{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T04:07:14Z","timestamp":1790827634535,"version":"4.1.0"},"reference-count":32,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T00:00:00Z","timestamp":1749686400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["UEG Journal"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Perianal Crohn's disease (CD) remains challenging to treat despite the increasing number of advanced therapies. Advanced dual\u2010targeted therapy has emerged as a new treatment option in CD, but no data are available for perianal CD. The aim of this study was to evaluate the effectiveness and safety of advanced dual\u2010targeted therapy for anoperineal fistulas (APFs) in CD patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>We prospectively included all consecutive patients receiving an advanced dual\u2010targeted therapy for APFs from August 2019 to December 2023 in a single tertiary perianal CD centre. The primary outcome was clinical effectiveness. Secondary outcomes were patients' treatment perception, radiological effectiveness, luminal disease effectiveness, impact on extra\u2010intestinal manifestations, and safety. Factors associated with complete clinical remission of APFs were identified using logistic regression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 33 patients were included. The most frequently used advanced dual\u2010targeted therapy was a combination of infliximab and ustekinumab (75.8%). After a median follow\u2010up of 27.4\u00a0months, 48.5% and 97.0% of patients were in complete clinical remission and reported a perceived improvement, respectively. Complete radiological remission was achieved in 24.2% of the patients. A concomitant improvement in luminal intestinal involvement was observed in 46.1% of cases, and in extra\u2010digestive manifestations in 45.8% of cases. Treatment tolerance was considered good or very good in 90.9% of cases. Associated anal ulcers and long\u2010term exposure to antibiotics were associated with a lower likelihood of complete clinical remission for fistulas.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These findings suggest that advanced dual\u2010targeted therapy is a valid option with a good safety profile for the treatment of refractory APFs. Larger studies are required to identify the most effective combination.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ueg2.70059","type":"journal-article","created":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T10:40:28Z","timestamp":1749724828000},"page":"1491-1501","source":"Crossref","is-referenced-by-count":8,"title":["Effectiveness and Safety of Advanced Dual\u2010Targeted Therapy in Refractory Perianal Crohn's Disease"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5219-827X","authenticated-orcid":false,"given":"Nadia","family":"Fathallah","sequence":"first","affiliation":[{"name":"Service de proctologie m\u00e9dico\u2010chirurgicale H\u00f4pital Paris Saint\u2010Joseph  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6710-5933","authenticated-orcid":false,"given":"Mario","family":"Pagano","sequence":"additional","affiliation":[{"name":"Service de proctologie 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