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In a phase IIa trial in patients with moderate to severe CD, treatment with brazikumab, an anti\u2010interleukin 23 monoclonal antibody, was associated with clinical improvement. Brazikumab treatment effect was determined to be dependent on the baseline IL\u201022 (BIL22) or baseline C\u2010reactive protein (BCRP; predictive biomarkers), and placebo effect was found to be correlated with the baseline CDAI (a prognostic biomarker). A maximal total inhibition on CDAI input function of 50.6% and 42.4% was predicted for patients with extremely high BIL22 or BCRP, compared to a maximal total inhibition of 20.9% and 17.8% for patients with extremely low BIL22 or BCRP, respectively, which were mainly due to the placebo effect. We demonstrated that model\u2010derived baseline biomarker levels that achieve 50% of maximum unbound systemic concentration of 22.8\u2009pg\/mL and 8.03\u2009mg\/L for BIL22 and BCRP as the cutoffs to select subpopulations can effectively identify high\u2010response subgroup patients with improved separation of responders when compared to using the median values as the cutoff. This work exemplifies the utility of pharmacometrics to quantify biomarker\u2010driven responses in biologic therapies and distinguish between predictive and prognostic biomarkers, complementing clinical efforts of identifying subpopulations with higher likelihood of response to brazikumab.<\/jats:p>","DOI":"10.1002\/psp4.13044","type":"journal-article","created":{"date-parts":[[2023,9,11]],"date-time":"2023-09-11T06:56:27Z","timestamp":1694415387000},"page":"1945-1959","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Combining pharmacometric models with predictive and prognostic biomarkers for precision therapy in Crohn's disease: A case study of brazikumab"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5031-9480","authenticated-orcid":false,"given":"Nan","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Bioengineering and Therapeutic Sciences University of California San Francisco  San Francisco California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming Liang","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Bioengineering and Therapeutic Sciences University of California San Francisco  San Francisco California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Quantitative Pharmacology, Clinical Pharmacology &amp; 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