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Evidence summaries

Inhaled Corticosteroids in COPD

Inhaled corticosteroids compared to placebo reduce the rate of exacerbations and the decline in quality of life in patients with chronic obstructive pulmonary disease but at the cost of increased adverse effects (oropharyngeal candidiasis, hoarseness, pneumonia). There is no effect on mortality and the effect on lung function appears to be modest at the most. Level of evidence: "A"

A Cochrane review [Abstract] 1 included 55 studies with a total of 16 154 subjects with stable chronic obstructive pulmonary disease (COPD). Long term use of ICS (> 6 months) did not consistently reduce the rate of decline in FEV1 (generic inverse variance analysis: MD 5.80 ml/year with ICS over placebo, 95% CI -0.28 to 11.88; 2 333 participants; pooled means analysis: 6.88 ml/year, 95% CI 1.80 to 11.96; 4 823 participants), although one major trial demonstrated a statistically significant difference. There was no statistically significant effect on mortality in COPD patients (OR 0.98, 95% CI 0.83 to 1.16; 8 390 participants). Long term use of ICS reduced the mean rate of exacerbations in those studies where pooling of data was possible (generic inverse variance analysis: MD -0.26 exacerbations per patient per year, 95% CI -0.37 to -0.14; 2 586 participants; pooled means analysis: MD -0.19 exacerbations per patient per year, 95% CI -0.30 to -0.08; 2253 participants). ICS slowed the rate of decline in quality of life, as measured by the St George's Respiratory Questionnaire (WMD -1.22 units/year, 95% CI -1.83 to -0.60, 2 507 participants). Response to ICS was not predicted by oral steroid response, bronchodilator reversibility or bronchial hyper-responsiveness in COPD patients. There was an increased risk of oropharyngeal candidiasis (OR 2.65, 95% CI 2.03 to 3.46; 5 586 participants) and hoarseness. In the long-term studies, the rate of pneumonia was increased in the ICS group compared to placebo, in studies that reported pneumonia as an adverse event (OR 1.56, 95% CI 1.30 to 1.86; 6235 participants). The long-term studies that measured bone effects generally showed no major effect on fractures and bone mineral density over three years.

Another Cochrane review [Abstract] 2 included 43 studies with a total of more than 30 000 subjects with COPD. There were 26 fluticasone studies (n = 21 247) and 17 budesonide studies (n = 10 150). Fluticasone increased non-fatal serious adverse pneumonia events (requiring hospital admission) (OR 1.78, 95% CI 1.50 to 2.12; 18 more per 1000 treated over 18 months). Budesonide also increased non-fatal serious adverse pneumonia events compared with placebo, but the effect was less precise and was based on shorter trials (OR 1.62, 95% CI 1.00 to 2.62; 6 more per 1000 treated over 9 months). No significant difference in overall mortality rates was observed between either of the inhaled steroids and the control interventions, and pneumonia-related deaths were too rare to permit conclusions to be drawn.

A meta-analysis 3 included 11 randomized controlled trials with a total of 14 426 participants. In trials with mortality data, no difference was observed in 1-year all-cause mortality (128 deaths /4 636 patients in the treatment group, 148 deaths / 4 597 patients in the control group; RR 0.86; 95% 95% CI 0.68 to 1.09). ICS therapy was associated with a significantly higher incidence of pneumonia (777 cases / 5 405 patients vs. 561 cases / 5 371 patients in the control group; RR 1.34; 95% CI 1.03 to 1.75).

A systematic review 4 including 9 RCTs with a total of 3 976 subjects was abstracted in DARE. The use of inhaled corticosteroids was associated with a 30% reduction in exacerbations (RR 0.70, 95% CI 0.58 to 0.84; 6 trials). Sensitivity analysis revealed no dose-response effect. If the patients received systematic steroids during the run-in phase, the difference between the groups was not significant (RR 0.77, 95% CI 0.56 to 1.09). There was no significant difference between groups in all-cause mortality (RR 0.84, 95% CI 0.60 to 1.18; 5 trials). Concerning FEV1 (9 trials), the results were variable. Only 2 trials found a statistically significant difference between the groups. Oropharyngeal candidiasis (RR 2.1, 95% CI 1.5 to 3.1) and skin bruising (RR 2.1, 95% CI 1.6 to 2.8) were more common in patients treated with corticosteroids.

A systematic review 5 including 6 studies with a total of 3 571 subjects was abstracted in DARE. Treatment with inhaled corticosteroids produced no statistically significant effect on decline in FEV1 over time: the WMD was -5.0 ml/year (95% CI -11.2 to +1.2; 6 RCTs).

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    References

    • Yang IA, Clarke MS, Sim EH et al. Inhaled corticosteroids for stable chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2012;(7):CD002991. [PubMed].
    • Kew KM, Seniukovich A. Inhaled steroids and risk of pneumonia for chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2014;(3):CD010115. [PubMed]
    • Drummond MB, Dasenbrook EC, Pitz MW, Murphy DJ, Fan E. Inhaled corticosteroids in patients with stable chronic obstructive pulmonary disease: a systematic review and meta-analysis. JAMA 2008 Nov 26;300(20):2407-16. [PubMed]
    • Alsaeedi A, Sin DD, McAlister FA. The effects of inhaled corticosteroids in chronic obstructive pulmonary disease: a systematic review of randomized placebo-controlled trials. Am J Med 2002 Jul;113(1):59-65. [PubMed] [DARE]
    • Highland KB, Strange C, Heffner JE. Long-term effects of inhaled corticosteroids on FEV1 in patients with chronic obstructive pulmonary disease. A meta-analysis. Ann Intern Med 2003 Jun 17;138(12):969-73. [PubMed] [DARE]

Primary/Secondary Keywords