Long-acting beta-agonists offer benefits in COPD. Not true for inhaled corticosteroids for most, it turns out.
It once seemed as though treating COPD with inhaled corticosteroids (ICS) was the best thing since sliced bread. With ICS, COPD patients with an FEV1 of less than 50% of predicted seemed to experience a decrease in exacerbations as well as the time to their first exacerbation.1 Caution was urged, however, particularly regarding the increased risk of pneumonia with ICS use.
Later, the benefits of ICS were disproven.
Where are we now regarding ICS in the treatment of COPD? A recent article does a solid evidence-based job of answering that question.2
The authors express their critique up front. They identify 6 limitations to previous studies, which suggested that ICS decrease exacerbations of COPD.
• Most trials did not follow subjects for exacerbation outcomes after drug discontinuation.
• Loss of follow-up in general in these studies was frequent.
• The definition for an “exacerbation” was variable.
• Group differences may have been exaggerated by ICS withdrawal in placebo and long-acting beta-agonist (LABA) groups.
• Numbers needed to treat were incorrectly calculated.
• Adjustments for heterogeneity in regard to the number of exacerbations between patients were incorrect.
Later studies such as TORCH corrected some of the methodological problems.3 Treatment of COPD with ICS and LABA combination therapy was targeted. The study demonstrated that “ICS do not reduce mortality in patients with COPD.”2 There were 4 treatment groups in the TORCH study: placebo, fluticasone, salmeterol, and salmeterol/fluticasone. Furthermore, the study concluded that a statistically significant survival advantage was attained with LABA-but NOT with ICS!
Revisiting the critical clinical question of pneumonia risk with ICS also revealed sobering data. There was an overall 70% increase in pneumonia leading to hospitalization in persons with COPD using ICS. The most prohibitive risk occurred in those who inhaled more than 1000 µg/d of fluticasone.4
Is the book closed on the risks/benefits of ICS?
The answer is a qualified no. Some patients with COPD might actually benefit from ICS.2 If those individuals with COPD who have sputum-serum eosinophilia could be efficiently identified (and studied in randomized controlled trials), this group-as in individuals who have asthma-may derive benefits. Other characteristics of this “ICS-benefit group” might include those with2:
• A history of asthma
• A less than 20 pack-year history of smoking
• Less severe disease (FEV1 of more than 50% of predicted), and an FEV1 bronchodilator response of more than 12%.
The bottom line
There are benefits derived from use of LABA in the setting of COPD. Not so for ICS. There are also serious consequences when ICS are used-especially the increased risk of severe pneumonia. For now, a gradual withdrawal of ICS in this target cohort is warranted. Another study has shown that this is the safe way to go.5
1. Burge PS, Calverley PM, Jones PW, et al. Randomized, double blind, placebo-controlled study of fluticasone proprionate in patients with moderate to severe chronic obstructive pulmonary disease: the ISOLDE Trial. BMJ. 2000;320:1297-1303.
2. Ernst P, Saad N, Suissa S. Inhaled corticosteroids in COPD: the clinical evidence. Eur Respir Soc. 2014. doi:10.1183/09031936.00128914.
3. Calverley PM, Anderson JA, Celli B, et al. Salmeterol and fluticasone proprionate and survival in chronic obstructive pulmonary disease. N Engl J Med. 2007;356:775-789.
4. Ernst P, Gonzalez AV, Brassard P, et al. Inhaled corticosteroid use in chronic obstructive pulmonary disease and the risk of hospitalization in pneumonia. Am J Respir Crit Care Med. 2007;176:162-166.
5. Magnussen H, Disse B, Rodriguez-Roisin R, et al. Withdrawal of inhaled glucocorticoids and exacerbations of COPD. N Engl J Med. 2014;371:1285-1294.