Doxycycline Added to Prednisolone in Outpatient-Treated Acute Exacerbations of COPD: A Cost-Effectiveness Analysis Alongside a Randomised Controlled Trial

Abstract

Background Most patients with mild to severe chronic obstructive pulmonary disease (COPD) experience exacerbations, which are also associated with increased healthcare costs. Despite limited evidence of antibiotics' benefits for exacerbations in outpatients, antibiotics are frequently prescribed. The aim of this study was to investigate whether doxycycline added to prednisolone is cost-effective compared to placebo plus prednisolone for the treatment of COPD acute exacerbations. Methods An economic evaluation from the societal perspective was performed alongside a 2-year randomised trial in 301 COPD patients in the Netherlands. The primary outcome was cost per quality-adjusted life year (QALY). The secondary outcome was cost per exacerbation prevented. Healthcare utilisation and loss of productivity were measured using retrospective questionnaires and clinical report forms. Missing data were imputed using multiple imputations by chained equations. Bootstrapping was employed to estimate statistical uncertainty surrounding cost-effectiveness outcomes. A sensitivity analysis from the healthcare perspective was performed. Results On average, costs in the doxycycline group were €898 higher than in the placebo group [95% confidence interval (CI) − 2617 to 4409] for the 2 years of follow-up. QALY values were higher in the doxycycline group (0.03; 95% CI − 0.00 to 0.06), but patients in this group suffered 0.01 more exacerbations than patients in the placebo group (95% CI − 0.14 to 0.11). Cost-effectiveness acceptability curves showed that the probability of doxycycline being cost-effective compared to placebo was 61% and 43% at a willingness-to-pay threshold of €34,000 per QALY and per exacerbation avoided, respectively. The sensitivity analysis showed similar results from the healthcare system perspective. Conclusions In patients with mild to severe COPD treated for exacerbations in an outpatient setting, doxycycline added to prednisolone is not cost-effective compared to prednisolone plus placebo over a 2-year period. Aureliano Paolo Finch and Patricia van Velzen equally contributed to this work.