PURPOSE: Addition of a long-acting β2-agonist (LABA) to tiotropium provides significantly increased and maintained bronchodilation over either treatment alone in COPD patients. The LABA formoterol has been formulated for nebulization (formoterol fumarate inhalation solution; FFIS, 20 mcg) and demonstrated comparable efficacy to formoterol dry powder inhaler. A randomized, placebo-controlled, double-blind trial was conducted to evaluate the efficacy and safety of nebulized formoterol in subjects receiving tiotropium as maintenance treatment for COPD.
METHODS: COPD subjects (N = 130; ≥25% to <65% predicted FEV1) received tiotropium 18 mcg once daily during a 7-14 day run-in period, followed by randomization to receive nebulized FFIS (FFIS/TIO) or nebulized placebo (PL/TIO) twice daily, while maintaining once daily tiotropium treatment for 6 weeks. Efficacy was assessed by spirometry.
RESULTS: Baseline characteristics of enrolled subjects (FFIS/TIO: 66; PL/TIO: 63) were comparable between groups, with 61% of subjects aged ≥65 years and a mean pre-bronchodilator FEV1 38% predicted. At Week 6, serial spirometry results showed a standardized absolute FEV1 AUC 0-3 of 1.51 L for FFIS/TIO-treated subjects versus 1.33 L for PL/TIO-treated subjects (p<0.0001), representing a mean improvement of 185 mL (95% CI: 102 - 267). Adverse events (AE) occurred with less frequency in subjects receiving concomitant therapy with FFIS and tiotropium as compared to tiotropium monotherapy and nebulized placebo (22.7% vs 38.7%). A similar finding was observed with incidence of COPD exacerbations (3.0% vs 8.1%) and serious AEs (0 vs 3.2%).
CONCLUSION: In a placebo-controlled trial, concomitant therapy with twice daily nebulized formoterol and once daily tiotropium provided statistically significant and clinically relevant improvements in bronchodilation over tiotropium alone, with no evidence of increased adverse events.
CLINICAL IMPLICATIONS: Nebulized formoterol can be safely used with long-acting anticholinergics to improve bronchodilation in COPD patients.
DISCLOSURE: Donald Tashkin, No Product/Research Disclosure Information; Grant monies (from industry related sources) Dr. Donald Tashkin Disclosure: Dey LP, Boehringer Ingelheim, GlaxoSmithKline, AstraZeneca, Schering Plough, and Medicinova; Employee Dey, LP, Dr. Kimberly Denis-Mize and Mike Rinehart are employees of Dey LP; Consultant fee, speaker bureau, advisory committee, etc. Consultant, Speaker Bureau, and/or Advisory Committee Member: Dey LP, Novartis/Genentech, Schering Plough, AstraZeneca, Boehringer Ingelheim, and Teva Pharmaceuticals