{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T17:53:09Z","timestamp":1785779589074,"version":"3.56.0"},"reference-count":45,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,12,25]],"date-time":"2025-12-25T00:00:00Z","timestamp":1766620800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,12,25]],"date-time":"2025-12-25T00:00:00Z","timestamp":1766620800000},"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":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Juvenile idiopathic arthritis (JIA) is a chronic autoimmune disease that negatively affects ~100,000 children under the age of 16 in the United States. About ~30% of these patients fail first\u2010line drug therapy with low\u2010dose methotrexate (MTX) due to poor tolerability or lack of efficacy. The\n                    <jats:italic>SLCO1B1*14<\/jats:italic>\n                    allele is associated with increased MTX clearance and has been linked to reduced overall drug exposure and nonresponse to MTX in JIA patients. Herein, we describe transgenic\n                    <jats:italic>hSLCO1B1*14<\/jats:italic>\n                    and\n                    <jats:italic>hSLCO1B1*1<\/jats:italic>\n                    DBA1\/J\n                    <jats:italic>mSlco1b2<\/jats:italic>\n                    knock\u2010out mice, which we used to assess arthritic response to MTX using the collagen\u2010induced arthritis model. Mass spectrometry\u2010based proteomics analysis revealed that OATP1B1 protein abundance was 2.1\u2010fold higher in\n                    <jats:italic>hSLCO1B1*14<\/jats:italic>\n                    mice compared to\n                    <jats:italic>hSLCO1B1*1<\/jats:italic>\n                    mice. Following treatment with 1\u2009mg\/kg MTX for 3\u2009weeks,\n                    <jats:italic>hSLCO1B1*14<\/jats:italic>\n                    mice exhibited a 39% increase in median arthritic disease burden (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.02) and a 22% reduction in MTX AUC (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.14) compared to\n                    <jats:italic>hSLCO1B1*1<\/jats:italic>\n                    mice. Pharmacokinetic modeling estimated that the\n                    <jats:italic>hSLCO1B1*14<\/jats:italic>\n                    mice would need a 30% higher dose to equalize exposure and response to\n                    <jats:italic>hSLCO1B1*1<\/jats:italic>\n                    mice. When\n                    <jats:italic>hSLCO1B1*14<\/jats:italic>\n                    mice received 1.3\u2009mg\/kg MTX, the arthritic disease burden and overall MTX exposure were less than the 1\u2009mg\/kg MTX in\n                    <jats:italic>hSLCO1B1*1<\/jats:italic>\n                    mice, reinforcing that differences in MTX elimination and therapeutic response can be accounted for by using pharmacogenetic\u2010guided dosing of MTX in JIA patients.\n                  <\/jats:p>","DOI":"10.1111\/cts.70449","type":"journal-article","created":{"date-parts":[[2025,12,25]],"date-time":"2025-12-25T09:40:36Z","timestamp":1766655636000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacogenetic\n                    <i>hSLCO1B1*14<\/i>\n                    \u2010Guided Dosing of Methotrexate in Transgenic Arthritic Mice Normalizes Exposure and Response"],"prefix":"10.1111","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5973-6560","authenticated-orcid":false,"given":"Felicia","family":"Gooden","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Physiology, and Neurobiology University of Cincinnati College of Medicine  Cincinnati Ohio USA"},{"name":"Division of Translational and Clinical Pharmacology Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brennan D.","family":"Meier","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences University of Cincinnati  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7907-3734","authenticated-orcid":false,"given":"Griffin D.","family":"Shaffer","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Physiology, and Neurobiology University of Cincinnati College of Medicine  Cincinnati Ohio USA"},{"name":"Division of Translational and Clinical Pharmacology Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim","family":"Gibson","sequence":"additional","affiliation":[{"name":"Mass Spectrometry &amp; Bioanalysis Core Children's Mercy Hospital  Kansas City Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Toren","sequence":"additional","affiliation":[{"name":"Mass Spectrometry &amp; Bioanalysis Core Children's Mercy Hospital  Kansas City Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7655-6094","authenticated-orcid":false,"given":"Nieko C.","family":"Punt","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology University Medical Center Groningen, University of Groningen  Groningen the Netherlands"},{"name":"Medimatics  Maastricht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4001-7534","authenticated-orcid":false,"given":"Sandhya","family":"Subash","sequence":"additional","affiliation":[{"name":"Division of Translational and Clinical Pharmacology Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7248-6714","authenticated-orcid":false,"given":"Dilip K.","family":"Singh","sequence":"additional","affiliation":[{"name":"Division of Translational and Clinical Pharmacology Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9090-0912","authenticated-orcid":false,"given":"Bhagwat","family":"Prasad","sequence":"additional","affiliation":[{"name":"Division of Translational and Clinical Pharmacology Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"},{"name":"Department of Pediatrics University of Cincinnati College of Medicine  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6417-3961","authenticated-orcid":false,"given":"Laura B.","family":"Ramsey","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Toxicology, and Therapeutic Innovation Children's Mercy Hospital  Kansas City Missouri USA"},{"name":"Department of Psychiatry and Behavioral Neuroscience University of Cincinnati College of Medicine  Cincinnati Ohio USA"},{"name":"Department of Pediatrics University of Missouri\u2010Kansas City  Kansas City Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5178-2397","authenticated-orcid":false,"given":"Zachary L.","family":"Taylor","sequence":"additional","affiliation":[{"name":"Division of Translational and Clinical Pharmacology Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"},{"name":"Department of Pediatrics University of Cincinnati College of Medicine  Cincinnati Ohio USA"},{"name":"Cancer and Blood Diseases Institute Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,25]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)60363-8"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s42358-020-00138-4"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.2165\/00148581-200608060-00003"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/anr.1780320604"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(199803)41:3<381::AID-ART2>3.0.CO;2-3"},{"issue":"9","key":"e_1_2_9_7_1","first-page":"1573","article-title":"Plasma Levels After Oral Methotrexate in Children With Juvenile Rheumatoid Arthritis","volume":"20","author":"Ravelli A.","year":"1993","journal-title":"Journal of Rheumatology"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1993.tb04158.x"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-75655-9"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2021050598"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200342020-00003"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2705"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-08-452839"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.20.4156"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.129668.111"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/acr2.1008"},{"key":"e_1_2_9_17_1","first-page":"295","article-title":"The Mouse Model of Collagen\u2010Induced Arthritis","volume":"102","author":"Brand D. 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