211","name":"AbbVie","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100019211","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012781","name":"Merck Sharp and Dohme","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100012781","id-type":"DOI","asserted-by":"crossref"}]},{"name":"NAPP Pharmaceuticals Ltd UK"},{"name":"Pfizer Ltd US"},{"name":"Celltrion Healthcare South Korea"},{"name":"NIHR Clinical Doctoral Research Fellowship"},{"name":"Wellcome Trust GW4-CAT Fellowship","award":["222850\/Z\/21\/Z"],"award-info":[{"award-number":["222850\/Z\/21\/Z"]}]},{"name":"National Institute for Health and Care Research (NIHR) Exeter Biomedical Research Centre"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,11,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>We sought to determine the prevalence, clinical impact, neutralizing capacity, and cross-reactivity of pre-existing antibodies to infliximab and adalimumab in antitumor necrosis factor (TNF) treatment-na\u00efve patients with active luminal crohn disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The prevalence of antibodies to infliximab and adalimumab at entry to the \u201cPersonalised Anti-TNF Therapy in Crohn's Disease Study\u201d (PANTS) were measured using the drug-tolerant IDKmonitor Total antidrug antibody ELISAs. Neutralizing capacity in positive cases was determined using iLite\u2122 cell-based assays.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Pre-existing antibodies to infliximab were more common (6.3%, 96\/1525 vs 2.4%, 36\/1525, P &amp;lt; 0.01) and detectable at higher concentrations [median (IQR) 23.9 (14.2\u201355.2) AU\/mL vs 7.2 (6.3\u201310.4) AU\/mL, P &amp;lt; 0.0001] to infliximab than adalimumab. A few patients [1.3% (95% CI 0.6\u20131.8) 20\/1525] had antidrug antibody reactivity to both drugs. None of the detected antidrug antibodies had demonstrable anti-TNF neutralizing capacity. No associations were seen between pre-existing antibody positivity, adverse drug reactions, drug levels, or response status at weeks 14 or 54 or subsequent immunogenicity. Cross-reactivity with rheumatoid factor and antimouse antibodies was detected (&amp;gt;10 IU\/mL) in 6.6% (95% CI 3.2\u201313.0) (7\/106) and 17.0% (95% CI 10.5\u201325.2) (19\/112) of patients with pre-existing antibodies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Pre-existing antidrug antibodies are common but do not neutralize anti-TNF drug activity in vitro, promote drug clearance, or influence clinical response to anti-TNF drugs. Further work is required to understand this cross-reactivity and to determine the exact nature of the antibodies detected in drug-na\u00efve individuals.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jalm\/jfaf149","type":"journal-article","created":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T12:47:39Z","timestamp":1758113259000},"page":"1580-1592","source":"Crossref","is-referenced-by-count":1,"title":["Understanding Anti-TNF Treatment Failure: Pre-Existing Antidrug Antibodies Are Common but Do Not Neutralize Drug Activity In Vitro or Influence Clinical Response to Infliximab or Adalimumab in Patients with Crohn Disease"],"prefix":"10.1093","volume":"10","author":[{"given":"Rachel","family":"Nice","sequence":"first","affiliation":[{"name":"Blood Sciences Academic Department, Royal Devon University Healthcare Trust , Exeter ,","place":["United Kingdom"]},{"name":"Exeter Inflammatory Bowel Disease and Pharmacogenetics Research Group, University of Exeter , Exeter ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4201-4879","authenticated-orcid":false,"given":"Simeng","family":"Lin","sequence":"additional","affiliation":[{"name":"Exeter Inflammatory Bowel Disease and Pharmacogenetics Research Group, University of Exeter , Exeter ,","place":["United Kingdom"]},{"name":"Department of Gastroenterology, Royal Devon University Healthcare Trust , Exeter ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0207-6706","authenticated-orcid":false,"given":"Neil","family":"Chanchlani","sequence":"additional","affiliation":[{"name":"Exeter Inflammatory Bowel Disease and Pharmacogenetics Research Group, University of Exeter , Exeter ,","place":["United Kingdom"]},{"name":"Department of Gastroenterology, Royal Devon University Healthcare Trust , Exeter ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0965-9587","authenticated-orcid":false,"given":"Claire","family":"Bewshea","sequence":"additional","affiliation":[{"name":"Exeter Inflammatory Bowel Disease and Pharmacogenetics Research Group, University of Exeter , Exeter ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas A","family":"Kennedy","sequence":"additional","affiliation":[{"name":"Exeter Inflammatory Bowel Disease and Pharmacogenetics Research Group, University of Exeter , Exeter ,","place":["United Kingdom"]},{"name":"Department of Gastroenterology, Royal Devon University Healthcare Trust , Exeter ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6058-5528","authenticated-orcid":false,"given":"Tariq","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Exeter Inflammatory Bowel Disease and Pharmacogenetics Research Group, University of Exeter , Exeter ,","place":["United Kingdom"]},{"name":"Department of Gastroenterology, Royal Devon University Healthcare Trust , Exeter ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul G","family":"Winyard","sequence":"additional","affiliation":[{"name":"Inflammation Research Group, University of Exeter Medical School , Exeter ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Goodhand","sequence":"additional","affiliation":[{"name":"Exeter Inflammatory Bowel Disease and Pharmacogenetics Research Group, University of Exeter , Exeter ,","place":["United Kingdom"]},{"name":"Department of Gastroenterology, Royal Devon University Healthcare Trust , Exeter ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3559-6660","authenticated-orcid":false,"given":"Timothy J","family":"McDonald","sequence":"additional","affiliation":[{"name":"Blood Sciences Academic Department, Royal Devon University Healthcare Trust , Exeter ,","place":["United Kingdom"]},{"name":"Exeter Inflammatory Bowel Disease and Pharmacogenetics Research Group, University of Exeter , Exeter ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,10,13]]},"reference":[{"key":"2025110423210831200_jfaf149-B1","author":"U.S. Department of Health and Human Services, FDA. 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