{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T09:19:51Z","timestamp":1787822391234,"version":"build-2784847793"},"reference-count":30,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T00:00:00Z","timestamp":1778284800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T00:00:00Z","timestamp":1778284800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Objectives<\/jats:title>\n                    <jats:p>Firsekibart (formerly GenSci048 or genakumab) is a humanized anti\u2010IL\u20101\u03b2 monoclonal antibody developed for acute gouty flares in patients unsuitable for standard therapies. This study characterized its population pharmacokinetics (PopPK), assessing covariate effects, and established exposure\u2013response (E\u2010R) relationships to guide dosing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Data from four clinical trials involving 296 subjects (2287 concentrations) were pooled to develop a PopPK model using NONMEM with stepwise covariate screening. A one\u2010compartment model with sequential zero\u2010 and first\u2010order absorption was utilized. E\u2010R analyses were conducted to assess efficacy (dVAS\n                      <jats:sub>72h<\/jats:sub>\n                      , defined as achieving \u226550% reduction in Visual Analog Scale [VAS] scores from baseline measured at 72\u2009h) and safety (dyslipidaemia\/hepatic dysfunction\/infectious and invasive diseases) using logistic regression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Body weight significantly affected clearance and distribution volume. Hepatic or renal impairment caused exposure differences of less than 27%. No exposure\u2010dependent safety trends were identified across the evaluated exposure range.<\/jats:p>\n                    <jats:p>\n                      Although exposure\u2013response trends were observed across the broader dose range, the gradient within the exposure range achieved by 195\u2013200\u2009mg was shallow, consistent with a plateau. Simulations indicated that at the 200\u2010mg dose, more than 95% of patients attained exposures associated with at least 85% probability of achieving dVAS\n                      <jats:sub>72h<\/jats:sub>\n                      . Firsekibart also markedly reduced flare recurrence over 12\u2009weeks compared with the control group.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Firsekibart demonstrated predictable pharmacokinetics, a favourable safety profile, and robust efficacy coverage at the 200\u2010mg fixed dose. These findings support fixed\u2010dosing for patients with acute gout flares who are intolerant of, unsuitable for, or inadequately responsive to standard\u2010of\u2010care therapies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bcp.70607","type":"journal-article","created":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T07:01:04Z","timestamp":1778310064000},"page":"3082-3092","source":"Crossref","is-referenced-by-count":0,"title":["Population pharmacokinetics and exposure\u2013response modelling of firsekibart (GenSci048) in patients with acute gout flare: Implications for fixed\u2010dose optimization"],"prefix":"10.1002","volume":"92","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2609-6058","authenticated-orcid":false,"given":"Kun","family":"Wang","sequence":"first","affiliation":[{"name":"Shanghai Qiangshi Information Technology Co., Ltd.  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Yang","sequence":"additional","affiliation":[{"name":"Center for Drug Clinical Research Shanghai University of Traditional Chinese Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengyan","family":"Xu","sequence":"additional","affiliation":[{"name":"Shanghai Qiangshi Information Technology Co., Ltd.  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Liu","sequence":"additional","affiliation":[{"name":"Shanghai Qiangshi Information Technology Co., Ltd.  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianhong","family":"Luo","sequence":"additional","affiliation":[{"name":"Changchun GeneScience Pharmaceutical Co., Ltd.  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