{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T14:29:43Z","timestamp":1787495383334,"version":"build-2736575974"},"reference-count":15,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,12,2]],"date-time":"2021-12-02T00:00:00Z","timestamp":1638403200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Guselkumab is an anti\u2010interleukin\u201023 human monoclonal antibody effective in treating psoriatic arthritis (PsA). To characterize the pharmacokinetics (PKs) and exposure\u2010response relationship of guselkumab in PsA, population PKs, and exposure\u2010response modeling, analyses were conducted using data from pivotal phase III studies of subcutaneous guselkumab in patients with PsA. The observed serum concentration\u2010time data of guselkumab were adequately described by a one\u2010compartment linear PK model with first\u2010order absorption and elimination. Covariates identified as contributing to the observed guselkumab PK variability were body weight and diabetes comorbidity; however, the magnitude of the effects of these covariates was not considered clinically relevant, and dose adjustment was not warranted for the patient population investigated. Positive exposure\u2010response relationships were demonstrated with landmark and longitudinal exposure\u2010response analyses between guselkumab exposure and clinical efficacy end points (American College of Rheumatology [ACR] 20%, 50%, and 70% improvement criteria and Investigator\u2019s Global Assessment [IGA] of psoriasis) at weeks 20 and\/or 24, with no clinically relevant differences observed in improvement of PsA signs and symptoms between the two guselkumab treatment regimens evaluated (100\u00a0mg every 4\u00a0weeks or 100\u00a0mg at weeks 0 and 4, then every 8\u00a0weeks). Baseline Disease Activity Score in 28 joints (DAS28), Psoriasis Area and Severity Index (PASI) score, and\/or C\u2010reactive protein level were identified as influencing covariates on guselkumab exposure\u2010response model parameters. These results provide a comprehensive evaluation of subcutaneous guselkumab PKs and exposure\u2010response relationship that supports the dose regimen of 100\u00a0mg at weeks 0 and 4, then every 8\u00a0weeks in patients with PsA.<\/jats:p>","DOI":"10.1111\/cts.13197","type":"journal-article","created":{"date-parts":[[2021,12,2]],"date-time":"2021-12-02T03:44:18Z","timestamp":1638416658000},"page":"749-760","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Population pharmacokinetics and exposure\u2010response modeling analyses of guselkumab in patients with psoriatic arthritis"],"prefix":"10.1111","volume":"15","author":[{"given":"Yang","family":"Chen","sequence":"first","affiliation":[{"name":"Clinical Pharmacology &amp; Pharmacometrics Janssen Research &amp; Development, LLC  Spring House Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Miao","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology &amp; Pharmacometrics Janssen Research &amp; Development, LLC  Spring House Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chyi\u2010Hung","family":"Hsu","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology &amp; Pharmacometrics Janssen Research &amp; Development, LLC  Spring House Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanli","family":"Zhuang","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology &amp; Pharmacometrics Janssen Research &amp; Development, LLC  Spring House Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexa","family":"Kollmeier","sequence":"additional","affiliation":[{"name":"Immunology Clinical Research Janssen Research &amp; Development, LLC  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenhua","family":"Xu","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology &amp; Pharmacometrics Janssen Research &amp; Development, LLC  Spring House Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honghui","family":"Zhou","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology &amp; Pharmacometrics Janssen Research &amp; Development, LLC  Spring House Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amarnath","family":"Sharma","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology &amp; Pharmacometrics Janssen Research &amp; Development, LLC  Spring House Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,12,2]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2817"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20030896"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kex186"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.170.11.5438"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1063"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30263-4"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30265-8"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1582"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10928-012-9288-7"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1208\/ps040427"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.393"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/psp.2014.15"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.5414\/CPP48830"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10928-017-9534-0"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12286"}],"container-title":["Clinical and Translational Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.13197","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cts.13197","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.13197","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,26]],"date-time":"2023-08-26T23:12:16Z","timestamp":1693091536000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1111\/cts.13197"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,2]]},"references-count":15,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2022,3]]}},"alternative-id":["10.1111\/cts.13197"],"URL":"https:\/\/doi.org\/10.1111\/cts.13197","archive":["Portico"],"relation":{},"ISSN":["1752-8054","1752-8062"],"issn-type":[{"value":"1752-8054","type":"print"},{"value":"1752-8062","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,2]]},"assertion":[{"value":"2021-08-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-11-03","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-12-02","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}