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We utilized clinical data from studies of an anti\u2010OSM monoclonal antibody (GSK2330811) in healthy volunteers (<jats:italic>n<\/jats:italic>\u2009=\u200949) and systemic sclerosis patients (<jats:italic>n<\/jats:italic>\u2009=\u200935), to quantitatively determine the link between OSM and alterations in red blood cell (RBC) and platelet production. Longitudinal changes in hematopoietic variables (including RBCs, reticulocytes, platelets, erythropoietin, and thrombopoietin) were linked in a physiology\u2010based model, to capture the long\u2010term effects and variability of therapeutic OSM neutralization on human hematopoiesis. Free serum OSM stimulated precursor cell production through sigmoidal relations, with higher maximum suppression (I<jats:sub>max<\/jats:sub>) and OSM concentration for 50% suppression (IC<jats:sub>50<\/jats:sub>) for platelets (89.1% [95% confidence interval: 83.4\u201393.0], 6.03\u2009pg\/mL [4.41\u20138.26]) than RBCs (57.0% [49.7\u201364.0], 2.93\u2009pg\/mL [2.55\u20133.36]). Reduction in hemoglobin and platelets increased erythro\u2010 and thrombopoietin, respectively, prompting reticulocytosis and (partially) alleviating OSM\u2010restricted hematopoiesis. The physiology\u2010based model was substantiated by preclinical data and utilized in exploration of once\u2010weekly or every other week dosing regimens. Predictions revealed an (for the indication) unacceptable occurrence of grade 2 (67% [58\u201376], 29% [20\u201338]) and grade 3 (17% [10\u201325], 3% [0\u20137]) anemias, with limited thrombocytopenia. Individual extent of RBC precursor modulation was moderately correlated to skin mRNA gene expression changes. The physiological basis and consideration of interplay among hematopoietic variables makes the model generalizable to other drug and nondrug scenarios, with adaptations for patient populations, diseases, and therapeutics that modulate hematopoiesis or exhibit risk of anemia and\/or thrombocytopenia.<\/jats:p>","DOI":"10.1002\/cpt.3246","type":"journal-article","created":{"date-parts":[[2024,3,19]],"date-time":"2024-03-19T10:10:27Z","timestamp":1710843027000},"page":"703-715","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Predicting the Long\u2010Term Effects of Therapeutic Neutralization of Oncostatin M on Human Hematopoiesis"],"prefix":"10.1002","volume":"116","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1804-2703","authenticated-orcid":false,"given":"Anders","family":"Thorsted","sequence":"first","affiliation":[{"name":"Department of Pharmacy Uppsala University  Uppsala Sweden"},{"name":"Clinical 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