Skip to main content

Advertisement

Table 3 LABA and LAMA combinations: current evidence

From: Combination bronchodilator therapy in the management of chronic obstructive pulmonary disease

Combination (manufacturer) Reference Reported results
Free combinations
GSK233705: 20 or 50 μg BID; salmeterol: 50 μg BID Beier et al. [61] Larger mean increases from baseline trough FEV1 vs placebo with 20 μg GSK233705 + salmeterol (203 mL) and 50 μg GSK233705 + salmeterol (215 mL) vs monotherapy with tiotropium (101 mL) or salmeterol (118 mL)
Tiotropium: 18 μg QD; arformoterol: 15 μg BID Tashkin et al. [60] Greater improvement in FEV1 AUC0-24 from baseline with combination (0.22 L) vs monotherapy with either arformoterol (0.10 L) or tiotropium (0.08 L); p < 0.001
Greater improvement in TDI with combination (3.1) vs monotherapy with either arformoterol (2.3; CI 0.03, 1.70) or tiotropium (1.8; CI 0.50, 2.20)
Tiotropium: 18 μg QD; formoterol: 20 μg BID Hanania et al. [65] FEV1 AUC0-3 greater with combination (1.57 L) vs tiotropium alone (1.38 L); p < 0.0001
Reduced use of rescue medication vs tiotropium alone; p < 0.05
Tiotropium: 18 μg QD; formoterol: 20 μg BID Tashkin et al. [56] Greater FEV1 AUC0-3 with combination (1.52 L) vs tiotropium alone (1.34 L); p < 0.0001
Greater improvement in TDI with combination than tiotropium alone (2.30 vs 0.16; mean difference of 1.80); 95% CI 0.86, 2.74, p < 0.0002
Tiotropium: 18 μg QD; formoterol: 12 μg BID Tashkin et al. [55] Greater improvement in FEV1 AUC0-4 from baseline with combination (0.34 L) vs tiotropium alone (0.17 L); p < 0.001
Dyspnea significantly improved with combination at week 8 (1.86) vs tiotropium alone (1.01); p = 0.013
Reduced use of rescue medication vs tiotropium alone; p < 0.04
Tiotropium: 18 μg QD; formoterol: 12 μg QD or BID Terzano et al. [66] Greater improvement in FEV1 with combination vs tiotropium alone at day 30 (0.16 L); p = 0.0001
Improvement in dyspnea with combinations (2.32-2.61) vs tiotropium alone (1.0); p < 0.05
Lower rescue medication use with combinations (0.71-0.80 puffs/day) vs tiotropium alone (2.14 puffs/day); p < 0.05
Tiotropium: 18 μg QD; formoterol: 12 μg QD or BID van Noord et al. [47] Greater average improvement in FEV1 AUC0-24 0.16-0.20 L with combinations vs 0.08 L with tiotropium alone; p < 0.05
Lower rescue medication use with combinations vs tiotropium alone; p < 0.01 (daily rescue medication use with tiotropium + formoterol QD or BID) and p < 0.05 (tiotropium + formoterol BID)
Tiotropium: 18 μg QD; formoterol: 12 μg QD or BID van Noord et al. [49] Average improvement in daytime (0.234 L) and night-time FEV1 (0.086 L) with combination vs monotherapy with tiotropium (p ≤ 0.001) or formoterol (p ≤ 0.01)
Lower rescue medication use with combination (1.81 puffs/day) vs monotherapies (2.37-2.41 puffs/day); p < 0.01
Tiotropium: 18 μg QD; formoterol: 10 μg BID Vogelmeier et al. [54] Improvement in FEV1 2 h post-dose after 24 weeks with combination vs formoterol alone (p = 0.044)
Tiotropium: 18 μg QD; indacaterol: 150 μg QD Mahler et al. [50] Greater increase in trough FEV1 from baseline with combination: 70–80 mL difference vs tiotropium alone (p < 0.001)
Improved trough IC with combination vs tiotropium alone: 100–130 mL; p < 0.01
Less use of albuterol as rescue medication with combination: reduction of 0.8–1.3 puffs/day from baseline vs tiotropium alone
Tiotropium: 18 μg QD; salmeterol: 50 μg BID Aaron et al. [48] No statistical improvement in lung function or hospitalization rates with combination compared to tiotropium monotherapy
Tiotropium: 18 μg QD; salmeterol: 50 μg BID van Noord et al. [59] Improved average FEV1 (0–24 h) with combination (0.142 L) vs monotherapy with either tiotropium (0.07 L) or salmeterol (0.045 L); p < 0.0001
Combination associated with clinically relevant improvements in TDI focal score (p < 0.001)
Fixed-dose combinations
Glycopyrrolate: 36 and 72 μg BID; formoterol: 9.6 μg BID (Pearl Therapeutics) Reisner et al. [53] Increase in FEV1 AUC0–12 on day 7 with combination compared to monotherapy with either of the components, tiotropium, and placebo (p < 0.0001)
Glycopyrrolate: 36 and 72 μg BID; formoterol: 9.6 μg BID (Pearl Therapeutics) Reisner et al. [52] Higher morning pre-trough and peak IC with combination vs placebo (p < 0.0005 and p < 0.005, respectively) or tiotropium monotherapy (p < 0.05 for all comparisons)
Glycopyrrolate: 36 and 72 μg BID; formoterol: 9.6 μg BID (Pearl Therapeutics) Reisner et al. [62] Similar metabolic and cardiac safety profile to tiotropium
Glycopyrronium: 50 μg QD; indacaterol: 300 μg QD (Novartis) van Noord et al. [58] Improved trough FEV1 with combination: 0.226 L difference in trough FEV1 vs placebo (p < 0.001)
Greater peak FEV1 with combination (1.709 L) vs 300 μg indacaterol (1.579 L) and 600 μg indacaterol (1.573 L); p < 0.0001 for both comparisons
Glycopyrronium: 100 μg QD; indacaterol: 600 μg QD (Novartis) Van de Maele et al. [57] Increased trough FEV1 with combination (1.61 L) vs indacaterol monotherapy 300 μg (1.46 L); p < 0.05
Glycopyrronium: 50 μg QD; indacaterol: 110 μg QD (Novartis) Bateman et al. [68] Improved trough FEV1 with combination vs placebo (0.20 L mean difference), indacaterol (0.07 L), glycopyrronium (0.09 L), and tiotropium (0.08 L) monotherapy; p < 0.001
Improved TDI score with combination vs placebo (mean difference 1.09); p < 0.001 and tiotropium (0.51 mean difference); p < 0.05
Improved SGRQ score with combination vs tiotropium (-2.13 mean difference); p < 0.05
Reduced use of rescue medication with combination vs monotherapies (-0.30 to -0.54 mean difference); p < 0.05
Glycopyrronium: 50 μg QD; indacaterol: 110 μg QD (Novartis) Vogelmeier et al. [69] Improvement in trough FEV1 with combination vs salmeterol/fluticasone (mean difference 0.103 L); p < 0.0001
Improvements in TDI score with combination vs salmeterol/fluticasone (mean difference 0.76); p = 0.003
Lower use of rescue medication with combination vs salmeterol/fluticasone (-0.39 puffs/day); p = 0.019)
Glycopyrronium: 50 μg QD; indacaterol: 110 μg QD (Novartis) Dahl et al. [67] Combination increased FEV1 and FVC vs placebo over a 52-week period; p < 0.001
Tiotropium: 5 μg QD; olodaterol: 2, 5, and 10 μg QD (Boehringer Ingelheim) Maltais et al. [51] Higher peak FEV1 for all doses of combination investigated vs tiotropium alone (p ≤ 0.05); higher trough FEV1 response with tiotropium + olodaterol 5/10 μg vs tiotropium alone (p = 0.034)
Tiotropium: 1.25, 2.5, and 5 μg QD; olodaterol: 5 and 10 μg QD (Boehringer Ingelheim) Aalbers et al. [64] Significant improvements in FEV1 for all doses of combination vs olodaterol alone, with evidence of a dose-dependent response
Umeclidinium (GSK573719): 500 μg QD; vilanterol: 25 μg QD (GSK) Feldman et al. [63] Adverse-event rate of 26%, with no single adverse event reported in >1 patient
Combination similar to placebo in terms of cardiac parameters
   Greater change from baseline in trough FEV1 and FEV1 from 0–6 h post-dose with combination vs placebo
  1. PubMed and relevant respiratory congresses were searched for abstracts relating to LAMA/LABA combination therapies.
  2. BID = twice a day; FEV1 = forced expiratory volume in 1 second; QD = once a day; AUC = area under the curve; TDI = Transition Dyspnea Index; CI = confidence interval; IC = inspiratory capacity; SGRQ = St George’s Respiratory Questionnaire.