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Comparative Study
. 2019 May 27;20(1):104.
doi: 10.1186/s12931-019-1078-y.

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

Paola Rogliani  1 , Maria Gabriella Matera  2 , Clive Page  3 , Ermanno Puxeddu  4 , Mario Cazzola  4 , Luigino Calzetta  4
Affiliations
Comparative Study

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

Paola Rogliani et al. Respir Res. .

Abstract

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 .

Keywords: COPD; Carbocysteine; Erdosteine; Meta-analysis; N-acetylcysteine.

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Conflict of interest statement

PR participated as a lecturer, speaker, and advisor in scientific meetings and courses under the sponsorship of Almirall, AstraZeneca, Biofutura, Boehringer Ingelheim, Chiesi Farmaceutici, GlaxoSmithKline, Menarini Group, Mundipharma, and Novartis. Her department was funded by Almirall, Boehringer Ingelheim, Novartis, Zambon and Chiesi Farmaceutici.

MGM has participated as a lecturer, speaker, and advisor in scientific meetings and courses under the sponsorship of Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi Farmaceutici, GlaxoSmithKline and Novartis, and has been a consultant to Chiesi Farmaceutici.

CP has acted as a Consultant for Recipharma, ImmunoRegulation, PrEP Biopharma, Ockham Biosciences and Eurodrug. CP also owns equity in Verona Pharma who are developing novel drugs for the treatment of respiratory diseases.

EP has no conflict of interest to declare.

MC has participated as a lecturer, speaker, and advisor in scientific meetings and courses under the sponsorship of Almirall, AstraZeneca, Biofutura, Boehringer Ingelheim, Chiesi Farmaceutici, GlaxoSmithKline, Menarini Group, Lallemand, Mundipharma, Novartis, Pfizer, Verona Pharma, and Zambon, and has been a consultant to ABC Farmaceutici, Recipharm, Chiesi Farmaceutici, Lallemand, Novartis, Verona Pharma, and Zambon. His department was funded by Almirall, Boehringer Ingelheim, Novartis, and Zambon.

LC has participated as advisor in scientific meetings under the sponsorship of Boehringer Ingelheim and Novartis, received non-financial support by AstraZeneca, received a research grant partially funded by Chiesi Farmaceutici, Boehringer Ingelheim, Novartis, and Almirall, and is or has been a consultant to ABC Farmaceutici, Recipharm, Zambon, Verona Pharma, and Ockham Biotech. His department was funded by Almirall, Boehringer Ingelheim, Novartis, Zambon and Chiesi Farmaceutici.

Figures

Fig. 1
Fig. 1
PRISMA flow diagram for the identification of studies included in the meta-analysis (a) and diagram displaying the network across the treatments; the links between nodes indicate the direct comparisons between pairs of treatments; the numbers shown along the link lines indicate the number of patients comparing pairs of treatments head-to-head (b)
Fig. 2
Fig. 2
Forest plot of pair-wise meta-analysis of primary endpoints: impact of the erdosteine, carbocysteine, and NAC on the risk of AECOPD vs. placebo (a); sensitivity analysis performed by excluding the studies that introduced significant heterogeneity in the overall effect estimate (b); publication bias assessment via funnel plot (c) and Egger’s test (d); ranking plot resulting from the network meta-analysis in which treatments were plotted on X-axis according to SUCRA (score of 1 being the most effective) and on Y-axis according to the rank of being the best treatment (score of 1 being the most effective) (e). #P < 0.1, *P < 0.05, **P < 0.01, and ***P < 0.001. AECOPD acute exacerbation of COPD, COPD chronic obstructive pulmonary disease, NA not available, NAC N-acetylcysteine, SND standard normal deviate, SUCRA surface under the cumulative ranking curve
Fig. 3
Fig. 3
Forest plot of pair-wise meta-analysis of secondary endpoints: impact of the erdosteine, carbocysteine, and NAC on the risk of experiencing at least one AECOPD (a), duration of AECOPD (b), and risk of hospitalization due to AECOPD (c), vs. placebo. *P < 0.05 and **P < 0.01. AECOPD: acute exacerbation of COPD; COPD: chronic obstructive pulmonary disease
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