OBJECTIVES: Paroxysmal nocturnal haemoglobinuria (PNH) is an ultra-orphan disease characterized by intravascular haemolysis and venous thrombosis. This systematic literature review (SLR) assesses model-based economic evaluations of C5 inhibitors, used to manage PNH.

METHODS: MEDLINE^® In-Process was systematically searched, using Preferred Reporting Items for Systemic Reviews and Meta-Analyses (PRISMA) guidelines, by pairing relevant keywords to identify studies taking a formal decision-analytic modelling approach. Electronic searches were supplemented by bibliographic searches.

RESULTS: Of the 156 publications, a study each conducted in the US, UK, Canada and Brazil met the inclusion criteria. Cost–utility analysis was conducted using a Markov model in Canada, Brazil and the US; the UK model performed a preliminary cost-effectiveness analysis based on clinical evidence. A US payer and Brazilian public health perspective was adopted in the respective studies; the economic perspective was not reported in the remaining two. Three studies assessed eculizumab versus standard of care (SoC) or placebo, while one study assessed ravulizumab versus eculizumab. In Canada, the incremental cost per life year gained was CAN$4.62 million, and CAN$2.13 million per quality-adjusted life year (QALY) for eculizumab over SoC. In Brazil, the incremental cost-effectiveness ratio (ICER) for eculizumab versus SoC was R$10,139,542.84 per QALY. Opportunity cost of eculizumab per patient funded was 102.3 discounted QALYs. A US comparison between ravulizumab and eculizumab favoured ravulizumab in terms of health benefits and cost savings (ICER: -US$1,000,818).

CONCLUSIONS: This SLR suggests eculizumab may provide substantial benefits in terms of life expectancy, but at higher incremental costs, impacting its cost‑effectiveness. Ravulizumab proved to be a dominant strategy versus eculizuamab, resulting in large cost saving and increased benefits. However, results should be interpreted with caution due to paucity of economic modelling in PNH, and heterogeneity in populations considered in the current models. Further, exploring more cost-effective treatment options is warranted in future.