PMID- 31133026 OWN - NLM STAT- MEDLINE DCOM- 20191223 LR - 20200225 IS - 1465-993X (Electronic) IS - 1465-9921 (Print) IS - 1465-9921 (Linking) VI - 20 IP - 1 DP - 2019 May 27 TI - Efficacy and safety profile of mucolytic/antioxidant agents in chronic obstructive pulmonary disease: a comparative analysis across erdosteine, carbocysteine, and N-acetylcysteine. PG - 104 LID - 10.1186/s12931-019-1078-y [doi] LID - 104 AB - 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 . FAU - Rogliani, Paola AU - Rogliani P AUID- ORCID: 0000-0001-7801-5040 AD - Unit of Respiratory Medicine, Department of Experimental Medicine, University of Rome "Tor Vergata", Via Montpellier 1, 00133, Rome, Italy. paola.rogliani@uniroma2.it. FAU - Matera, Maria Gabriella AU - Matera MG AD - Unit of Pharmacology, Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy. FAU - Page, Clive AU - Page C AD - Sackler Institute of Pulmonary Pharmacology, Institute of Pharmaceutical Science, King's College London, London, UK. FAU - Puxeddu, Ermanno AU - Puxeddu E AD - Unit of Respiratory Medicine, Department of Experimental Medicine, University of Rome "Tor Vergata", Via Montpellier 1, 00133, Rome, Italy. FAU - Cazzola, Mario AU - Cazzola M AD - Unit of Respiratory Medicine, Department of Experimental Medicine, University of Rome "Tor Vergata", Via Montpellier 1, 00133, Rome, Italy. FAU - Calzetta, Luigino AU - Calzetta L AD - Unit of Respiratory Medicine, Department of Experimental Medicine, University of Rome "Tor Vergata", Via Montpellier 1, 00133, Rome, Italy. LA - eng GR - NA/Edmond Pharma Srl/ PT - Comparative Study PT - Journal Article PT - Meta-Analysis DEP - 20190527 PL - England TA - Respir Res JT - Respiratory research JID - 101090633 RN - 0 (Antioxidants) RN - 0 (Expectorants) RN - 0 (Thioglycolates) RN - 0 (Thiophenes) RN - 740J2QX53R (Carbocysteine) RN - 76J0853EKA (erdosteine) RN - WYQ7N0BPYC (Acetylcysteine) SB - IM MH - Acetylcysteine/adverse effects/*therapeutic use MH - Antioxidants/adverse effects/*therapeutic use MH - Carbocysteine/adverse effects/*therapeutic use MH - Expectorants/adverse effects/*therapeutic use MH - Humans MH - Pulmonary Disease, Chronic Obstructive/diagnosis/*drug therapy/epidemiology MH - Randomized Controlled Trials as Topic/methods MH - Thioglycolates/adverse effects/*therapeutic use MH - Thiophenes/adverse effects/*therapeutic use MH - Treatment Outcome PMC - PMC6537173 OTO - NOTNLM OT - COPD OT - Carbocysteine OT - Erdosteine OT - Meta-analysis OT - N-acetylcysteine COIS- 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. EDAT- 2019/05/28 06:00 MHDA- 2019/12/24 06:00 PMCR- 2019/05/27 CRDT- 2019/05/29 06:00 PHST- 2019/04/16 00:00 [received] PHST- 2019/05/20 00:00 [accepted] PHST- 2019/05/29 06:00 [entrez] PHST- 2019/05/28 06:00 [pubmed] PHST- 2019/12/24 06:00 [medline] PHST- 2019/05/27 00:00 [pmc-release] AID - 10.1186/s12931-019-1078-y [pii] AID - 1078 [pii] AID - 10.1186/s12931-019-1078-y [doi] PST - epublish SO - Respir Res. 2019 May 27;20(1):104. doi: 10.1186/s12931-019-1078-y.