OBJECTIVES

Eculizumab and ravulizumab are the only approved treatments for intravascular haemolysis caused by uncontrolled complement system activation in patients with paroxysmal nocturnal haemoglobinuria (PNH). Ravulizumab, engineered from eculizumab, provides immediate, complete and sustained complement C5 inhibition for up to 8 weeks, reducing the risk of breakthrough haemolysis (BTH) related to incomplete C5 inhibition. Ravulizumab (q8w) achieved noninferiority compared with eculizumab (q2w) in two phase 3 studies. We developed a ravulizumab-versus-eculizumab cost-utility analysis (CUA) in German, adult outpatients with PNH.

METHODS

CUA development was based on ravulizumab-versus-eculizumab clinical study data, literature review and clinical expert input. Outcomes, modelled over a lifetime and based on two phase 3 studies and published literature, included: current/historical/no BTH (related to incomplete C5 inhibition or complement-amplifying conditions); eculizumab dosage; administration frequency; remission; and blood transfusions. Costs were considered for a German outpatient setting. At abstract submission, ravulizumab’s price remained confidential in Germany. Benefits consisted of patient health-related quality of life (HRQoL), estimated via mapping EORTC QLQ-C30 measures to the EQ-5D-3L (German preference weights). The modelled cohorts were: 1) eculizumab-naïve; 2) stable on eculizumab (labelled dosage); 3) stable on eculizumab (higher dosage).

RESULTS

In the base case, mean incremental quality-adjusted life years (QALYs) for ravulizumab-versus-eculizumab were 0.53; mean incremental costs were EUR(2019) –1,906,440, reflecting ravulizumab’s economic ‘dominance’ (higher QALYs, lower costs), maintained in 91.7% of Monte-Carlo simulations. Ravulizumab dominance was maintained across deterministic-sensitivity analyses, with variation in the level of cost savings driven by use of higher-than-labelled eculizumab dosing for management of BTH. HRQoL data reflected a meaningful utility benefit (0.05-0.07) of blood transfusion avoidance, which was more common with ravulizumab than eculizumab in clinical studies.

CONCLUSIONS

The model demonstrated that ravulizumab is cost-saving compared with eculizumab for managing German adult outpatients with PNH, and provides moderate HRQoL benefits by reducing treatment burden and alleviating BTH and blood transfusion requirements.