The use of long-term continuous cyclic azithromycin (LT-CC-A) therapy in patients with severe chronic obstructive pulmonary disease (COPD) was associated with sustained reductions in exacerbations and hospitalization rates with few adverse events, according to the results of a recent retrospective cohort analysis conducted at the Respiratory Day Care Unit of Sabadell Hospital in Barcelona, Spain, and published in Chest.
The primary outcome of the study was whether the efficacy of LT-CC-A treatment is maintained beyond the first year of therapy by comparing the first, second, and third year of CC-A therapy with the 12-month period prior to the treatment. COPD exacerbations, hospitalizations for respiratory disease, and length of hospital stays were all main outcomes. The effect of treatment on the bacteriology of bronchial secretions was also studied. A secondary study outcome was the assessment of patients treated with CC-A for <24 months, defined as short-term CC-A (ST-CC-A) therapy. One azithromycin 500-mg tablet was administered 3 times per week (Monday, Wednesday, and Friday).
A cohort of 505 participants with severe COPD (per Global Initiative for Obstructive Lung Disease stage D [GOLD D]) served as both control and treatment arms between January 2007 and December 2013. A total of 109 patients with severe COPD and ≥4 COPD exacerbations in the previous year comprised the main target population of this study. Overall, 64.2% (70 of 109) of the participants comprised the ST-CC-A group and 35.8% (39 of 109) comprised the LT-CC-A group.
In the 39 study participants, a total of 236 COPD exacerbations occurred in the 12 months before beginning LT-CC-A therapy, of which 52.1% (123 of 236) were severe and warranted hospitalization (total 857 days of hospital stay). In the LT-CC-A group, average reductions in COPD exacerbations at baseline were 56.2% at 12 months, 70% at 24 months, and 41% at 36 months. Reductions in hospitalization were 62.6%, 75.8%, and 39.8% at 12 months, 24 months, and 36 months, respectively. COPD exacerbations linked to common microorganisms decreased by 12.5% and 17.3% at 12 months and 24 months, respectively, after LT-CC-A therapy, with a 50% increase in macrolide resistance. In addition, at 12 months and 24 months, rates of COPD exacerbations caused by Pseudomonas aeruginosa increased by 7.2% and 13.1%, respectively.
CC-A therapy was well tolerated, with few adverse events reported. The most common adverse events were digestive disorders (7.1% in the ST-CC-A group) and hearing loss (5.1% in the LT-CC-A group).
The investigators concluded that the results of the current study support the use of LT-CC-A therapy in patients with COPD GOLD D who, even when receiving maximal medical therapy, close clinical care, and bacterial monitoring for 1 year continued to experience ≥4 moderate to severe COPD exacerbations each year. They emphasized, however, that use of this treatment requires careful clinical and microbiologic follow-up, with the possible occurrence of COPD exacerbations resulting from P aeruginosa and macrolide resistance taken into account.
Pomares X, Montón C, Bullich M, et al. Clinical and safety outcomes of long-term azithromycin therapy in severe COPD beyond the first year of treatment [published online February 7, 2018]. Chest. doi:10.1016/j.chest.2018.01.044