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

Abstract

Background:

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.

• Authors: Peter Ma Calverley, Clive Page, Roberto W Dal Negro, Giovanni Fontana, Mario Cazzola, Arrigo F Cicero, Edoardo Pozzi, Jadwiga A Wedzicha
• Journal: International journal of chronic obstructive pulmonary disease (Int J Chron Obstruct Pulmon Dis) Vol. 14 Pg. 2733-2744 ( 2019) ISSN: 1178-2005 [Electronic] New Zealand
• PMID: 31819405 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial)
• Copyright: © 2019 Calverley et al.

Chemical References

• Antioxidants
• Expectorants
• Thioglycolates
• Thiophenes
• erdosteine

Topics

• Adult
• Aged
• Aged, 80 and over
• Antioxidants (adverse effects, therapeutic use)
• Disease Progression
• Double-Blind Method
• Europe
• Expectorants (adverse effects, therapeutic use)
• Female
• Forced Expiratory Volume
• Humans
• Lung (drug effects, physiopathology)
• Male
• Middle Aged
• Pulmonary Disease, Chronic Obstructive (diagnosis, drug therapy, physiopathology)
• Recovery of Function
• Severity of Illness Index
• Thioglycolates (adverse effects, therapeutic use)
• Thiophenes (adverse effects, therapeutic use)
• Time Factors
• Treatment Outcome