Inhaled corticosteroids in COPD

Inhaled corticosteroids (ICS)

Preliminary general considerations

• in vitro evidence suggests that COPD-associated inflammation has limited responsiveness to corticosteroids
  • also, some drugs including beta2-agonists, theophylline or macrolides may partially facilitate corticosteroid sensitivity in COPD
  • data suggest that the dose-response relationships and long-term (> 3 years) safety of inhaled corticosteroids (ICS) in patients with COPD are unclear and require further investigation
  • both current and ex-smokers with COPD benefit from ICS use in terms of lung function and exacerbation rates, although the magnitude of the effect is lower in heavy or current smokers compared to light or ex-smokers

Summary evidence (1):

• ICS (alone)
  • most evidence of ICS (alone) in COPD found that regular treatment with ICS alone does not modify the long-term decline of FEV1 nor mortality in patients with COPD
    
• ICS in combination with long-acting bronchodilator therapy
  • in patients with moderate to very severe COPD and exacerbations, an ICS combined with a LABA is more effective than either component alone in improving lung function, health status and reducing exacerbations
  • however, clinical trials powered on all-cause mortality as the primary outcome failed to demonstrate a statistically significant effect of combination therapy on survival
  • TORCH study (TOwards a Revolution in Chronic obstructive pulmonary disease [COPD] Health)
    • randomised double-blind study in 6,112 patients with COPD
      • compared the effects of inhaled salmeterol plus fluticasone (50/500mcg) with placebo, salmeterol (50mcg) alone or fluticasone (500mcg) alone
    • primary outcome was death from any cause for the comparison between the combination regimen and placebo
      • after three years, the proportion of deaths in the combination treatment group was not statistically significantly lower than in the placebo group (12.6% vs. 15.2%, respectively; hazard ratio 0.83, 95%CI 0.68 to 1.00, P=0.052)
      • combination therapy did significantly reduce the annual rate of exacerbations but, importantly, not the rate of severe exacerbations requiring hospitalisation, compared with salmeterol
      • pneumonia occurred more frequently in the combination and fluticasone groups, than in the salmeterol and placebo groups (19% vs. 13%) - means that, for every 17 people treated for three years with an inhaler containing fluticasone, instead of salmeterol alone or placebo, one suffered pneumonia
• blood eosinophil count and use of ICS in COPD
  • evidence that blood eosinophil counts predict the magnitude of the effect of ICS (added on top of regular maintenance bronchodilator treatment) in preventing future exacerbations
    • is a continuous relationship between blood eosinophil counts and ICS effects; no and/or small effects are observed at lower eosinophil counts, with incrementally increasing effects observed at higher eosinophil counts
    • the threshold of a blood eosinophil count > 300 cells/muL identifies the top of the continuous relationship between eosinophils and ICS, and can be used to identify patients with the greatest likelihood of treatment benefit with ICS
    • therefore, blood eosinophil counts can help clinicians estimate the likelihood of a beneficial preventive response to the addition of ICS to regular bronchodilator treatment, and thus can be used as a biomarker in conjunction with clinical assessment when making decisions regarding ICS use

Reference:

• (1) Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2024. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease
• (2) Calverley PMA et al. Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. N Engl J Med 2007;356:775-89