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

Cazzola, Mario; Calzetta, Luigino; Barnes, Peter J.; Criner, Gerard J.; Martínez, Fernando J.; Papi, Alberto; Matera, Maria Gabriella

doi:10.1183/16000617.0010-2018

Cited by 45 publications

(27 citation statements)

References 53 publications

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“…Specifically, the numerator represents the count of total events and the denominator represents the given time duration multiplied by the number of patients [22]. Such a method has been supported by the Cochrane Collaboration and successfully used in recent meta-analyses [20, 21, 23, 24].…”

Section: Methodsmentioning

confidence: 99%

Efficacy and safety profile of mucolytic/antioxidant agents in chronic obstructive pulmonary disease: a comparative analysis across erdosteine, carbocysteine, and N-acetylcysteine

et al. 2019

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Background To date there are no head-to-head studies comparing different mucolytic/antioxidant agents. Considering the inconsistent evidence resulting from the pivotal studies on mucolytic/antioxidant agents tested in chronic obstructive pulmonary disease (COPD), and the recent publication of Reducing Exacerbations and Symptoms by Treatment with ORal Erdosteine in COPD (RESTORE) study, we have performed a meta-analysis to compare the efficacy and safety of erdosteine 600 mg/day, carbocysteine 1500 mg/day, and N-acetylcysteine (NAC) 1200 mg/day in COPD. Methods A pairwise and network meta-analyses were performed to assess the efficacy of erdosteine, carbocysteine, and NAC on acute exacerbation of COPD (AECOPD), duration of AECOPD, and hospitalization. The frequency of adverse events (AEs) was also investigated. Results Data obtained from 2753 COPD patients were extracted from 7 RCTs published between 2004 and 2017. In the pairwise meta-analysis mucolytic/antioxidant agents significantly reduced the risk of AECOPD (RR 0.74 95%CI 0.68–0.80). The network meta-analysis provided the following rank of effectiveness: erdosteine>carbocysteine>NAC. Only erdosteine reduced the risk of experiencing at least one AECOPD ( P < 0.01) and the risk of hospitalization due to AECOPD ( P < 0.05). Erdosteine and NAC both significantly reduced the duration of AECOPD (P < 0.01). The AEs induced by erdosteine, carbocysteine, and NAC were mild in severity and generally well tolerated. The quality of evidence of this quantitative synthesis is moderate. Conclusions The overall efficacy/safety profile of erdosteine is superior to that of both carbocysteine and NAC. Future head-to-head studies performed on the same COPD populations are needed to definitely confirm the results of this meta-analysis. Trial registration CRD42016053762 .

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Section: Methodsmentioning

confidence: 99%

Efficacy and safety profile of mucolytic/antioxidant agents in chronic obstructive pulmonary disease: a comparative analysis across erdosteine, carbocysteine, and N-acetylcysteine

et al. 2019

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“…Pharmacological trials where the statistical significance matches clinical provide the greatest probability that the investigated treatment will be effective in clinical practice . Interestingly, the concept of MCID has been only recently investigated in meta‐analyses in human respiratory medicine . The MID based on change in R L can be used in pharmacological trials to identify responder asthmatic horses to a bronchodilator agent and this approach will permit deep analyses of results beyond the usual comparison of groups .…”

Section: Discussionmentioning

confidence: 99%

Clinical efficacy of bronchodilators in equine asthma: Looking for minimal important difference

Calzetta

Crupi

Roncada

et al. 2019

Equine Veterinary Journal

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Summary Background Airway obstruction is the main trait of severe equine asthma that affects respiratory function and elicits detrimental effects on clinical presentation. Only few and underpowered clinical studies have investigated the impact of improvement in lung function induced by bronchodilators on the clinical signs of asthma‐affected horses. Objectives To identify the minimal important difference (MID) in lung function elicited by bronchodilator leading to a meaningful improvement in clinical signs. Study design Pairwise meta‐analysis and meta‐regression analysis. Methods Literature searches were performed for studies that investigated the effect of bronchodilator therapy on lung function and clinical condition of asthmatic horses. The relationship between the change in lung function variables and clinical score was analysed via random‐effect meta‐regression. One‐point change of the Improved clinically Detectable Equine Asthma Scoring System (IDEASS) score was used to identify the MID. Results A significant (P<0.05) relationship was found between the changes in IDEASS score and maximum change in transpulmonary pressure (ΔPplmax) or pulmonary resistance (RL). Since only the model resulting for RL passed through the origin (Y‐intercept when X = 0: −0.31, 95% CI −0.75 to 0.14), this variable was used to identify the MID correlated with a meaningful improvement in clinical signs. The resulting MID value was a change in RL of 0.63 cm H2O/L/s (95% CI 0.33–0.94), representing the slope of meta‐regression model (high quality of evidence). Main limitations No long‐term studies investigated the effect of bronchodilator agents on both lung function and clinical signs in asthmatic horses. Conclusions In conclusion, bronchodilator pharmacotherapy in equine asthma elicits clinically meaningful effect when RL increases ≥1 cm H2O/L/s, a value indicating the MID. Assessing the MID based on change in RL may improve the quality of evidence and the scientific impact of future clinical trials as it extends beyond the simple, and limiting, evaluation of statistical significance.

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“…Notwithstanding the above-mentioned limitations, this pairwise meta-analysis suggests that in patients with COPD doxofylline acts as a bronchodilator drug having a wider therapeutic window than theophylline. These characteristics, along with its well-described anti-inflammatory [48] and steroid sparing effects [49] suggest that when a xanthine is indicated [50], doxofylline should be considered as an alternative to theophylline in the treatment of patients with COPD.…”

Section: Discussionmentioning

confidence: 99%