Optimizing the Development Strategy of Combination Therapy in Respiratory Medicine: From Isolated Airways to Patients
Abstract
The current recommendations for the treatment of chronic obstructive pulmonary disease (COPD) are pushing towards triple combination therapy based on the combination of an inhaled corticosteroid (ICS) associated with two bronchodilator agents. However, dual bronchodilation remains the cornerstone for the treatment of most COPD patients. Combining a long-acting β2 adrenoceptor agonist (LABA) with a long-acting muscarinic antagonist (LAMA) induces appreciable synergistic bronchorelaxant effect in human airways, especially when the medications are combined at isoeffective concentrations. Thus, each LABA/LAMA combination is characterized by a specific range of concentration-ratio at which the drug mixture may induce sustained synergistic interaction. Results of a recent randomized controlled trial (RCT, NCT00696020) and evidences from pre-clinical studies in human isolated airways poses the question whether combining tiotropium 5 μg with olodaterol 5 μg is the best combination option: tiotropium/olodaterol 5/5 μg has the same efficacy profile of tiotropium/olodaterol 5/2 μg, and it is less effective than tiotropium/olodaterol 5/10 μg. Furthermore, tiotropium/olodaterol 5/2 μg, 5/5 μg, and 5/10 μg combinations are generally characterized by the same safety profile. Indeed tiotropium/olodaterol 5/5 μg is effective and safe in COPD, but a different development strategy based on solid data obtained from human isolated airways would have driven towards a better-balanced FDC to be…
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Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design.
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