Disease-modifying treatments in paroxysmal nocturnal hemoglobinuria: a systematic review of economic evaluations

Paroxysmal Nocturnal Hemoglobinuria (PNH) is a rare, life-threatening hematologic disorder characterized by chronic hemolysis, bone marrow and organ failure, and thrombotic events. Without effective treatment, PNH can lead to severe complications, including organ damage, increased morbidity, and heightened mortality risk. The high expense and therapeutic revolution that has emerged in PNH necessitates a careful appraisal of its cost-effectiveness. This study aimed to systematically review the cost-effectiveness of disease-modifying therapies (DMTs) in PNH. A comprehensive search syntax was developed to identify relevant studies using online databases. Criteria used in health economic evaluations include costs, effectiveness assessment with life-years gained (LYG) or quality-adjusted life-years (QALY), incremental cost-effectiveness ratio (ICER), and other clinico-economic outcomes. To enable comparison across different countries, the results of economic evaluations allow for the comparison of costs and ICERs across all studies, which were converted into United States Dollars (USD) values using the time model developed. The quality of the studies was assessed using the Quality of Health Economic Studies (QHES) instrument. This study is conducted and reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Nine papers were included in the 351 screened records. Pegcetacoplan was a dominant (i.e., less costly and more effective) option compared to C5 complement inhibitors and iptacopan. Eculizumab was not cost-effective compared with other DMTs or the standard of care. The current annual price of $12,300-$13,100 for adding danicopan to ravulizumab was not cost-effective compared to ravulizumab alone. The results of nine studies indicated that the majority of costs are related to the DMTs themselves. The cost-effectiveness analyses of DMTs in PNH suggest that the newer options, pegcetacoplan and iptacopan, are cost-effective and provide greater clinical utility than complement C5 inhibitors, especially eculizumab.