Pharmacology and Clinical Efficacy of Erdosteine in Chronic Obstructive Pulmonary Disease

Maurizio Moretti

Disclosures

Expert Rev Resp Med. 2007;1(3):307-316. 

In This Article

Clinical Efficacy

The clinical efficacy of erdosteine has been evaluated in more than 30 clinical studies involving patients with COPD and CB with acute exacerbation or who are clinically stable. Clinical trials have compared the efficacy of erdosteine with placebo and other treatments, including other mucolytic agents ( Table 1 ).

Erdosteine has been shown to improve the outcome of acute exacerbations of CB and COPD in several comparative studies. An international, multicenter, prospective, double-blind, parallel-group clinical trial was conducted in acute exacerbation of COPD (European Chronic Obstructive Bronchitis Erdosteine Study [ECOBES]).[29] A total of 237 patients with acute exacerbations were randomized into two comparable groups to receive, for a minimum of 7 to a maximum of 10 days, either amoxycillin 500 mg three-times daily plus erdosteine (300 mg twice daily) or amoxycillin 500 mg three-times daily plus placebo. The primary efficacy end point was the global clinical assessment (GCA), a cumulative index of six different measurements, including sputum parameters (appearance and viscosity) and functional signs (difficulty to expectorate, rhonchi at auscultation, cough and dyspnea intensity). These parameters were measured at admission, after 3–4 days and at the end of treatment (7–10 days), and were scored using a four-point graded scale. The final score was expressed as a value obtained from the addition of the various scores for these parameters. Clinical symptoms improved significantly in the group receiving erdosteine and amoxycillin compared with the group receiving amoxycillin alone, as indicated by the GCA score, with an earlier improvement in the group receiving erdosteine. In fact, after 7–10 days, sputum viscosity, sputum appearance and functional signs of COPD improved with erdosteine plus amoxycillin, with a significant difference from days 3–4 up to day 10.

Similar results were reported in another multicenter, randomized, double-blind clinical trial versus placebo during exacerbation of COPD.[31] The study compared two groups treated with ciprofloxacin at the dose of 500 mg twice daily plus placebo and ciprofloxacin 500 mg twice daily plus erdosteine 300 mg twice daily. The erdosteine group demonstrated a significant and faster improvement of clinical symptoms compared with the group receiving ciprofloxacin alone. The efficacy of erdosteine has been compared with that of other mucolytic agents and was shown to be at least similar (but often consistently higher). Two studies were undertaken to examine the efficacy and tolerability of erdosteine versus ambroxol in patients with acute exacerbation of CB receiving concomitant antibiotic therapy.[38,39] Patients receiving erdosteine had a faster and significant reduction in the severity and frequency of cough compared with the group receiving ambroxol, and also experienced a faster and more consistent decrease of sputum viscosity and/or volume. Similar to erdosteine, NAC contains a sulfhydryl group responsible for its pharmacological activity. NAC is a mucolytic agent with antioxidant activities through its direct antioxidant properties and indirect role as a precursor in glutathione synthesis.[40]

Two studies have compared the efficacy and safety profile of erdosteine and NAC used in combination with antibiotics in acute exacerbation of COPD. Both treatments produced a significant improvement in all clinical parameters when compared with baseline. In one study, conducted in 195 patients with COPD and bronchial infection, the extent of improvement from baseline was similar for the two treatments; however, a forced expiratory volume in 1 s (FEV1) increase of 14% from baseline was observed in the patients treated with erdosteine and not in those treated with NAC.[41] In the second study, erdosteine showed a significantly faster onset of effect compared with NAC on sputum volume, sputum viscosity and cough frequency.[42] Erdosteine also showed a better tolerance compared with NAC, in terms of adverse gastrointestinal side effects.

The efficacy of erdosteine in the treatment of clinically stable COPD was evaluated in two crossover, double-blind, placebo-controlled studies.[27,43] In both studies, short treatment (<12 weeks) with erdosteine 300 mg twice daily improved clinical parameters, assessed according to a scoring scale, compared with the placebo group.

Two long-term trials showed that erdosteine treatment was able to decrease the incidence of acute exacerbations in patients with stable COPD.[44,45] The Erdosteine on Quality of Life (EQUALIFE) study, a double-blind, multicenter study enrolled 155 COPD patients (80% males) treated with erdosteine 600 mg/day or placebo for up to 8 months, in addition to the usual therapies.[45] The main objectives were to assess the number of exacerbations, the number and duration of hospitalizations, quality of life and the overall disease-related costs compared with placebo. The study enrolled patients with moderate-to-severe COPD defined by the Global Initiative for Obstructive Lung Disease (GOLD) diagnostic criteria[46] with mean FEV1% pred. of 59.4 and 59.0 in the erdosteine and placebo group, respectively. A total of 30% of the patients received inhaled steroids plus bronchodilators in the two study groups.

In the group of patients treated with erdosteine, a statistically significant reduction of exacerbations, hospitalizations and number of days in hospital was observed; moreover, a significant improvement of the quality of life was obtained compared with placebo. In fact, over the 8 months of the study patients treated with erdosteine had 30% fewer exacerbations and 58% fewer days in hospital than patients with placebo. Erdosteine improved and maintained the health-related quality of life, assessed using both generic (Short Form-36) and disease-specific (St George's Respiratory Questionnaire) questionnaires. Finally, the overall disease-related costs were lower in the erdosteine group. Safety was excellent, with the incidence of adverse events not different between erdosteine and placebo.

A recent post hoc analysis of the EQUALIFE study showed the positive effects of adding erdosteine into routine bronchodilator therapy in moderate and severe COPD patients. The addition of erdosteine on the top of combination therapy of inhaled steroids and bronchodilators significantly reduced the exacerbation and hospitalization rates compared with the group receiving the routine inhalation treatment alone,[47] suggesting that adding erdosteine to inhaled steroids could lead to a relevant advantage in terms of antioxidant/anti-inflammatory effects, as indicated previously by the synergistic activity observed in vitro.[21]

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