N-Acetylcysteine: An Alternative to ICS for Reducing COPD Exacerbations?

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The recently published post hoc analysis of the PANTHEON (Placebo-controlled study on efficAcy and safety of N-acetylcysTeine High dose in Exacerbations of chronic Obstructive pulmoNary disease) study reaffirmed the benefits of N-acetylcysteine (NAC) in cutting down the incidence of chronic pulmonary disease (COPD) exacerbations. The most important finding of the study was a significant reduction in exacerbation particularly in COPD patients with a substantial history of smoking, and amongst those not treated with inhaled corticosteroids (ICS). N-acetylcysteine might thus provide an alternative to ICS containing combinations in COPD patient, hinted the researchers.

The PANTHEON study has already established the efficacy and safety of twice daily NAC 600 mg in reducing the risk of exacerbations associated with moderate to severe COPD. Being one of the largest study, PANTHEON recruited ex- and never-smokers, concomitantly treated with other medications. A symptom-based definition of COPD exacerbations rather than the conventional healthcare resource utilization (HCU) criteria was used. The present study is a post-hoc analysis of the PANTHEON study that investigated the impact of smoking status or use of concomitant medications on the efficacy of NAC with regards to reduction in exacerbations (as per the HCU definition).

Overall, NAC (n=482) reduced the rate of HCU events by a significant 20% as against placebo (N=482) (p=0.0027).  Most exacerbations reported in the group were of moderate severity, for which there was a significant 18% reduction with NAC vs. placebo (p=0.0275).  NAC was associated with a significant 26% reduction in the incidence of mild exacerbations (p=0.0337). The incidence of severe exacerbations was rare in the study population. Although NAC reduced the incidence of severe exacerbation vs. placebo the difference was not significant.  The reduction in exacerbations with NAC vs. placebo in current/ex-smokers was similar to that of general population (23%; p<0.01).

Overall, NAC was most effective in patients not receiving ICS as background COPD medication. NAC treatment was associated with a significant 27% reduction in the rate of all exacerbations (i.e., mild, moderate and severe) vs. placebo in the ICS naïve subgroup as compared to a significant 49% reduction in patients who received one or more long-acting bronchodilator but without ICS. N-acetylcysteine rather than placebo was associated with a significant 57% reduction in COPC exacerbations when added to LABA without ICS. The findings were similar for patients with moderate exacerbations.

A separate analysis was conducted for patients receiving NAC along with long-acting inhaled bronchodilator(s) without ICS vs. placebo plus long acting bronchodilator(s) with ICS. Patients in the former group experienced a 60% (p<0.0001) reduction in the rate of exacerbations as against the placebo group who received long-acting bronchodilator(s) and ICS. Moreover, there was a significant 64% reduction in the rate of moderate exacerbations, and a significant 88% reduction in the incidence of severe exacerbations amongst patients receiving NAC along with long-acting inhaled bronchodilator(s) without ICS vs. those treated with placebo along with long-acting bronchodilator(s) and ICS.

Respir Med. 2019; 147: 37-43.