Antibiotic therapy appears beneficial for patients with COPD

(Press-News.org) ATS 2013, PHILADELPHIA ─ Extended use of a common antibiotic may prolong the time between hospitalizations for patients suffering from chronic obstructive pulmonary disease (COPD), according to a post-hoc analysis of a multicenter study which compared the hospitalization rates of patients treated with a 12-month course of azithromycin to the rates of those treated with placebo.

The results of the current analysis will be presented at the ATS 2013 International Conference.

"Preventing respiratory-related re-hospitalizations is a key component of COPD therapy, and previous research has shown that a 12-month course of azithromycin decreases the risk of acute exacerbations of COPD," said lead author Fernando Martinez, MD, MS, director of pulmonary diagnostic services at the University of Michigan Health System. "COPD patients who have been hospitalized for a respiratory event are at particularly high risk for re-hospitalization, and we wanted to examine whether chronic azithromycin therapy might provide a benefit in these patients."

For their study, the researchers used clinical data gathered from a previous study of azithromycin use conducted by the COPD Clinical Research Network (CCRN), a group of research centers established to study new treatments for COPD and funded by the National Heart, Lung, and Blood Institute (NHLBI). All patients who participated in the study either had experienced an acute exacerbation of COPD in the 12 months prior to study enrollment or had used supplemental oxygen at the time of enrollment. Patients were randomized to receive either a daily dose of 250 mg of azithromycin or placebo for one year. In response to a recent FDA report suggesting a link between azithromycin and cardiovascular events, Dr. Martinez emphasized that the study excluded individuals with a heart condition known as prolonged QTc and those at risk for the condition.

The researchers noted the time any patient had an initial respiratory-related hospitalization and then measured the time that elapsed before the same patient was re-hospitalized, keeping track of the total number of hospitalizations as well as those that were due to respiratory-related causes such as pneumonia, influenza, bronchitis, asthma or acute exacerbation of COPD.

Next, the researchers compared that elapsed time in patients treated with azithromycin with those receiving placebo, adjusting their comparison for differences in age, gender and health and lifestyle indicators, and found that patients treated with azithromycin had a longer period between their first respiratory related hospitalization and the next hospitalization compared to patients treated with placebo. Among those re-hospitalized, the study found that age, gender, inhaled medication regimens and respiration measurements were similar between patients treated with azithromycin and those who received placebo.

"When comparing patients treated with azithromycin and those who received placebo, we found that there was a significant delay from the first respiratory-related hospitalization to the next one among those treated with azithromycin," said Dr. Martinez, who is also a professor of internal medicine at the university. "Also, looking at re-hospitalization due to any cause, we found there was a trend toward a delay between first and subsequent all-cause hospitalizations for patients taking azithromycin compared to those that did not take it."

While these results suggest prolonged azithromycin therapy may offer significant benefits to COPD patients, Dr. Martinez cautions that right now, the results of the post-hoc analysis provide an interesting hypothesis but no clear answers with regard to therapeutic recommendations. Additional studies will be needed to confirm the results, he added.

### * Please note that numbers in this release may differ slightly from those in the abstract. Many of these investigations are ongoing; the release represents the most up-to-date data available at press time.

Abstract 40862 Chronic Azithromycin Therapy Decreases The Risk Of Re-Hospitalization In Patients With COPD
Type: Scientific Abstract
Category: 09.11 - COPD: Pharmacological Treatment (CP)
Authors: F.J. Martinez1, J. Connett2, H. Voelker2, G.J. Criner3, M.K. Han1, B.J. Make4, F.C. Sciurba5, D.E. Niewoehner6, P.G. Woodruff7, R.K. Albert8; 1University of Michigan - Ann Arbor, MI/US, 2University of Minnesota - Minneapolis, MN/US, 3Temple University Hospital - Philadelphia, PA/US, 4National Jewish Health - Denver, CO/US, 5University of Pittsburgh - Pittsburgh, PA/US, 6VM Medical Center - Minneapolis, MN/US, 7University of California, San Francisco - San Francisco, CA/US, 8Denver Health - Denver, CO/US; for the COPD CRN Investigators

Abstract Body Rationale: Azithromycin administration for one year decreases the risk of acute exacerbations of COPD (AECOPD), (N Engl J Med 2011; 365:689-98). Preventing respiratory related hospitalizations is a key component of COPD therapy. We hypothesized that chronic azithromycin therapy may provide benefit in COPD patients who have been hospitalized for a respiratory related event; these patients are at particularly high risk for a re-hospitalization.

Methods: Subjects participating in the chronic azithromycin study were included. Subjects had COPD and either a history of an AECOPD in the prior 12 months or used supplemental oxygen at enrollment; they were randomized to azithromycin 250 mg daily vs. placebo for one year. We performed post-hoc analyses of time to next respiratory hospitalization after a first respiratory related hospitalization (pneumonia/influenza, bronchitis, asthma, AECOPD) during active study participation, comparing azithromycin to placebo-treated subjects; analyses were adjusted for age, gender, FEV1 %pred, O2 use, active smoking, and other COPD therapy. Results: Azithromycin treated patients experienced 156 respiratory related hospitalizations compared with 200 in placebo patients (HR 0.82; 95% CI 0.64-1.07). Of subjects who experienced a respiratory re-hospitalization, azithromycin-treated subjects (n=31) exhibited a similar age (64 ± 9 vs. 65 ± 8)), FEV1 (35 ± 13 vs. 36 ± 15 % pred), gender distribution (58% vs. 71% males), and inhaled medication regimen compared to placebo subjects (n=49). There was a significant prolongation in the time to the next respiratory hospitalization following the first respiratory related hospitalization during the study in azithromycin compared to placebo treated subjects (Figure 1A) (HR 0.58, 95% CI 0.34, 0.99); this event prolongation appears after approximately 40 days post discharge. A trend was seen for prolongation to the next all cause hospitalization following the first respiratory related hospitalization during the study in azithro (n=45) compared to placebo (n=65) patients (HR 0.71, 95% CI 0.47, 1.06) (Figure 1B).

Conclusion: Chronic azithromycin therapy may prolong time from a respiratory related hospitalization to the next respiratory or all-cause hospitalization. Additional, prospectively collected data are required to confirm that chronic azithromycin therapy in the immediate post-discharge period from a respiratory related hospitalization may provide a therapeutic option to prolong the time to the next hospitalization. END