Chronic obstructive pulmonary disease (COPD) is characterized by frequent exacerbations.

To evaluate the comparative effectiveness and adverse events (AEs) of pharmacologic interventions for adults with exacerbation of COPD.

English-language searches of several bibliographic sources from database inception to 2 January 2019.

68 randomized controlled trials that enrolled adults with exacerbation of COPD treated in out- or inpatient settings other than intensive care and compared pharmacologic therapies with placebo, “usual care,” or other pharmacologic interventions.

Two reviewers independently extracted data and rated study quality and strength of evidence (SOE).

Compared with placebo or management without antibiotics, antibiotics given for 3 to 14 days were associated with increased exacerbation resolution at the end of the intervention (odds ratio [OR], 2.03 [95% CI, 1.47 to 2.80]; moderate SOE) and less treatment failure at the end of the intervention (OR, 0.54 [CI, 0.34 to 0.86]; moderate SOE), independent of severity of exacerbations in out- and inpatients. Compared with placebo in out- and inpatients, systemic corticosteroids given for 9 to 56 days were associated with less treatment failure at the end of the intervention (OR, 0.01 [CI, 0.00 to 0.13]; low SOE) but also with a higher number of total and endocrine-related AEs. Compared with placebo or usual care in inpatients, other pharmacologic interventions (aminophyllines, magnesium sulfate, anti-inflammatory agents, inhaled corticosteroids, and short-acting bronchodilators) had insufficient evidence, showing either no or inconclusive effects (with the exception of the mucolytic erdosteine) or improvement only in lung function.

Scant evidence for many interventions; several studies had unclear or high risk of bias and inadequate reporting of AEs.

Antibiotics and systemic corticosteroids reduce treatment failure in adults with mild to severe exacerbation of COPD.

Agency for Healthcare Research and Quality. (PROSPERO: CRD42018111609)