Risk-to-benefit ratio of inhaled corticosteroids in patients with COPD

Abstract

While the pharmacological management of chronic obstructive pulmonary disease (COPD) has evolved from the drugs used to treat asthma, the treatment models are different and the two diseases require clear differential diagnosis in order to determine the correct therapeutic strategy. In contrast to the almost universal requirement for anti-inflammatory treatment of persistent asthma, the efficacy of inhaled corticosteroids (ICS) is less well established in COPD and their role in treatment is limited. There is some evidence of a preventive effect of ICS on exacerbations in patients with COPD, but there is little evidence for an effect on mortality or lung function decline. As a result, treatment guidelines recommend the use of ICS in patients with severe or very severe disease (forced expiratory volume in 1 second <50% predicted) and repeated exacerbations. Patients with frequent exacerbations - a phenotype that is stable over time - are likely to be less common among those with moderate COPD (many of whom are managed in primary care) than in those with more severe disease. The indiscriminate use of ICS in COPD may expose patients to an unnecessary increase in the risk of side-effects such as pneumonia, osteoporosis, diabetes and cataracts, while wasting healthcare spending and potentially diverting attention from other more appropriate forms of management such as pulmonary rehabilitation and maximal bronchodilator use. Physicians should carefully weigh the likely benefits of ICS use against the potential risk of side-effects and costs in individual patients with COPD.

Conflict of interest statement

DP has consultant arrangements with Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Merck, Mundipharma, Novartis, Pfizer, Sandoz and Teva. He or his research team has received grants and support for research in respiratory disease from the following organisations in the last 5 years: UK National Health Service, Aerocrine, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Merck, Mundipharma, Novartis, Nycomed, Pfizer and Teva. He has spoken for Almirral, AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, GlaxoSmithKline, Kyorin, Merck, Mundipharma, Pfizer and Teva. He has shares in AKL Ltd which produces phytopharmaceuticals. He is the sole owner of Research in Real Life Ltd. Within the past 36 months BY has received research funding for studies in COPD from BI-Pfizer, Novartis, Merck and has served on the COPD advisory board for future phase 4 studies for BI-Pfizer and Novartis. She has also received funding from NHLBI and ATS related to spirometry use for COPD in primary care practice. GB has, within the last 5 years, received honoraria for lectures from AstraZeneca, Boehringer-Ingelheim, Chiesi, GlaxoSmithKline, MerckSharp&Dohme, Novartis, Pfizer, and UCB. He is a member of advisory boards for AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, and Novartis. AR has received reimbursement for attending symposia, fees for speaking, fees for organising education, funds for research, and fees for consulting from AstraZeneca, Boehringer/Pfizer, Chiesi, GlaxoSmithKline, Novartis, and Nycomed/Tanaka.

Figures

Figure 1

Effect of treatment on the annual rate of exacerbations in the TORCH Study. ***p<0.001 vs. placebo, *p<0.05 vs. placebo. RR = rate ratio. Data from Calverley et al.

Figure 2

Effect of treatment on probability of 3-year mortality. Data from the TORCH Study.

Figure 3

Adjusted rate ratios of hospitalisation for pneumonia associated with current use, past use, and dose of inhaled corticosteroid (ICS). All doses were converted to fluticasone equivalents and categorised as high (fluticasone ≥1,000μg/day), moderate (fluticasone 500–999μg/day), and low (fluticasone et al.

Figure 4

Risk of fractures with increasing dose of inhaled corticosteroid: results from observational studies included in a meta-analysis. Reproduced from Loke et al. with permission