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Abstract
BackgroundOral 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.MethodsA 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.ResultsData 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.ConclusionsDoxofylline is an effective and safe methylxanthine for the treatment of asthma, with an efficacy/safety profile greater than that of theophylline.Trial registrationMeta-analysis registration: CRD42019119849.
Highlights
Oral methylxanthines are effective drugs for the treatment of chronic obstructive respiratory disorders
The “Patient problem” included subject affected by asthma; the “Intervention” regarded the administration of doxofylline and theophylline; the “Comparison” was performed with regard to placebo and across each active treatment; the “Outcomes” were the asthma events, adverse events (AEs), lung function expressed as forced expiratory volume in 1 s (FEV1), and use of salbutamol as rescue medication
Studies characteristics Data obtained from 696 asthmatic patients (44.68% treated with doxofylline, 31.62% treated with theophylline, and 23.71% treated with placebo) were selected from 4 randomized controlled trials (RCTs) published between 2015 and 2018 [8,9,10]
Summary
Oral methylxanthines are effective drugs for the treatment of chronic obstructive respiratory disorders. Nowadays large-scale quantitative synthesis comparing the efficacy and safety profile of doxofylline vs theophylline in the treatment of asthma is still lacking. We performed a quantitative synthesis to compare the efficacy/safety profile of doxofylline and theophylline in asthma. Oral methylxanthines are recognized effective drugs for the clinical management of patients suffering from chronic obstructive respiratory disorders. Rogliani et al Multidisciplinary Respiratory Medicine (2019) 14:25 has been reported in further smaller clinical trials and retrospective studies [9,10,11,12,13,14], to date large-scale quantitative synthesis comparing the efficacy and safety profile of doxofylline vs theophylline in the treatment of asthma is still lacking. We performed a pairwise and network meta-analysis to definitively clarify which of the two drugs should be prescribed when a methylxanthine is recommended in asthmatic patients
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