Luigino Calzetta, Nicola A. Hanania, Frank L. Dini, Marc F. Goldstein, William R. Fairweather, William W. Howard, Mario Cazzola

This pooled analysis of double-blind, randomized, placebo-controlled trials aimed to investigate the Impact of DOxofylline compaRed tO THEOphylline (DOROTHEO 1 and DOROTHEO 2 studies) on functional and clinical outcomes in asthma. Patients with asthma ≥16 years of age with (forced expiratory volume in 1 s [FEV1] ≥50% and <80% and with ≥15% post-bronchodilator increase in FEV1) were randomized in a 1:1:1:1 ratio in DOROTHEO 1 to receive doxofylline 200 mg, doxofylline 400 mg, theophylline 250 mg, or placebo; in DOROTHEO 2 patients were randomized in a 1:1:1 ratio to receive doxofylline 400 mg, theophylline 250 mg, or placebo. All double-blind treatments were taken orally with immediate release formulations and three times daily. Data evaluating the effect of doxofylline 400 mg, theophylline 250 mg and placebo on FEV1, asthma events rate, use of salbutamol as rescue medication and adverse events (AEs) were pooled from both studies. The pooled-analysis of 483 patients demonstrated that both doxofylline 400 mg and theophylline 250 mg significantly increased FEV1, reduced the rate of asthma events and use of salbutamol to relieve asthma symptoms compared to placebo (p < 0.01). No significant differences were detected between doxofylline 400 mg and theophylline 250 mg. Doxofylline 400 mg did not significantly (p > 0.05) increase the risk of AEs compared to placebo, conversely in patients treated with theophylline 250 mg the risk of AEs was significantly (p < 0.05) greater than in those that received placebo. We conclude that doxofylline seems to offer a promising alternative to theophylline with a superior efficacy/safety profile in the management of patients with asthma.