Skip to main content

Table 2 Efficacy endpoints (mITT population; efficacy estimand)

From: Efficacy of budesonide/glycopyrronium/formoterol metered dose inhaler in patients with COPD: post-hoc analysis from the KRONOS study excluding patients with airway reversibility and high eosinophil counts

  BGF
320/14.4/10 µg
GFF
14.4/10 µg
BFF
320/10 µg
BUD/FORM
400/12 µg
Change from baseline in morning pre-dose trough FEV1 (mL) over weeks 12–24
 Overall population
  n 592 559 278 288
  LSM (SE) 138 (7.0) 118 (7.1) 61 (9.9) 76 (9.8)
   BGF versus comparators
   LSM difference (95% CI) 20 (1, 39) 77 (53, 100) 62 (38, 85)
   p-value 0.0424  < 0.0001  < 0.0001
 Patients not reversible to albuterol, EOS < 300 cells/mm3
 n 285 277 138 140
 LSM (SE) 97 (9.0) 102 (9.2) 28 (12.8) 46 (12.8)
   BGF versus comparators
   LSM difference (95% CI) –5 (–29, 20) 69 (39, 99) 51 (20, 81)
   p-value 0.7041  < 0.0001 0.0011
Rate of moderate-to-severe exacerbations
 Overall population
  n 639 625 314 318
  Patients with exacerbations, n (%) 108 (16.9) 157 (25.1) 65 (20.7) 61 (19.2)
  Adjusted rate per year 0.46 0.95 0.56 0.55
   BGF versus comparators
   Rate ratio (95% CI) 0.48 (0.37, 0.64) 0.82 (0.58, 1.17) 0.83 (0.59, 1.18)
   p-value  < 0.0001 0.2792 0.3120
 Patients not reversible to albuterol, EOS < 300 cells/mm3
  n 319 315 161 153
  Patients with exacerbations, n (%) 56 (17.6) 80 (25.4) 37 (23.0) 39 (25.5)
  Adjusted rate per year 0.46 0.87 0.56 0.68
   BGF versus comparators
   Rate ratio (95% CI) 0.53 (0.37, 0.76) 0.81 (0.51, 1.29) 0.67 (0.43, 1.04)
   p-value 0.0005 0.3770 0.0756
Rate of severe exacerbations
 Overall population
  n 639 625 314 318
  Patients with exacerbations, n (%) 17 (2.7) 33 (5.3) 9 (2.9) 11 (3.5)
  Adjusted rate per year 0.05 0.13 0.05 0.07
   BGF versus comparators
   Rate ratio (95% CI) 0.36 (0.18, 0.70) 0.85 (0.34, 2.13) 0.69 (0.29, 1.61)
   p-value 0.0026 0.7363 0.3861
 Patients not reversible to albuterol, EOS < 300 cells/mm3
  n 319 315 161 153
  Patients with exacerbations, n (%) 11 (3.4) 20 (6.3) 7 (4.3) 3 (2.0)
  Adjusted rate per year 0.07 0.18 0.10 0.03
   BGF versus comparators
   Rate ratio (95% CI) 0.40 (0.17, 0.94) 0.74 (0.24, 2.30) 2.10 (0.50, 8.81)
   p-value 0.0365 0.6057 0.3096
  1. Overall population moderate/severe data from [4]
  2. Treatments were compared adjusting for baseline post-bronchodilator percent predicted FEV1 and baseline eosinophil count as continuous covariates and baseline COPD exacerbations history (0, 1, ≥ 2), country, and ICS use at screening as categorical covariates using negative binomial regression. Time at risk of experiencing an exacerbation was used as an offset variable in the model
  3. BFF, budesonide/formoterol fumarate dihydrate; BGF, budesonide/glycopyrronium/formoterol fumarate dihydrate; BUD/FORM DPI, budesonide/formoterol fumarate dihydrate dry powder inhaler; CI, confidence interval; EOS, blood eosinophil count; FEV1, forced expiratory volume in 1 s; GFF, glycopyrronium/formoterol fumarate dihydrate; LSM, least squares mean; MDI, metered dose inhaler; mITT, modified intent-to-treat; SE, standard error