Effect of Erdosteine on COPD Exacerbations in COPD Patients with Moderate Airflow Limitation

Abstract

Peter MA Calverley,1 Clive Page,2 Roberto W Dal Negro,3 Giovanni Fontana,4 Mario Cazzola,5 Arrigo F Cicero,6 Edoardo Pozzi7,†, Jadwiga A Wedzicha8 1Department of Medicine, Clinical Sciences Centre, University Hospital Aintree, Liverpool, UK; 2Faculty of Life Sciences and Medicine, King’s College, London, UK; 3Lung Unit, National Centre for Respiratory Pharmacoeconomics and Pharmacoepidemiology, Verona, Italy; 4Pulmonology Department, Cough Centre, Careggi University Hospital, Firenze, Italy; 5Department of Systems Medicine, Chair of Respiratory Medicine, University of Rome ‘Tor Vergata’, Rome, Italy; 6Medical and Surgical Department, University of Bologna, Bologna, Italy; 7Medical Affairs Department, Edmond Pharma, Paderno, Italy; 8Respiratory Division, National Heart And Lung Institute, Imperial College London, London, UK†Dr Pozzii passed away on 9th July, 2019Correspondence: Peter MA CalverleyDepartment of Medicine, University Hospital Aintree, Lower Lane, Liverpool, Merseyside, UKTel [phone]Fax [phone]Email [email protected]: The RESTORE study, a multi-national randomized, placebo-controlled study, showed that erdosteine – a muco-active antioxidant that modulates bacterial adhesiveness – reduced the rate and duration of exacerbations in moderate and severe COPD with a history of exacerbations. How much benefit patients with less severe disease experience when taking this drug remains unclear.Methods: This post hoc analysis of the 254 RESTORE participants with spirometrically-defined moderate COPD (post-bronchodilator forced expiratory volume in 1 second [FEV1] 50‒79% predicted) examined exacerbation rate and duration, time to first exacerbation, and exacerbation-free time. Data were analyzed using descriptive statistics and comparisons between treatment groups used Wilcoxon rank-sum tests, Mann–Whitney U-tests, or log rank tests.Results: Patients with moderate COPD received erdosteine 300 mg twice daily (n=126) or placebo (n=128) added to usual COPD therapy for 12 months. During this time, there were 53 exacerbations in the erdosteine group and 74 in the placebo group, with 42.1% and 57.8% of patients, respectively, experiencing an exacerbation. There was a 47% reduction in the mean exacerbation rate with erdosteine compared to placebo (0.27 vs 0.51 exacerbations per-patient per-year, respectively, P=0.003), and a 58.3% reduction in the mild exacerbation rate (0.23 vs 0.53 mild exacerbations per-patient per-year, P=0.001). Mean duration of exacerbations was 26% shorter in erdosteine-treated patients (9.1 vs 12.3 days for placebo, P=0.022), with significant reductions in the duration of mild and moderate-to-severe exacerbations. Mean time to first exacerbation was prolonged by 7.7% (182 days for erdosteine vs 169 days for placebo, P<0.001) and the mean exacerbation-free time was increased by 51 days (279 days for erdosteine vs 228 days for placebo; P<0.001).Conclusion: These results indicate that adding erdosteine to usual COPD maintenance therapy reduces the number of mild, and duration of all, exacerbations in patients with moderate COPD and a history of exacerbations.Keywords: antioxidant, anti-inflammatory, chronic obstructive pulmonary disease, erdosteine, COPD exacerbations

Keywords

• antioxidant
• anti-inflammatory
• chronic obstructive pulmonary disease
• erdosteine
• copd exacerbations