AUSTIN, TEX. – Inhaled corticosteroids can be successfully withdrawn without increasing the risk of exacerbations in patients who have chronic obstructive pulmonary disease and are receiving dual bronchodilator therapy with a long-acting muscarinic antagonist (LAMA) and a long-acting beta2-agonist (LABA), according to findings from the WISDOM study.
However, inhaled corticosteroid (ICS) withdrawal should be conducted with caution, as a small but statistically significantly greater decrease in lung function occurred in patients who withdrew completely, compared with those who did not during the 12-month, double-blind, parallel-group study, Dr. Helgo Magnussen reported at the annual meeting of the American College of Chest Physicians.
“In patients with severe but stable COPD who are receiving combination therapy with tiotropium, salmeterol and ICS, a stepwise withdrawal of ICS was noninferior to continuation of ICS with respect to the risk of moderate or severe exacerbations. Despite this, if you do [withdraw ICS] – and we believe you can try to withdraw ICS – please observe the symptoms and lung function, because we found this signal [for decreased lung function],” he said.
Study subjects were 2,485 adults over age 40 years with severe or very severe COPD and a history of exacerbations. All patients received triple therapy with the LAMA tiotropium at 18 mcg four times daily, the LABA salmeterol at 50 mcg twice daily, and the ICS fluticasone at 500 mcg twice daily for a 6-week run-in period.
The patients were randomized to continue the triple therapy or to undergo ICS withdrawal over 12 weeks, with a dose reduction every 6 weeks.
ICS withdrawal met the prespecified noninferiority criterion of 1.20 for the upper limit of the 95% confidence interval, compared with continued ICS with respect to moderate or severe COPD exacerbation (hazard ratio, 1.06), but the adjusted mean reduction from baseline in the trough forced expiratory volume in 1 second (FEV1) at week 18 was 38 mL greater in the ICS withdrawal group, said Dr. Magnussen of the Pulmonary Research Institute at Lung Clinic Grosshansdorf (Germany), Airway Research Center North.
A similar between-group difference of 43 mL was seen at week 52, he said, noting that this did not differ significantly from the difference seen at week 18, demonstrating that there is no further decline in lung function after complete ICS withdrawal at week 18.
Also, the decline in lung function – even at the peak decrease in function at week 18, was not associated with an increase in dyspnea; the difference in change from baseline in the modified Medical Research Council (mMRC) dyspnea scale was nonsignificant for ICS withdrawal, compared with ICS continuation at week 18 or week 52. The change from baseline in the St. George’s Respiratory Questionnaire (SGRQ) total score was 0.55 with ICS withdrawal, compared with –0.42 with ICS at week 27, and 1.15, compared with –0.07 for withdrawal vs. continuation, respectively, at week 52. This difference, though statistically significant, was not considered clinically relevant, Dr. Magnussen said.
ICS treatment is recommended along with long-acting bronchodilators in patients with frequent exacerbations of severe COPD, but the benefits of ICS use in addition to dual bronchodilator therapy have not been fully elucidated, he said.
The findings of the WISDOM study (N. Engl. J. Med. 2014;371:1285-94), suggest that ICS discontinuation is possible.This study was funded by Boehringer Ingelheim. Dr. Magnussen reported receiving consultant fees and/or serving on a speakers bureau or advisory committee for Almirall, Boehringer Ingelheim, Chiesi, Berli-Chemi, and Novartis. His employer, the Pulmonary Research Institute, received payments for conducting the study.