PracticeUpdate Conference Series: ERS 2018

AzithromycinMay Reduce Time to Treatment Failure inAcute Exacerbations of COPD Themacrolide antibiotic azithromycinmay significantly reduce treatment failure during the

period of highest risk in COPD. A zithromycin may significantly reduce treatment failure during the highest-risk period of chronic obstructive pulmonary disease (COPD) requiring hospitalization. These benefits are lost, however, 6 months after discon- tinuing azithromycin. This finding of the multicenter, randomized, double-blind, placebo-controlled Belgian trial with Azithromycin for acute COPD Exacerbations requiring hospitalization (BACE) was reported at ERS 2018. Kristina Vermeersch, MS, of Universitair Ziekenhuis in Leuven, Belgium, and col- leagues set out to investigate the effect of azithromycin initiated within 48 h of hos- pital admission for an acute exacerbation of COPD (500 mg daily for 3 days) and administered subsequently for 3 months (250 mg for 2 days). BACE was a randomized, placebo-con- trolled, multicenter trial in 500 patients with COPD to determine the effectiveness and safety of azithromycin therapy in the acute setting of COPD exacerbations requiring hospital admission. Though long-term use of azithromycin is proven effective to prevent exacerbations, inherent risks outweigh the benefits. By reducing the dose and duration of azithromycin treatment and restricting it to acute periods of highest risk for treat- ment failure, benefits may counterbalance potential side effects, which may result in a new treatment strategy for these acute events. Patients were followed for 9 months, including 6 months after withdrawal of azithromycin. Time-to-treatment failure within 3 months was evaluated as a novel primary endpoint. Clinical failure was defined as the com- posite of death, treatment intensification (additional dose of systemic steroids, a switch of antibiotics for respiratory rea- sons, or a new course of systemic steroids and/or antibiotics) and an escalation in hospital care for respiratory reasons

exacerbations, relapse is common. Some patients remain at high risk of recurrent episodes for several weeks after the initial event. Failure may be related to inadequate antibiotic efficacy, but even with effec- tive bacterial eradication, or in cases of noninfectious events, increased airway inflammation may persist for a prolonged period after discharge and will likely pro- mote recurrence. Epidemiological data confirm that risk of subsequent events peaks drastically dur- ing 90 days after discharge and increases with all subsequent hospital admissions. Disrupting the vicious cycle of a severe exacerbation leading to a subsequent one is therefore promising. Ms. Vermeersch explained that azithro- mycin prevents acute exacerbations of COPD but the optimal dose, treatment duration, and target population are yet to be defined. Ms. Vermeersch concluded that azithro- mycin may significantly reduce treatment failure during the highest-risk period of acute exacerbations of COPD requiring hospitalization. These benefits are lost, however, 6 months after the discontinua- tion of azithromycin. " Epidemiological data confirm that risk of subsequent events peaks drastically during 90 days after discharge and increases with all subsequent hospital admissions. "

(from ward to intensive care unit during an index event, or from home to ward or intensive care unit [new admission] after discharge). Overall, 301 patients with COPD were randomized 1:1 to azithromycin (n=147) or placebo (n=154) in addition to stand- ard treatment with corticosteroids and antibiotics. The rate of treatment failure at 3 months was 49% in the azithromycin arm and 60% in the placebo arm (HR 0.73; 95% CI 0.53–1.01; P = .053 for time to treatment failure and change of –0.24; 95% CI –0.48 to 0.00; P = .040 for cumulative treatment failure). Treatment intensification, readmission for respiratory reasons, and mortality within 3 months were 47% versus 60% (P = .027), 13% versus 28% (P = .002), and 2% versus 4% (P = .507), respectively. Significance was lost 6 months after withdrawal of azithromycin. Though available treatments for COPD reduce the frequency of exacerbations by approximately 20% to 30%, these ther- apies are insufficient as many patients still experience at least one exacerbation a year. One-quarter of these exacerbations require hospitalization. A 2013 large European audit on COPD exacerbations in hospitalized patients revealed that these events were asso- ciated with 12% mortality and 35% risk of readmission within 3 months after discharge. Acute interventions lacking effective- ness in a substantial proportion of admissions for COPD. New interventions are warranted. Bacterial infections are responsible for approximately half of acute exacerbations of COPD. Guidelines, therefore, recommend antibiotic therapy for patients with more severe symptoms, with treatment typically lasting 5–7 days. Though such intervention has been shown to reduce the risk of subsequent

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PRACTICEUPDATE CONFERENCE SERIES • ERS 2018