AUSTIN, Texas — Withdrawing inhaled corticosteroids (ICS) from patients with severe chronic obstructive pulmonary disease (COPD) did not lead to an increased rate of exacerbations, investigators reported.
Steroid withdrawal was associated with 1,097 exacerbations of any severity among 1,242 patients, which met statistical criteria for noninferiority versus continuation of ICS (1,078 exacerbations in 1,243 patients). The frequency of severe or moderate/severe exacerbations did not differ between groups or within any subgroups. The time to first COPD exacerbation also was similar between groups.
Withdrawal of ICS was associated with a larger drop in FEV1 during the final step of withdrawal, Helgo Magnussen, MD, of the Pulmonary Research Institute in Grosshansdorf, Germany, said here atCHEST 2014.
“In patients with GOLD [Global Initiative for Chronic Obstructive Lung Disease] 3-4 COPD, receiving dual bronchodilators, the risk for moderate to severe exacerbations is statistically noninferior with ICS withdrawal compared with ICS therapy,” Magnussen said. “On the basis of these results we conclude that inhaled corticosteroids may be successfully withdrawn in patients receiving dual bronchodilator therapy with a long-acting muscarinic antagonist (LAMA) and a long-acting beta-agonist (LABA).”
In contrast, hospitalized patients with severe COPD had an increased risk of subsequent hospitalization for pneumonia if they did not receive prophylactic antibiotic therapy, according to results of a separate study reported at the meeting.
Previous studies have shown that LAMA-ICS combination therapy reduces the risk of exacerbations in severe COPD as compared with monotherapy, Magnussen said by way of background. Additionally, dual bronchodilator therapy with a LAMA and a LABA has demonstrated superiority over either agent alone.
Magnussen and colleagues hypothesized that ICS could be withdrawn from patients receiving LAMA-LABA combination therapy without increasing the risk of moderate or severe COPD exacerbations compared with patients who continued ICS in addition to dual bronchodilator therapy.
To test the hypothesis, they randomized 2,485 patients with severe COPD (GOLD stage 3-4) managed with triple therapy to continue ICS along with dual bronchodilation or to a step-down steroid withdrawal strategy. The primary endpoint was the time to a first moderate or severe on-treatment exacerbation during 12 months of randomized therapy.
The trial had statistical power to demonstrate noninferiority, defined as hazard ratio of <1.2. Noninferiority was tested in the overall study population and in prespecified subgroups stratified by geographic region, age, sex, smoking status, baseline body mass index, and COPD treatment history.
The treatment groups did not differ significantly with respect to baseline characteristics, including a mean age of 64 and a mean FEV1 of 0.98 L.
The primary analysis yielded an HR of 1.058 for ICS withdrawal versus continuation. Subgroup analysis did not identify any patients who fared significantly better or worse with ICS withdrawal. A stratified analysis by baseline FEV1 also showed no difference between groups, nor did analyses of time to first moderate exacerbation, first severe exacerbation, or first exacerbation of any severity.
Magnussen noted that the ICS withdrawal group had similar lung function during the first 12 weeks of follow-up, followed by a 39 mL decline at week 18, increasing to 43 mL at week 52. In contrast, FEV1 remained stable throughout the 12-month study in patients who continued ICS.
Hospitalization for Pneumonia in COPD Patients Increases if They Did Not Receive Antibiotic Therapy During Hospitalization for COPD Exacerbation
Patients in an evaluation of another form of less intensive therapy for COPD did not fare as well as in the ICS trial. Specifically, patients hospitalized for an acute exacerbation of COPD had double the rate of pneumonia-related hospitalization in the next year if they did not receive antibiotic therapy during hospitalization for the COPD exacerbation, reported Luis Felipe Reyes, MD, of the University of Texas Health Science Center at San Antonio.
Investigators retrospectively reviewed records of 1,421 patients admitted to 12 British hospitals during 2009-2011 for acute exacerbations of COPD. The primary objective was to determine the translation of clinical data into clinical practice: Previous studies had shown that increased sputum purulence was the only Anthonisen (Article Removed) criterion that predicted clinical failure in outpatients with mild or moderate COPD not treated with antibiotics. Use of a point-of-care test for C-reactive protein further increased the predictive accuracy of treatment failure, Reyes said.
The records showed that 259 (18%) of the 1,421 hospitalized patients did not receive antibiotics during hospitalization for COPD exacerbation. The only significant difference between patients who did and did not receive antibiotics was a higher proportion of Anthonisen type 3 (mild) exacerbations in the latter group (31% versus 19%, P<0.001).
After correcting for Anthonisen severity criteria, the investigators found that patients who did not receive antibiotics during hospitalization for COPD exacerbation had an odds ratio of 2.04 for pneumonia-related hospitalization in the 12 months after discharge (13.5% versus 7.7%, P=0.001).
“Understanding antibiotic selection and initiation in patients hospitalized for acute exacerbations of COPD may predict the need for subsequent hospitalization of COPD patients,” Reyes said.
The study by Magnussen’s group was supported by Boehringer Ingelheim who is the manufacturer of Anoro which is a LABA/LAMA combination. This makes me worry about this study.
Magnussen disclosed relevant relationships with Boehringer Ingelheim, Berlin-Chemie, Almirall, AstraZeneca, Chiesi, Novartis, Takeda , AB2BIO, Bayer, and InterMune.
Reyes disclosed no relevant relationships with industry.