{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:59:54Z","timestamp":1769561994390,"version":"3.49.0"},"reference-count":18,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,4,14]],"date-time":"2022-04-14T00:00:00Z","timestamp":1649894400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Nonacog alfa, a standard half\u2010life recombinant factor IX (FIX), is used as a prophylactic treatment in severe haemophilia B (SHB) patients. Its half\u2010life determined in clinical studies involving a limited sampling (72\u00a0h) was shown to be rather short. In our clinical practice, we suspected that its half\u2010life could have been underestimated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>We aimed to evaluate nonacog alfa pharmacokinetics in real world clinical practice based on FIX levels in patients receiving prophylaxis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We retrospectively collected data on patients with SHB receiving prophylaxis from eight centres across France. The terminal half\u2010life (THL), time to reach 5\u20132\u00a0IU\/dl and FIX activity at 48, 72 and 96\u00a0h were derived by Bayesian estimations using NONMEM analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results and conclusions<\/jats:title><jats:p>Infusion data (<jats:italic>n<\/jats:italic>\u00a0=\u00a0455) were collected from 64 patients with SHB. The median THL measured in 92 pharmacokinetic (PK) studies was 43.4\u00a0h. In 26 patients \u226412 years of age, 51 PK studies showed a median time to reach 5\u00a0IU\/dl of FIX of 70.5\u00a0h and a median time to reach 2\u00a0IU\/dl of 121.5\u00a0h. In 38 patients 13\u201375 years of age, 41 PK studies showed a median time to reach 5\u00a0IU\/dl of FIX of 92.0\u00a0h and a median time to reach 2\u00a0IU\/dl of 167.5\u00a0h. Extending the sampling beyond 72\u00a0h makes it possible to observe a plateau, with FIX remaining between 2 and 5\u00a0IU\/dl for several days and shows that the THL of nonacog alfa might be longer than previously described.<\/jats:p><\/jats:sec><jats:sec><jats:title>Essentials<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Nonacog alfa terminal half\u2010life (THL) in patients receiving regular prophylaxis was evaluated in clinical practice.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The median THL was estimated to be 36.9\u00a0h for patients aged .8\u201312 years.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The median THL was estimated to be 49.9\u00a0h for patients aged 13\u201375 years.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>For patients aged \u226412 and\u00a0&gt;12 years, the median times to reach 5\u00a0IU\/dl were 70.5 and 92 h, respectively; to reach 3\u00a0IU\/dl, 95.5 and 131.5 h, respectively; to reach 2\u00a0IU\/dl, 121.5 and 167.5 h, respectively.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We suggest that the half\u2010life of nonacog alfa might be longer than previously described in both younger and older patients.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1111\/hae.14560","type":"journal-article","created":{"date-parts":[[2022,4,14]],"date-time":"2022-04-14T10:04:54Z","timestamp":1649930694000},"page":"542-547","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Revised terminal half\u2010life of nonacog alfa as derived from extended sampling data: A real\u2010world study involving 64 haemophilia B patients on nonacog alfa regular prophylaxis"],"prefix":"10.1111","volume":"28","author":[{"given":"Brigitte","family":"Tardy","sequence":"first","affiliation":[{"name":"Centre de Ressources et de Comp\u00e9tence Maladies h\u00e9morragiques CHU Saint\u2010Etienne H\u00f4pital Nord  Saint\u2010Etienne France"},{"name":"Sainbiose, Inserm, U1059 Universit\u00e9 Lyon  Saint\u2010Etienne France"},{"name":"Inserm, CIC 1408 CHU Saint\u2010Etienne H\u00f4pital Nord  Saint\u2010Etienne France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thierry","family":"Lambert","sequence":"additional","affiliation":[{"name":"Centre de R\u00e9f\u00e9rence Maladies h\u00e9morragiques CHU Paris Sud\u2010H\u00f4pital de Bic\u00eatre  Le Kremlin\u2010Bic\u00eatre France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6269-2098","authenticated-orcid":false,"given":"Pierre","family":"Chamouni","sequence":"additional","affiliation":[{"name":"Laboratoire d'H\u00e9matologie Institut de Biologie Clinique CHU de Rouen  Rouen France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aur\u00e9lie","family":"Montmartin","sequence":"additional","affiliation":[{"name":"Sainbiose, Inserm, U1059 Universit\u00e9 Lyon  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