{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T14:28:19Z","timestamp":1790692099587,"version":"4.1.0"},"reference-count":25,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,5,24]],"date-time":"2020-05-24T00:00:00Z","timestamp":1590278400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Ravulizumab, a novel long\u2010acting complement component 5 (C5) inhibitor administered every 8\u00a0weeks (q8w), was non\u2010inferior to eculizumab for all efficacy outcomes in two randomised, open\u2010label, phase 3 trials in C5 inhibitor\u2010na\u00efve (Study 301) and eculizumab\u2010experienced (Study 302) adult patients with paroxysmal nocturnal haemoglobinuria (PNH). This pre\u2010specified analysis characterised ravulizumab pharmacokinetics (PK), pharmacodynamics (PD; free C5 levels), and PD differences between medications (Study 301, <jats:italic>n<\/jats:italic>\u00a0=\u00a0246; Study 302, <jats:italic>n<\/jats:italic>\u00a0=\u00a0195). Ravulizumab PK parameters were determined using non\u2010compartmental analysis. Serum free C5 was quantified with a Gyros\u2010based fluorescence assay (ravulizumab) and an electrochemiluminescence ligand\u2010binding assay (eculizumab). Ravulizumab PK parameters were numerically comparable in both studies; the median time to maximum concentrations ranged from 2\u00b73 to 2\u00b78 and 2\u00b73 to 2\u00b76\u00a0h in studies 301 and 302, respectively. Ravulizumab steady\u2010state serum concentrations were achieved immediately after the first dose and sustained throughout treatment. For ravulizumab, the mean (SD) <jats:italic>post hoc<\/jats:italic> terminal elimination half\u2010life was 49\u00b77\u00a0(8\u00b79)\u00a0days. Serum free C5 concentrations &lt;0\u00b75\u00a0\u00b5g\/ml were achieved after the first ravulizumab dose and sustained throughout treatment in both studies. In a minority of patients, free C5 concentrations &lt;0\u00b75\u00a0\u00b5g\/ml were not consistently achieved with eculizumab in either study. Ravulizumab q8w was more consistent in providing immediate, complete, sustained C5 inhibition than eculizumab every\u20102\u2010weeks in patients with PNH.<\/jats:p>","DOI":"10.1111\/bjh.16711","type":"journal-article","created":{"date-parts":[[2020,5,25]],"date-time":"2020-05-25T04:18:12Z","timestamp":1590380292000},"page":"476-485","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":70,"title":["Pharmacokinetic and pharmacodynamic effects of ravulizumab and eculizumab on complement component 5 in adults with paroxysmal nocturnal haemoglobinuria: results of two phase 3 randomised, multicentre studies"],"prefix":"10.1111","volume":"191","author":[{"given":"R\u00e9gis","family":"Peffault de Latour","sequence":"first","affiliation":[{"name":"French Reference Center for Aplastic Anemia and PNH Hematology\u2010Bone Marrow Transplantation H\u00f4pital Saint\u2010Louis AP\u2010HP Paris France"},{"name":"Universit\u00e9 Paris Diderot Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Brodsky","sequence":"additional","affiliation":[{"name":"Division of Hematology Department of Medicine Johns Hopkins University School of Medicine Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Ortiz","sequence":"additional","affiliation":[{"name":"Alexion Pharmaceuticals, Inc. Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4744-5109","authenticated-orcid":false,"given":"Antonio M.","family":"Risitano","sequence":"additional","affiliation":[{"name":"Hematology Department of Clinical Medicine and Surgery Federico II University Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun H.","family":"Jang","sequence":"additional","affiliation":[{"name":"Sungkyunkwan University School of Medicine Samsung Medical Center Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Hillmen","sequence":"additional","affiliation":[{"name":"Department of Haematology St. James's University Hospital Leeds UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander D.","family":"Kulagin","sequence":"additional","affiliation":[{"name":"Pavlov First Saint Petersburg State Medical University St. Petersburg Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Austin G.","family":"Kulasekararaj","sequence":"additional","affiliation":[{"name":"Department of Haematological Medicine King\u2019s College Hospital NIHR\/Wellcome King\u2019s Clinical Research Facility London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott T.","family":"Rottinghaus","sequence":"additional","affiliation":[{"name":"Alexion Pharmaceuticals, Inc. 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