{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T21:53:50Z","timestamp":1790286830180,"version":"4.1.0"},"reference-count":20,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T00:00:00Z","timestamp":1739404800000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Macrophage activation syndrome (MAS) is a life\u2010threatening form of secondary haemophagocytic lymphohistiocytosis (HLH) associated with rheumatic diseases, most commonly Still's disease. This study aimed to develop a population pharmacokinetic (PK)\/pharmacodynamic (PD) model for emapalumab, a fully human monoclonal antibody that targets interferon\u2010gamma (IFN\u03b3), in patients with MAS associated with Still's disease. A two\u2010compartment disposition model based on data from patients with primary HLH administered emapalumab (1\u2009mg\/kg every 3\u2009days, with possible increases to 3, 6 or 10\u2009mg\/kg) was re\u2010estimated for patients with MAS administered emapalumab (6\u2009mg\/kg, then 3\u2009mg\/kg every 3\u2009days until day 15 and twice weekly until day 28). An exploratory population PK\/PD analysis comprising patients' PD data for total IFN\u03b3, chemokine C\u2010X\u2010C motif ligand 9 (CXCL9) and ferritin was performed. Emapalumab clearance was generally linear and independent of total IFN\u03b3 levels in patients with MAS (<jats:italic>n<\/jats:italic>\u2009=\u200914). Estimated baseline levels of CXCL9 (a marker of IFN\u03b3 activity), soluble interleukin\u20102 receptor \u03b1 (sIL\u20102R\u03b1; a marker of hyperinflammation) and ferritin (a clinical marker of MAS disease activity) were 8400, 6550 and 15,300\u2009\u03bcg\/L, respectively. All three PD markers responded rapidly to changes in emapalumab concentration. Emapalumab almost completely suppressed CXCL9, sIL2\u2010R\u03b1, and ferritin production (estimated reduction in synthesis rate: 98.3%, 87%, and 99.6%, respectively). Population PK\/PD modeling indicated that emapalumab rapidly suppresses markers of hyperinflammation in patients with MAS associated with Still's disease. Emapalumab dosing regimen used in clinical trials in patients with MAS is unlikely to need adjustment.<\/jats:p>","DOI":"10.1111\/cts.70163","type":"journal-article","created":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T04:16:55Z","timestamp":1739420215000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Emapalumab in Patients With Macrophage Activation Syndrome Associated With Still's Disease: A Population Pharmacokinetic\/Pharmacodynamic Analysis"],"prefix":"10.1111","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3249-5434","authenticated-orcid":false,"given":"Patrick","family":"Brossard","sequence":"first","affiliation":[{"name":"Sobi  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,2,13]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/asheducation-2015.1.177"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/asheducation-2013.1.605"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-03-278127"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2018894618"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-01-551622"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0000000000005361"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)61048-X"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2015.179"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00119"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.42037"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard-2023-224123"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-018-0029-z"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2776(07)96002-2"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.15133"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1911326"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard-2022-223739"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40744-024-00669-y"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.663329"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-021-00694-z"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.30778"}],"container-title":["Clinical and Translational Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.70163","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:04:49Z","timestamp":1760162689000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1111\/cts.70163"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2]]},"references-count":20,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,2]]}},"alternative-id":["10.1111\/cts.70163"],"URL":"https:\/\/doi.org\/10.1111\/cts.70163","archive":["Portico"],"relation":{},"ISSN":["1752-8054","1752-8062"],"issn-type":[{"value":"1752-8054","type":"print"},{"value":"1752-8062","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2]]},"assertion":[{"value":"2024-11-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70163"}}