Bone Marrow Failure Disorders

In this international multicenter study reported in the Journal of Haematology, researchers developed and evaluated a novel composite endpoint to assess complement inhibition treatment impact (using data from ravulizumab PNH Study 301; ClinicalTrials.gov Identifier: NCT02946463) on patients with paroxysmal nocturnal hemoglobinuria (PNH) who met 5 expert-selected composite endpoint variables — lactate dehydrogenase (LDH) 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; and transfusion avoidance. Complete terminal complement inhibition and a reduction in LDH levels were achieved by all patients in the ravulizumab arm of the study. All 5 composite endpoint component thresholds were achieved in 51.2% of patients in the ravulizumab arm and in 41.3% of patients in the eculizumab study arm (treatment difference: 9.4%; 95% CI, –3.0 to 21.5). The investigators concluded, "The composite endpoint provided a single and simultaneous measurement of overall benefit for patients receiving treatment for PNH." They recommended its use in future PNH research, "to determine clinical benefit," and its evaluation as a tool in health technology assessments.