Inhaled Corticosteroids Beneficial for Serious COPD

CHAPEL HILL, N.C., May 30 ? Inhaled corticosteroids may be beneficial for patients with moderate-to-severe chronic obstructive pulmonary disease (COPD), but don't appear to help those only mildly affected, according to a meta-analysis.

Reviewing 13 randomized controlled trials involving a total of more than 5,600 patients with COPD, Gerald Gartlehner, M.D., M.P.H., and colleagues at the University of North Carolina here found that for people with more serious COPD, the use of inhaled corticosteroids resulted in about 33% fewer exacerbations, with acceptable side effects. But the drugs had no effect on overall mortality.

"Overall, the risk-benefit ratio appears to favor inhaled corticosteroid treatment in patients with moderate to severe COPD," they wrote in the May-June issue of Annals of Family Medicine. "Existing evidence does not indicate a treatment benefit for patients with mild COPD."

The Global Initiative for Chronic Obstructive Lung Disease recommends the use of inhaled corticosteroids for patients with COPD who have a documented spirometric response to the agents, and for those with moderate-to-severe COPD-as defined by a forced expiratory volume in 1 second (FEV₁) response < 80% predicted-who have repeated exacerbations requiring treatment with antibiotics or oral corticosteroids.

To determine whether the potential benefits of inhaled steroids outweighed the risks of adverse events such as cataracts, glaucoma, and osteoporosis, the authors performed a meta-analysis of major medical databases, winnowing 880 initial studies to 13 randomized, double-blind trials comparing an inhaled corticosteroid to placebo in patients with COPD.

They also looked at an additional 11 studies (most of case-control or cross-sectional design) that evaluated the safety of inhaled corticosteroids in patients with COPD or asthma.

Among 4,300 patients in 10 studies looking at exacerbation rates, patients with COPD who were treated with inhaled corticosteroids had significantly fewer exacerbations than those on placebo (relative risk 0.67; 95% confidence interval, 0.59-0.77) at a mean followup of 20.8 months.

The treatment effect occurred largely in patients with moderate-to-severe disease as defined by American Thoracic Society criteria (FEV₁ ?50% to < 80% predicted for moderate COPD, and < 80% predicted for severe COPD), the authors noted.

When they restricted their analysis to seven studies that looked only at patients with moderate-to-severe disease, they found that the relative risks were virtually identical to those seen in the larger analysis.

In contrast, pooled results of three studies looking at patients with mild COPD found no apparent benefit for inhaled corticosteroids (relative risk 0.92; 95% CI, 0.55-1.53).

The authors noted, however, that "the sample size of this analysis is small, and point estimates of both subgroup analyses are within each other's confidence intervals. Inferences about differences of treatment effects must [therefore] be made cautiously."

They also found that the use of inhaled corticosteroids had no significant effect on mortality, with the pooled relative risk for all-cause mortality in 4,370 patients being 0.81 (95% CI, 0.60-1.08).

"Overall, 2.9% of patients on placebo and 2.5% of patients on inhaled corticosteroids died (P = 0.27) during the mean follow-up period of 22.3 months," they wrote. "Limiting the analysis to studies of moderate to severe COPD yielded almost identical results (relative risk = 0.84; 95% CI, 0.61-1.15). No differences in mortality were apparent between groups taking newer and older inhaled corticosteroids."

When the investigators tried to assess whether inhaled corticosteroids could improve quality of life, functional capacity, and respiratory tract symptoms, they found that the evidence was mixed.

Adverse events-rhinitis, oral candidiasis, sore throat, bruising, hoarseness, headache, cough, bronchitis, and upper respiratory infection-occurred in less than 10% of patients in most studies, and there were no differences in discontinuation rates between active treatment and placebo groups.

"Observational evidence, however, indicates a dose-related risk of cataract and open-angle glaucoma. Severe adverse events, such as osteoporotic fractures, are rare; the clinical importance of the additional risk is questionable," Dr. Gartlehner and colleagues wrote.

They noted that the relatively short duration of the studies they evaluated (up to 40 months) and the small sample sizes make it hard to asses the effects of treatment on rare long-term outcomes such as deaths or rare but serious side effects.

"Additional large studies are needed that have the necessary power to address such health outcomes as mortality and quality of life. Results of the ongoing TORCH (Towards a Revolution in COPD Health) survival study may provide answers to some remaining questions," the authors wrote.

The TORCH trial is a three-year, multicenter trial randomizing approximately 6,200 patients with moderate to severe COPD to placebo, Flovent (fluticasone), Advair (fluticasone/salmeterol), or Serevent (salmeterol). The trial is slated to end this year.