Efficacy and safety profile of xanthines in COPD: a network meta-analysis

Background: Theophylline can still have a role in the management of stable COPD but its use remains controversial mainly due to its narrow therapeutic window. Doxofylline, another xanthine, is an effective bronchodilator and displays a better safety profile with respect to theophylline. Aim: We have carry out a quantitative synthesis to compare the efficacy and safety profile of different xanthines in COPD. Methods: A network meta-analysis on xanthines (aminophylline, bamiphylline, doxofylline, enprophylline, theophylline) and COPD was carried out in agreement with PRISMA and PROSPERO. The primary endpoints were the impact of xanthines on the lung function and the risk of adverse events (AEs), via normalizing data on safety as a function of person-week. Data obtained from 1158 COPD patients were selected from 16 studies and analyzed by using a full Bayesian approach. Results: The combined surface under the cumulative ranking curve (SUCRA) analysis of efficacy (change from baseline in forced expiratory volume in 1 second [FEV1]) and safety (risk of AEs) showed that doxofylline was superior to aminophylline (comparable efficacy and significantly better safety), bamiphylline (significantly better efficacy and comparable safety), and theophylline (comparable efficacy and significantly better safety) (Figure 1). Conclusions: The overall efficacy/safety analysis suggests that doxofylline seems to be the best xanthine for the treatment of COPD.