Efficacy and safety profile of doxofylline compared to theophylline in asthma: a meta-analysis

Abstract

Background: Oral methylxanthines are effective drugs for the treatment of chronic obstructive respiratory disorders. The novel methylxanthine doxofylline, that has bronchodilator and anti-inflammatory activities, is not affected by the major drawback of theophylline. Nowadays large-scale quantitative synthesis comparing the efficacy and safety profile of doxofylline vs. theophylline in the treatment of asthma is still lacking. Therefore, we performed a quantitative synthesis to compare the efficacy/safety profile of doxofylline and theophylline in asthma. Methods: A pairwise and network meta-analyses were performed to assess the impact of doxofylline vs. theophylline and placebo on the change in asthma events, risk of adverse events (AEs), forced expiratory volume in 1 s (FEV1), and salbutamol use. Results: Data obtained from 696 asthmatic patients were extracted from 4 randomized controlled trials published between 2015 and 2018. Doxofylline was significantly (P < 0.05) more effective than theophylline in reducing the daily asthma events (mean difference − 0.14, 95%CI -0.27 – 0.00) and risk of AEs (relative risk 0.76, 95%CI 0.59–0.99). Doxofylline was as effective as theophylline in improving FEV1, and a trend of superiority (P = 0.058) was detected for doxofylline over theophylline with respect to the reduction in the use of salbutamol as rescue medication. The rank of effectiveness was doxofylline>theophylline> > placebo, and the rank of safety was placebo>doxofylline> > theophylline. Conclusions: Doxofylline is an effective and safe methylxanthine for the treatment of asthma, with an efficacy/ safety profile greater than that of theophylline. Trial registration: Meta-analysis registration: CRD42019119849.

The Impact of Corticosteroids on Human Airway Smooth Muscle Contractility and Airway Hyperresponsiveness: A Systematic Review

“…Another important point arising from this systematic review is that ICS can be ineffective in preventing AHR in smoking patients with asthma, a condition related to the presence of relative steroid resistance due to the impairment of histone deacetylase 2 (HDAC2) [ 28 , 46 ]. In these smoking asthmatics, perhaps adding drugs that are able to restore HDAC2 activity such as doxofylline may help support the therapeutic effect of ICS [ 47 , 48 , 49 , 50 , 51 ].…”