Combination inhaled steroid and long-acting beta2 -agonist in addition to tiotropium versus tiotropium or combination alone for chronic obstructive pulmonary disease

Q1Q1Revisión1-60Background The long‐acting bronchodilator tiotropium and single‐inhaler combination therapy of inhaled corticosteroids and long‐acting beta2‐agonists (ICS/LABA) are commonly used for maintenance treatment of patients with chronic obstructive pulmonary disease (COPD). Combining these treatments, which have different mechanisms of action, may be more effective than administering the individual components. Objectives To assess relative effects of the following treatments on markers of exacerbations, symptoms, quality of life and lung function in patients with COPD. • Tiotropium plus LABA/ICS versus tiotropium. • Tiotropium plus LABA/ICS versus LABA/ICS. Search methods We searched the Cochrane Airways Group Specialised Register of Trials (April 2015), ClinicalTrials.gov (www.ClinicalTrials.gov), the World Health Organization (WHO) trials portal and reference lists of relevant articles. Selection criteria We included parallel, randomised controlled trials (RCTs) lasting three months or longer conducted to compare ICS and LABA combination therapy in addition to inhaled tiotropium versus tiotropium alone or combination therapy alone. Data collection and analysis We independently assessed trials for inclusion, then extracted data on trial quality and outcome results. We contacted study authors to ask for additional information. We collected trial information on adverse effects. Main results Tiotropium plus LABA/ICS versus tiotropium We included six studies (1902 participants) with low risk of bias that compared tiotropium in addition to inhaled corticosteroid and long‐acting beta2‐agonist combination therapy versus tiotropium alone. We found no statistically significant differences in mortality between treatments (odds ratio (OR) 1.80, 95% confidence interval (CI) 0.55 to 5.91; two studies; 961 participants) as well as in the all‐cause hospitalisations (OR 0.84, 95% CI 0.53 to 1.33; two studies; 961 participants). The effect on exacerbations was heterogeneous among trials and was not meta‐analysed. Health‐related quality of life measured by St. George’s Respiratory Questionnaire (SGRQ) showed a statistically significant improvement in total scores with use of tiotropium + LABA/ICS compared with tiotropium alone (mean difference (MD) ‐3.46, 95% CI ‐5.05 to ‐1.87; four studies; 1446 participants). Lung function was significantly different in the combined therapy (tiotropium + LABA/ICS) group, although average benefit with this therapy was small. None of the included studies included exercise tolerance as an outcome. A pooled estimate of these studies did not show a statistically significant difference in adverse events (OR 1.16, 95% CI 0.92 to 1.47; four studies; 1363 participants), serious adverse events (OR 0.86, 95% CI 0.57 to 1.30; four studies; 1758 participants) and pneumonia (Peto OR 1.62, 95% CI 0.54 to 4.82; four studies; 1758 participants). Tiotropium plus LABA/ICS versus LABA/ICS One of the six studies (60 participants) also compared combined therapy (tiotropium + LABA/ICS) versus LABA/ICS therapy alone. This study was affected by lack of power; therefore results did not allow us to draw conclusions for this comparison. Authors' conclusions This review update includes three additional studies and provides new low quality evidence supporting the finding that tiotropium + LABA/ICS‐based therapy improves the disease‐specific quality of life. The current evidence is insufficient to support the benefit of tiotropium + LABA/ICS‐based therapy for mortality, hospital admission or exacerbations (moderate and low quality evidence). Compared with use of tiotropium alone, tiotropium + LABA/ICS‐based therapy does not seem to increase undesirable effects nor serious non‐fatal adverse events