Objective: To assess the cost-effectiveness of rhDNase (Pulmozyme(R)) for patients with cystic fibrosis (CF) aged 5 years or more, with mild to moderate lung disease. The review addresses four questions: a) does rhDNase therapy work in the short term?, b) does rhDNase therapy work more effectively in certain groups of patients?, c) does rhDNase therapy work in the long term? and d) what is the cost-effectiveness of rhDNase therapy?
Methods: A structured rapid review with modelling and cost-effectiveness calculations. Electronic searches were carried out to identify randomised controlled trials (RCTs), systematic reviews, epidemiological and economic information. Databases searched included Cochrane Library, Medline, Healthstar, Embase, PreMedline and NHS Economic Evaluation Database (NHS EED). Exclusion criteria were trials of very short duration (14 days or less) and those which looked at CF patients with severe lung disease. Open label extensions providing information on longer term outcomes were included.
Results: Nine published RCTs were identified, although only one met the inclusion criteria. This large RCT was of good methodological quality, and shows that treatment with rhDNase over a 6-month period improves lung function, and decreases the risk of respiratory exacerbations. Expert opinion suggests that there are identifiable subgroups of patients showing improvement, little or no change, and deterioration after treatment with rhDNase. However, the best supporting evidence for this comes from a retrospective case series, showing that response to rhDNase is highly variable, and that early improvement was a good predictive marker for long-term benefit. Evidence for the long-term impact of rhDNase is not yet available from any RCTs. A simplified model was therefore developed to estimate the decline in lung function for patients treated with rhDNase, compared with those who were not treated. From this model it appears that the continued use of rhDNase over the lifetime of a CF patient might extend their life expectancy by 2 years. If treatment is limited to a subgroup of patients with moderate lung disease who respond to treatment, the continued use of rhDNase might extend their life expectancy by 7 years. Using the model, the discounted cost per life year gained for all patients is estimated at approximately pound52 500, with a range of between approximately pound25 000-57 000 from sensitivity analysis. For the subgroup of patients, the discounted cost per life year gained is estimated at approximately pound16 000, with a range of between approximately pound18 000-36 600 from sensitivity analysis.
Conclusions: Although there is short-term evidence that the use of rhDNase improves lung function and decreases the risk of respiratory exacerbations, at present there is no evidence from RCTs to indicate whether this effect is sustained over a longer time period, or whether rhDNase is associated with a reduction in mortality. RCTs to date have been of insufficient duration to answer important questions about long term outcomes, particularly the effects of rhDNase on lung function, respiratory exacerbations and mortality. Further long-term research is needed, with economic analysis to evaluate the long term cost-effectiveness of rhDNase. Research is also needed to identify, in advance, which patients would benefit most from this expensive treatment.