Comparison of three combined pharmacological approaches with tiotropium monotherapy in stable moderate to severe COPD: A systematic review

BackgroundGuidelines recommend the use of inhaled long-acting bronchodilators, inhaled corticosteroids (ICS) and their combinations for maintenance treatment of moderate to severe COPD. However, there are limited data supporting combination therapy.MethodsThis systematic review assessed the efficacy of three therapeutic approaches: tiotropium plus long-acting beta2-agonist (LABA) (“dual” therapy), LABA/ICS (“combined” therapy), and tiotropium plus LABA/ICS (“triple” therapy), all compared with tiotropium monotherapy. Randomized controlled trials were identified after a search of different databases of published and unpublished trials.ResultsTwenty trials (6803 participants) were included. “Dual” therapy showed significant improvements in forced volume in the first second (FEV1), health-related quality of life (HRQoL), and dyspnea. However, it failed to reduce the risk of COPD exacerbations. Compared with tiotropium, “combined” therapy presented modest but significant effects on FEV1, HRQoL, and dyspnea. Again, there was no significant difference in exacerbations, but it was associated with a significant increase of serious adverse effects (SAE) (number need to treat for harm [NNTH] = 20; 95% CI: 11–119). Finally, “triple therapy” increased FEV1, improved HRQoL (both benefits exceeded minimal important differences) and decrease COPD exacerbations in anon-significant way. (Odds ratio [OR] = 0.57; 95% CI: 0.24 to 1.37, p = 0.21).Conclusions“Dual” and “triple” therapy seem like the most promising for patients with moderate to very severe COPD. However, data are still scarce and studies too short to generate a strong recommendation. Future studies should examine long-term efficacy and safety.

► Guidelines recommended LABA, ICS and their combinations for moderate-severe COPD. ► Tiotropium/LABA and Tiotropium/LABA/ICS seem like the most promising approaches. ► However, data are scarce to be able to generate strong therapeutic recommendations.