Drotrecogin alfa (activated): a pharmacoeconomic review of its use in severe sepsis

Drotrecogin alfa (activated) [Xigris] (DAA), the recombinant form of human activated protein C, is approved as an adjunctive therapy for patients with severe sepsis (sepsis associated with > or = 1 organ system failure [OSF]). In the international, randomised, double-blind, placebo-controlled PROWESS (Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis) study, the absolute reduction in 28-day all-cause mortality with intravenous DAA 24 micro g/kg/h for 96 hours plus conventional care versus conventional care alone was 6.1%. Although lacking statistical power, a prospectively planned subgroup analysis of this study suggested that the absolute reduction in mortality increased in patients with a baseline APACHE (Acute Physiology and Chronic Health Evaluation) II score of > or = 25 or > or = 2 OSFs, with no clear treatment effect in patients with an APACHE II score of < or = 24 or 1 OSF. Three fully published cost-effectiveness/cost-utility models of DAA plus conventional care relative to conventional care alone adopted a national healthcare payer's and/or societal perspective in North America. The base-case (baseline) discounted incremental cost per life-year gained (LYG) with DAA for all patients with severe sepsis was $US15,801-33,300 (year of costing 2000-2002). The results were more favourable for patients with an APACHE II score of > or = 25 ($US10,833-19,723 per LYG), but considerably worse for patients with an APACHE II score of < or = 24 based on a post hoc reanalysis by the US FDA. Among several fully or partly published cost-effectiveness/cost-utility models that adopted a national healthcare payer's perspective in continental Western European countries, the base-case (baseline) undiscounted incremental cost per LYG was broadly similar and more favourable for patients with > or = 2 OSFs (9660-11,300 euros; year of costing/publication 1998/1999, 2000, 2002 or 2003) than for all patients with severe sepsis (13,436-15,071 euros) in those studies that reported both analyses. The DAA acquisition cost accounts for up to 95% of the additional cost of using the drug. In conclusion, DAA is a major advance in the treatment of severe sepsis, based on the significant mortality reduction observed in the PROWESS study. From a hospital/hospital pharmacy perspective, the drug is associated with a high acquisition cost and a small increase in other short-term costs. From a societal or national healthcare payer's perspective, however, its administration to patients who meet the PROWESS study inclusion criteria, especially individuals with more severe disease (e.g APACHE II score of > or =25 and/or > or = 2 OSFs), has a lifetime cost-effectiveness profile that compares well to that of many widely accepted therapies.