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.

Keywords:

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

Acknowledgements

Funding, medications and investigator’s meeting costs for this study were provided by Edmond Pharma. Funding information for this article has been deposited with the Crossref Funder Registry. Medical writing assistance was provided by Deirdre Elmhirst of Elmhirst Scientific Consultancy Limited, funded by Edmond Pharma. The authors do not plan to share further data beyond that included in this paper. We wish to acknowledge the substantial contribution of our late colleague Dr Edoardo Pozzi who died soon after this paper was submitted. His drive and commitment were crucial to ensuring that this project was completed. This paper was presented at the European Respiratory Society 2018 as a poster presentation with interim findings. The poster’s abstract was published in “Poster Abstracts” in the European Respiratory Journal https://erj.ersjournals.com/content/52/suppl_62/PA776

Author Contributions

All authors contributed to data analysis, drafting or revising the article, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Disclosure

EP is employed by Edmond Pharma. PC, CP, RDN, GF, MC, and AC report personal fees from Edmond Pharma. The authors report no other conflicts of interest in this work.