Comparative Effectiveness of Roflumilast and Azithromycin for the Treatment of Chronic Obstructive Pulmonary Disease

Jenny Lam; Ivy Tonnu-Mihara; Nicholas J Kenyon; Brooks T Kuhn

doi:10.15326/jcopdf.2021.0224

Comparative Effectiveness of Roflumilast and Azithromycin for the Treatment of Chronic Obstructive Pulmonary Disease

Chronic Obstr Pulm Dis. 2021 Oct 28;8(4):450-463. doi: 10.15326/jcopdf.2021.0224.

Authors

Jenny Lam^{1

2}, Ivy Tonnu-Mihara³, Nicholas J Kenyon^{4

5}, Brooks T Kuhn^{4

5}

Affiliations

¹ Department of Pharmaceutical and Health Economics, School of Pharmacy, University of Southern California, Los Angeles, California, United States.
² Leonard D. Schaeffer Center for Health Policy and Economics, University of Southern California, Los Angeles, California, United States.
³ Veterans Affairs Long Beach Healthcare System, Long Beach, California, United States.
⁴ Division of Pulmonary and Critical Care Medicine, School of Medicine, University of California, Davis, Sacramento, California, United States.
⁵ Veterans Affairs Northern California Healthcare System, Mather, California, United States.

Abstract

Background: In chronic obstructive pulmonary disease (COPD) patients with exacerbations despite optimized bronchodilator therapy, roflumilast and chronic azithromycin are recommended options. Roflumilast is recommended in severe COPD patients with chronic bronchitis, whereas chronic azithromycin is more broadly indicated. The comparative effectiveness between these 2 treatments to reduce exacerbation rate remains unclear.

Objectives: Our objective was analysis of the Veterans Health Administration (VHA) database (medication and claims data without lung function or presence of chronic bronchitis or tobacco use) to compare the effectiveness of roflumilast and azithromycin on hospitalizations and mortality.

Methods: The primary outcome of the study was cumulative incidences of first COPD-related and all-cause hospitalization. Sensitivity analysis on hospitalizations was conducted for VHA patients who also had Medicare.

Results: In 1302 roflumilast and 2573 azithromycin patients, the all-cause mortality rates at 1 year were 19% and 15%, respectively. The median times-to-all-cause death were 47 months (interquartile range [IQR] 16-81) for the roflumilast and 48 months (IQR 20-83) for the azithromycin groups. Roflumilast was associated with higher mortality (hazard ratio [HR] 1.16; 95% confidence interval [CI], 1.04-1.29). Roflumilast showed no significant association for COPD-related hospitalization (subdistribution HR [SHR]=1.14, 95% CI, 1.00-1.29) and all-cause hospitalization (HR 1.07, 95% CI, 0.97-1.18). For patients with Medicare (N=2030), roflumilast was associated with higher COPD-related (SHR 1.21; 95% CI, 1.05-1.41) and all-cause (SHR 1.23; 95% CI, 1.09-1.38) hospitalizations.

Conclusions: Roflumilast was associated with higher hazard ratios for death, COPD-related hospitalizations, and all-cause hospitalizations in COPD patients only after adjustment for VHA and external Medicare events. Prospective clinical trials are needed to directly compare the relative efficacy of these therapies.

Keywords: COPD exacerbation; azithromycin; roflumilast.

Abstract

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