{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T14:24:05Z","timestamp":1787408645161,"version":"build-2736575974"},"reference-count":34,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T00:00:00Z","timestamp":1786060800000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Biologic therapies are traditionally regarded as having low potential for drug\u2013drug interactions (DDIs) due to their large molecular size and limited direct involvement with drug\u2010metabolizing enzymes and transporters (DMETs). However, accumulating evidence indicates that these drug products may indirectly modulate DMET activity through cytokine\u2010mediated mechanisms, particularly in the context of inflammatory diseases. Pro\u2010inflammatory cytokines such as interleukin\u20106 have been shown to suppress the expression of cytochrome P450 (CYP) enzymes in\u00a0vitro, most notably CYP3A4, thereby potentially altering the metabolic clearance of concomitant medications. This phenomenon may be pertinent in conditions such as inflammatory bowel disease (IBD) where chronic inflammation and systemic physiological alterations may significantly influence drug disposition. Although the U.S. Food and Drug Administration provides a decision framework to assess large molecule DDI risk based on the mechanism of action, it does not offer a standardized, mechanistic approach for evaluating such interactions. In response, alternative methodologies such as the use of endogenous biomarkers like 4\u03b2\u2010hydroxycholesterol, a proposed surrogate for CYP3A activity, and pharmacokinetic modeling are in exploration to support DDI risk assessment to potentially avoid dedicated clinical trials in patients. This review evaluates current knowledge on biologics\u2010mediated DDIs with a particular focus on drug\u2010disease interactions in IBD. There is an opportunity for a more structured, mechanistically informed evaluation that integrates cytokine profiling and biomarker\u2010based approaches to identify DDI risk and enhance the overall understanding of the degree of interaction and its clinical significance.<\/jats:p>","DOI":"10.1111\/cts.70689","type":"journal-article","created":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T03:45:19Z","timestamp":1786160719000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Drug\u2013Drug Interaction Risk Assessment Strategies for Biologics in Inflammatory Bowel Disease: A Literature\u2010Based Evidence Mini\u2010Review"],"prefix":"10.1111","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3898-4020","authenticated-orcid":false,"given":"Claire","family":"Steinbronn","sequence":"first","affiliation":[{"name":"Merck &amp; Co., Inc.  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