{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T13:43:41Z","timestamp":1792763021937,"version":"4.5.0"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T00:00:00Z","timestamp":1792713600000},"content-version":"vor","delay-in-days":22,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007028","name":"Leona M. and Harry B. Helmsley Charitable Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007028","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and aims<\/jats:title>\n                    <jats:p>In perianal fistulizing Crohn\u2019s disease (PFCD), higher infliximab (IFX) serum concentrations are associated with improved outcomes. PFCD patients frequently require dose intensification to reach recommended therapeutic targets. IFX pharmacokinetics (PK) in PFCD have not been previously characterized. We hypothesized that drug clearance (CL) is increased in PFCD compared to luminal Crohn\u2019s disease (LCD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients with PFCD and LCD starting standard-dose intravenous IFX (5\u2009mg\/kg at weeks 0, 2, and 6, thereafter every 8\u2009weeks) were enrolled. At every visit, serum samples were collected until week 52 to measure IFX trough levels (TL) and anti-drug antibodies. A population PK model was constructed using nonlinear mixed-effects modeling and adjusted for clinically relevant covariates.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 148 patients were included (62 PFCD, 86 LCD) with 756 serum samples analyzed. IFX PK was described by a two-compartment model with linear elimination. After adjusting for dose, weight, serum albumin, and anti-drug antibodies, population PK modeling revealed a 23% increase in IFX CL among patients with progressive perianal fistulas during the first 14\u2009weeks (P\u2009=\u2009.007). During induction, recommended target IFX TL was achieved in fewer PFCD than LCD patients (43% vs 57%, P\u2009=\u2009.04). At week 14, PFCD patients had lower median IFX TL than LCD (2.9 vs 4.8\u2009\u03bcg\/mL, P\u2009=\u2009.02), with fewer PFCD patients reaching phenotype-specific target TL (9% vs 46%, P\u2009&amp;lt;\u2009.001) compared to LCD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The presence of perianal fistulas increases IFX CL in patients with Crohn\u2019s disease, resulting in significantly lower and frequently subtherapeutic serum concentrations after standard induction dosing.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ecco-jcc\/jjag151","type":"journal-article","created":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T13:36:58Z","timestamp":1792762618000},"source":"Crossref","is-referenced-by-count":0,"title":["Perianal fistulizing Crohn\u2019s disease increases infliximab clearance and causes low infliximab exposure (ATLANTIC)"],"prefix":"10.1093","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1001-1291","authenticated-orcid":false,"given":"Lieven G M","family":"Mulders","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3599-3618","authenticated-orcid":false,"given":"Suzanne I","family":"Anjie","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manon","family":"Chevallot-Beroux","sequence":"additional","affiliation":[{"name":"Biologics Laboratory, Sanquin Diagnostic Services, Amsterdam,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Floris","family":"Loeff","sequence":"additional","affiliation":[{"name":"Biologics Laboratory, Sanquin Diagnostic Services, Amsterdam,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manon E","family":"Wildenberg","sequence":"additional","affiliation":[{"name":"Tytgat Institute for Liver and Intestinal Research, Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ron A A","family":"Math\u00f4t","sequence":"additional","affiliation":[{"name":"Department of Hospital Pharmacy and Clinical Pharmacology, Amsterdam UMC, University of Amsterdam, Amsterdam,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geert R A M","family":"D\u2019Haens","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krisztina B","family":"Gecse","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,10,23]]},"reference":[{"key":"2026102309365323700_jjag151-B1","doi-asserted-by":"publisher","first-page":"1409","DOI":"10.1038\/ajg.2012.218","article-title":"Serious infection and mortality in patients with Crohn\u2019s disease: more than 5 years of follow-up in the TREAT registry","volume":"107","author":"Lichtenstein","year":"2012","journal-title":"Am J Gastroenterol"},{"key":"2026102309365323700_jjag151-B2","doi-asserted-by":"publisher","first-page":"652","DOI":"10.1038\/nrgastro.2017.104","article-title":"Perianal fistulizing Crohn\u2019s disease: pathogenesis, diagnosis and therapy","volume":"14","author":"Pan\u00e9s","year":"2017","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"2026102309365323700_jjag151-B3","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1053\/gast.2002.32362","article-title":"The natural history of fistulizing Crohn\u2019s disease in Olmsted County, Minnesota","volume":"122","author":"Schwartz","year":"2002","journal-title":"Gastroenterology"},{"key":"2026102309365323700_jjag151-B4","doi-asserted-by":"publisher","first-page":"1130","DOI":"10.1016\/j.cgh.2006.06.021","article-title":"Are perineal and luminal fistulas associated in Crohn\u2019s disease? 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