TY - JOUR
T1 - Withdrawal of Inhaled Glucocorticoids and Exacerbations of COPD
AU - Magnussen, H.
AU - Disse, B.
AU - Rodriguez-Roisin, R.
AU - Kirsten, A.
AU - Watz, H.
AU - Tetzlaff, K.
AU - Towse, L.
AU - Finnigan, H.
AU - Dahl, R.
AU - Decramer, M.
AU - Chanez, P.
AU - Wouters, E.F.M.
AU - WISDOM Investigators, the
AU - Calverley, P.M.A.
PY - 2014/10/2
Y1 - 2014/10/2
N2 - BACKGROUNDTreatment with inhaled glucocorticoids in combination with long-acting bronchodilators is recommended in patients with frequent exacerbations of severe chronic obstructive pulmonary disease (COPD). However, the benefit of inhaled glucocorticoids in addition to two long-acting bronchodilators has not been fully explored.METHODSIn this 12-month, double-blind, parallel-group study, 2485 patients with a history of exacerbation of COPD received triple therapy consisting of tiotropium (at a dose of 18 mu g once daily), salmeterol (50 mu g twice daily), and the inhaled glucocorticoid fluticasone propionate (500 mu g twice daily) during a 6-week run-in period. Patients were then randomly assigned to continued triple therapy or withdrawal of fluticasone in three steps over a 12-week period. The primary end point was the time to the first moderate or severe COPD exacerbation. Spirometric findings, health status, and dyspnea were also monitored.RESULTSAs compared with continued glucocorticoid use, glucocorticoid withdrawal met the prespecified noninferiority criterion of 1.20 for the upper limit of the 95% confidence interval (CI) with respect to the first moderate or severe COPD exacerbation (hazard ratio, 1.06; 95% CI, 0.94 to 1.19). At week 18, when glucocorticoid withdrawal was complete, the adjusted mean reduction from baseline in the trough forced expiratory volume in 1 second was 38 ml greater in the glucocorticoid-withdrawal group than in the glucocorticoid-continuation group (PCONCLUSIONSIn patients with severe COPD receiving tiotropium plus salmeterol, the risk of moderate or severe exacerbations was similar among those who discontinued inhaled glucocorticoids and those who continued glucocorticoid therapy. However, there was a greater decrease in lung function during the final step of glucocorticoid withdrawal. (Funded by Boehringer Ingelheim Pharma; WISDOM ClinicalTrials.gov number, NCT00975195.)
AB - BACKGROUNDTreatment with inhaled glucocorticoids in combination with long-acting bronchodilators is recommended in patients with frequent exacerbations of severe chronic obstructive pulmonary disease (COPD). However, the benefit of inhaled glucocorticoids in addition to two long-acting bronchodilators has not been fully explored.METHODSIn this 12-month, double-blind, parallel-group study, 2485 patients with a history of exacerbation of COPD received triple therapy consisting of tiotropium (at a dose of 18 mu g once daily), salmeterol (50 mu g twice daily), and the inhaled glucocorticoid fluticasone propionate (500 mu g twice daily) during a 6-week run-in period. Patients were then randomly assigned to continued triple therapy or withdrawal of fluticasone in three steps over a 12-week period. The primary end point was the time to the first moderate or severe COPD exacerbation. Spirometric findings, health status, and dyspnea were also monitored.RESULTSAs compared with continued glucocorticoid use, glucocorticoid withdrawal met the prespecified noninferiority criterion of 1.20 for the upper limit of the 95% confidence interval (CI) with respect to the first moderate or severe COPD exacerbation (hazard ratio, 1.06; 95% CI, 0.94 to 1.19). At week 18, when glucocorticoid withdrawal was complete, the adjusted mean reduction from baseline in the trough forced expiratory volume in 1 second was 38 ml greater in the glucocorticoid-withdrawal group than in the glucocorticoid-continuation group (PCONCLUSIONSIn patients with severe COPD receiving tiotropium plus salmeterol, the risk of moderate or severe exacerbations was similar among those who discontinued inhaled glucocorticoids and those who continued glucocorticoid therapy. However, there was a greater decrease in lung function during the final step of glucocorticoid withdrawal. (Funded by Boehringer Ingelheim Pharma; WISDOM ClinicalTrials.gov number, NCT00975195.)
KW - OBSTRUCTIVE PULMONARY-DISEASE
KW - RANDOMIZED CONTROLLED-TRIAL
KW - FLUTICASONE PROPIONATE
KW - CORTICOSTEROIDS
KW - PREVENTION
KW - TIOTROPIUM
KW - SALMETEROL
KW - ISOLDE
U2 - 10.1056/NEJMoa1407154
DO - 10.1056/NEJMoa1407154
M3 - Article
C2 - 25196117
SN - 0028-4793
VL - 371
SP - 1285
EP - 1294
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 14
ER -