{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,2]],"date-time":"2025-08-02T19:27:22Z","timestamp":1754162842841,"version":"3.41.2"},"reference-count":16,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T00:00:00Z","timestamp":1742342400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Sarilumab (interleukin\u20106 receptor inhibitor) is approved in the United States and Europe for polymyalgia rheumatica (PMR). This study characterized sarilumab pharmacokinetics (PK) and assessed the influence of intrinsic and extrinsic factors on PK in patients with PMR and giant cell arteritis (GCA). Exposure\u2010responses analyses were conducted to evaluate the PK\u2010pharmacodynamic (PD) relationships of sarilumab with key efficacy and safety endpoints in patients with PMR (NCT03600818). Population (Pop) PK analysis was conducted using pooled PK data from two phase III studies including 58 patients with PMR and 40 with GCA (NCT03600805). This Pop PK model was developed by re\u2010estimating parameters from a previous rheumatoid arthritis (RA) model. The main source of intrinsic PK variability in patients with PMR was body weight, with decreasing weight causing increased sarilumab exposure. The population mean apparent clearance for patients with PMR was lower than for patients with RA due to higher albumin, lower creatinine clearance, and lower C\u2010reactive protein (CRP) in PMR than in RA. Individual exposures at steady state overlapped among patients with PMR, GCA, and RA. PK\u2010PD relationships showed that greater sarilumab C<jats:sub>trough<\/jats:sub> in patients with PMR were associated with increasing total sIL\u20106R\u03b1 and decreasing CRP. There was a slight increase in patients achieving sustained remission at Week 52 and a decrease in absolute neutrophil count with increasing sarilumab C<jats:sub>trough<\/jats:sub> plateauing at 20\u201025 mg\/L. The PD effect of sarilumab plateaued at C<jats:sub>trough<\/jats:sub> of 20\u201025 mg\/L for target saturation, efficacy, and safety endpoints, supporting a dosage of 200 mg every 2 weeks for PMR.<\/jats:p>","DOI":"10.1002\/jcph.70019","type":"journal-article","created":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T07:34:23Z","timestamp":1742369663000},"page":"988-998","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Population Pharmacokinetics and Exposure\u2010Response Analyses of Sarilumab in Patients with Polymyalgia Rheumatica"],"prefix":"10.1002","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8953-1112","authenticated-orcid":false,"given":"Christine","family":"Xu","sequence":"first","affiliation":[{"name":"Sanofi  Bridgewater NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5759-428X","authenticated-orcid":false,"given":"William S.","family":"Denney","sequence":"additional","affiliation":[{"name":"Human Predictions LLC  Cambridge MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Liu","sequence":"additional","affiliation":[{"name":"Sanofi  Bridgewater NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer","family":"Sloane","sequence":"additional","affiliation":[{"name":"Sanofi  Cambridge MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Remco","family":"Diab","sequence":"additional","affiliation":[{"name":"Sanofi  Rotkreuz Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hisham","family":"Abdallah","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals, Inc.  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