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

Background The long-acting bronchodilator tiotropium and single inhaler combination therapy of inhaled corticosteroids and long-acting beta(2)-agonists are both commonly used for maintenance treatment of chronic obstructive pulmonary disease. Combining these treatments, which have different mechanisms of action, may be more effective than the individual components. However, the benefits and risks of using tiotropium and combination therapy together for the treatment of chronic obstructive pulmonary disease are unclear. Objectives To assess the relative effects of inhaled corticosteroid and long-acting beta(2)-agonist combination therapy in addition to tiotropium compared to tiotropium or combination therapy alone in patients with chronic obstructive pulmonary disease. Search strategy We searched the Cochrane Airways Group Specialised Register of trials (July 2010) and reference lists of articles. Selection criteria We included parallel, randomised controlled trials of three months or longer, comparing inhaled corticosteroid and long-acting beta(2)-agonists combination therapy in addition to inhaled tiotropium against tiotropium alone or combination therapy alone. Data collection and analysis We independently assessed trials for inclusion and then extracted data on trial quality and outcome results. We contacted study authors for additional information. We collected information on adverse effects from the trials. Main results Three trials (1021 patients) were included comparing tiotropium in addition to inhaled corticosteroid and long-acting beta2-agonist combination therapy to tiotropium alone. The duration, type of combination treatment and definition of outcomes varied. The limited data led to wide confidence intervals and there was no significant statistical difference in mortality, participants with one or more hospitalisations, episodes of pneumonia or adverse events. The results on exacerbations were heterogeneous and were not combined. The mean health-related quality of life and lung function were significantly different when combination therapy was added to tiotropium, although the size of the average benefits of additional combination therapy were small, St George's Respiratory Questionnaire (MD -2.49; 95% CI -4.04 to -0.94) and forced expiratory volume in one second (MD 0.06 L; 95% CI 0.04 to 0.08). One trial (60 patients) compared tiotropium plus combination therapy to combination therapy alone. The results from the trial were insufficient to draw firm conclusions for this comparison. Authors' conclusions To date there is uncertainty regarding the long-term benefits and risks of treatment with tiotropium in addition to inhaled corticosteroid and long-acting beta(2)-agonist combination therapy on mortality, hospitalisation, exacerbations of COPD and pneumonia. The addition of combination treatment to tiotropium has shown improvements in average health-related quality of life and lung function.