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Candidate composite endpoint variables were selected by a group of experts and included: lactate dehydrogenase levels as a measure of intravascular hemolysis; complete terminal complement inhibition; absence of major adverse vascular events, including thrombosis; absence of any adverse events leading to death or discontinuation of study treatment; transfusion avoidance; and improvements in fatigue\u2010related quality of life as determined by the Functional Assessment of Chronic Illness Therapy (FACIT)\u2010Fatigue score. From these variables, a novel composite endpoint was constructed and explored using data collected in the ravulizumab PNH Study 301 (NCT02946463). Thresholds were defined and reported for each candidate variable. Five of the six candidate variables were included in the final composite endpoint; the FACIT\u2010Fatigue score was excluded. Composite endpoint criterion was defined as patients meeting all five selected individual component thresholds. All patients in the ravulizumab arm achieved complete terminal complement inhibition and a reduction in lactate dehydrogenase levels; 51.2% and 41.3% of patients in the ravulizumab arm and eculizumab arm, respectively, achieved all composite endpoint component thresholds (treatment difference: 9.4%; 95% confidence interval: \u22123.0, 21.5). The composite endpoint provided a single and simultaneous measurement of overall benefit for patients receiving treatment for PNH. Use of the composite endpoint in future PNH research is recommended to determine clinical benefit, and its use in health technology assessments should be evaluated.<\/jats:p>","DOI":"10.1111\/ejh.13746","type":"journal-article","created":{"date-parts":[[2022,1,31]],"date-time":"2022-01-31T18:19:36Z","timestamp":1643653176000},"page":"391-402","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Composite endpoint to evaluate complement inhibition therapy in patients with paroxysmal nocturnal hemoglobinuria"],"prefix":"10.1111","volume":"108","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3180-3570","authenticated-orcid":false,"given":"Austin","family":"Kulasekararaj","sequence":"first","affiliation":[{"name":"King\u2019s College Hospital King\u2019s College London, and NIHR\/Wellcome Trust King\u2019s Clinical Research Facility  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2611-7656","authenticated-orcid":false,"given":"Axel","family":"Glasmacher","sequence":"additional","affiliation":[{"name":"AG Life Science Consulting  Alfter Germany"},{"name":"Department of Medicine III University of Bonn  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8596-847X","authenticated-orcid":false,"given":"Peng","family":"Liu","sequence":"additional","affiliation":[{"name":"Alexion Pharmaceuticals, Inc.  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