Current issues of ACP Journal Club are published in Annals of Internal Medicine


Therapeutics

Fluticasone reduced the severity of exacerbations in patients with COPD

ACP J Club. 1998 Sep-Oct;129:45. doi:10.7326/ACPJC-1998-129-2-045


Source Citation

Paggiaro PL, Dahle R, Bakran I, et al. Multicentre randomised placebo-controlled trial of inhaled fluticasone propionate in patients with chronic obstructive pulmonary disease. Lancet. 1998 Mar 14;351:773-80.


Abstract

Question

In patients with chronic obstructive pulmonary disease (COPD), is treatment with fluticasone propionate effective and safe?

Design

6-month randomized, double-blind, placebo-controlled trial.

Setting

Hospital outpatient clinics in 13 European countries, New Zealand, and South Africa.

Patients

281 patients (mean age 63 y, 74% men) with chronic bronchitis who were current or former smokers with ≥ 10 pack-year smoking history; were likely to have an exacerbation during treatment; had ≥ 1 exacerbation that required a visit to a physician or hospital each year for the previous 3 years; and had a regular productive cough, with FEV1 35% to 90% of predicted volume, forced vital capacity ≤ 70% of FEV1, and reversibility in FEV1 ≤ 15% (or volume change < 200 mL) after inhalation of salbutamol, 400 µg or 800 µg. Exclusion criteria were abnormal chest radiographs; use of oral or depot steroids, inhaled steroids, > 500 µg daily, or antibiotics; hospital admission within the previous 4 weeks; or current use of fluticasone propionate. Follow-up was 84%.

Intervention

Patients were allocated to fluticasone propionate, 2 puffs of 250 mg twice daily (n = 142), or a matching placebo (n = 139) given through a metered-dose inhaler. Use of a spacer was optional.

Main outcome measure

Number of patients who had ≥ 1 exacerbation.

Main results

No difference existed between groups in the number of patients who had ≥ 1 exacerbation (P = 0.45) (Table). The study had > 95% power to detect a 25% difference in exacerbations. Of the patients who had ≥ 1 exacerbation, fewer patients in the fluticasone propionate group than in the placebo group had moderate or severe exacerbations (60% vs 86%, P < 0.001). The occurrence of adverse events did not differ between groups.

Conclusions

In patients with chronic obstructive pulmonary disease, fluticasone propionate and placebo led to a similar incidence of exacerbations and adverse events. However, fewer moderate or severe exacerbations occurred in the fluticasone propionate group.

Source of funding: Not stated.

For correspondence: Dr. J. Efthimiou, Respiratory Clinical Research, Glaxo Wellcome Research and Development, 891-995 Greenford Road, Greenford, Middlesex UB6 0HE, England, UK. FAX 44-181-423-4401.


Table. Fluticasone propionate vs placebo at 6 months in patients with chronic obstructive pulmonary disease*

Outcome Fluticasone Placebo RRR (95% CI) NNT
≥ 1 exacerbation 32% 37% 14% (-19 to 38) Not significant

*Abbreviations defined in Glossary; RRR, NNT, and CI calculated from data in article.


Commentary

A recent comprehensive review identified 12 randomized, placebo-controlled studies of inhaled corticosteroids in patients with COPD (1). Nine of these studies tested short-term therapy (≤ 12 wk), and only 1 showed an improvement in FEV1. The other 3 studies evaluated longer-term treatment (104 to 130 wk) (2-4). Kerstjens and colleagues (2) found very small (and nonsignificant) improvements in FEV1 (4.4%) and reduced bronchial reactivity to histamine; similiarly, Derenne (3) found only a slight improvement in FEV1 (1.44% vs 0.62% in controls). Renkema and colleagues (4) found only a nonsignificant trend toward slower decline in FEV1 (-30 mL/y vs -60 mL/y in the placebo group).

The study by Paggiaro and colleagues may therefore rank as the most positive study yet reported, and it serves to re-ignite some enthusiasm for the use of inhaled corticosteroids in nonasthmatic patients with COPD. The most impressive finding, I believe, is the reduction in modest and severe clinical exacerbations. Although pulmonary function showed a statistically significant improvement, the magnitude of change was modest and of uncertain clinical importance. Clinical end points may be more sensitive and relevant indicators of treatment efficacy than serial pulmonary function testing obtained on a fixed schedule.

Routine, long-term use of inhaled corticosteroids in patients with COPD is not yet justified, in view of the generally negative results of clinical trials and the potential for side effects, including cataracts and glaucoma (1). Physicians should watch for the results of 3 large ongoing trials that may offer more definitive conclusions: the Lung Health Study II, the European Respiratory Society Study on COPD, and the International Study of Obstructive Lung Disease.

Herbert P. Wiedemann, MD
Cleveland Clinic FoundationCleveland, Ohio, USA


References

1. Barnes PJ, Pedersen S, Busse WW. Efficacy and safety of inhaled corticosteroids. New developments. Am J Respir Crit Care Med. 1998;157(3 Pt 2):S1-53.

2. Kertstjens HA, Brand PL, Hughes MD, et al., for the Dutch Chronic Non-Specific Lung Disease Study Group. A comparison of bronchodilator therapy with or without inhaled corticosteroid therapy for obstructive airways disease. Dutch Chronic Non-Specific Lung Disease Study Group. N Engl J Med. 1992;327:1413-9.

3. Derenne J. Effect of high dose inhaled beclomethasone on the rate of decline in FEV1 in patients with chronic obstructive pulmonary disease: results of a 2-year multicentre study. Am J Respir Crit Care Med. 1995;151:A463.

4. Renkema TE, Schouten JP, Koeter GH, Postma DS. Effects of long-term treatment with corticosteroids in COPD. Chest. 1996;109:1156-62.