Formoterol and Tiotropium Compared With Tiotropium Alone for Treatment of COPD

Abstract

Combined use of beta(2)-agonists and anticholinergic bronchodilators may have complementary benefits in patients with chronic obstructive pulmonary disease (COPD). The objective of this study was to compare combination treatment with formoterol (FORM) plus tiotropium (TIO) versus treatment with TIO alone in patients with COPD. In this active-controlled, double-blind, multicenter trial, a total of 255 subjects with diagnosed COPD were randomized to 12 weeks of either a combination of FORM 12 microg twice-daily plus TIO 18 microg once-daily in the morning (QD AM) or monotherapy with TIO 18 microg QD AM. The primary efficacy variable was the area under the curve for forced expiratory volume in 1 second measured 0 to 4 hours after AM dosing (FEV(1) AUC(0-4h)). Significantly greater improvements in the FEV(1) AUC(0-4h) were seen with FORM + TIO (n = 116) versus TIO (n = 124) at all time points. The increase in FEV(1) 5 minutes after the first dose was 180 mL with FORM + TIO versus 40 mL with TIO (p < 0.001). At endpoint, FEV(1) AUC(0-4h) increased 340 mL with FORM + TIO versus 170 mL with TIO (p < 0.001). Improvements in trough FEV(1) with FORM + TIO versus TIO were 180 mL and 100 mL, respectively (p < 0.01). Significantly greater reductions from baseline in symptom scores (p < 0.05) and daytime albuterol use (p < 0.04) were seen at endpoint with combination FORM + TIO versus TIO monotherapy. Both treatments were well tolerated. This study demonstrated that concurrent treatment with FORM + TIO results in greater therapeutic benefits than TIO alone.

A Network Meta-Analysis of Long-Acting Muscarinic Antagonist (LAMA) and Long-Acting β2-Agonist (LABA) Combinations in COPD

“…LABA combination therapy compared with TIO monotherapy are consistent with results from several RCTs which directly compared various LAMA ? LABA therapies with TIO [14][15][16][17][18][19][20]. This observation is therefore not unexpected and could be attributed to the direct agonist effect of the added LABA, as well as possible synergistic effects [13].…”

“…In the last decade, multiple randomized controlled trials (RCTs) have reported that improvements in lung function and patient-reported outcomes (PROs) can be achieved with LAMA ? LABA combinations compared with the component monotherapies for patients with stable COPD, with no differences in safety [14][15][16][17][18][19][20].…”

“…Included trials were required to report outcomes within a 4-week window at 12 (8)(9)(10)(11)(12)(13)(14)(15)(16) weeks and/or 24 (20)(21)(22)(23)(24)(25)(26)(27)(28) weeks. Outcomes of interest were: trough forced expiratory volume in 1 s (FEV 1 ), and the subjective PROs of breathlessness assessed by the Transition Dyspnea Index (TDI) focal score, health-related quality of life (HRQoL) assessed by the St George's Respiratory Questionnaire (SGRQ) total score, and rescue short-acting b 2 -agonist medication use (puffs/day).…”

Umeclidinium/Vilanterol Versus Tiotropium/Olodaterol in Maintenance-Naïve Patients with Moderate Symptomatic Chronic Obstructive Pulmonary Disease: A Post Hoc Analysis

“…With a growing body of evidence demonstrating the benefits of dual bronchodilation over monotherapy in a number of clinical settings [4,[9][10][11][12]41], focus is now turning to the relative benefits of different bronchodilator combinations [14]. Indirect evidence from network meta-analyses indicate an efficacy gradient within the LAMA/LABA class with respect to lung function [14,15,23], and this study, the first head-to-head study of UMEC/VI and TIO/ OLO, confirmed the results of the indirect comparisons in both an all-comer and MN population [21].…”

“…A majority of patients who receive LAMA or LABA monotherapy continue to experience ongoing moderate-to-severe dyspnea, regardless of the level of lung function impairment [6], and this symptom persistence can be associated with poor health status, as well as a higher risk for moderate and severe exacerbations and augmented disease management costs [7,8]. There is now a large body of evidence to show that LAMA/LABA combinations consistently improve lung function, breathlessness and health status with no increased incidence of adverse events (AEs), compared with either LABA or LAMA alone [4,[9][10][11][12][13][14][15]. As such, LAMA/LABA combination therapy is recommended as initial therapy in most patients with persistent COPD symptoms [1].…”