Table 2.
Exacerbation Outcomes by Reported History of Exacerbations in the Previous 12 Months (Efficacy Estimand, mITT Population)
| BGF MDI 320/18/9.6 μg | GFF MDI 18/9.6 μg | BFF MDI 320/9.6 μg | BUD/FORM DPI 400/12 μg | |
|---|---|---|---|---|
| Overall population | ||||
| Patients, N | N=639 | N=625 | N=314 | N=318 |
| Rate of moderate/severe COPD exacerbations | ||||
| Number of events, n | 132 | 228 | 74 | 77 |
| Adjusted annualized rate (SE) | 0.46 (0.05) | 0.95 (0.09) | 0.56 (0.08) | 0.55 (0.08) |
| Rate ratio, BGF MDI vs comparator (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 |
| Time to first moderate/severe COPD exacerbation | ||||
| Number of patients with exacerbations, n (%) | 108 (16.9) | 157 (25.1) | 65 (20.7) | 61 (19.2) |
| Hazard ratio, BGF MDI vs comparator (95% CI) | – | 0.59 (0.46, 0.76) | 0.75 (0.55, 1.02) | 0.85 (0.62, 1.17) |
| Cox regression p-value | – | <0.0001 | 0.0635 | 0.3225 |
| Log rank p-value | – | 0.0001 | 0.0281 | 0.0832 |
| Rate of severe COPD exacerbations | ||||
| Number of events, n | 17 | 40 | 9 | 12 |
| Adjusted annualized rate (SE) | 0.047 (0.01) | 0.131 (0.03) | 0.055 (0.02) | 0.068 (0.02) |
| Rate ratio, BGF MDI vs comparator (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 |
| No prior exacerbations | ||||
| Patients, N | N=469 | N=473 | N=235 | N=234 |
| Rate of moderate/severe COPD exacerbations | ||||
| Number of events, n | 85 | 147 | 42 | 47 |
| Adjusted annualized rate (SE) | 0.41 (0.06) | 0.80 (0.09) | 0.42 (0.08) | 0.47 (0.09) |
| Rate ratio, BGF MDI vs comparator (95% CI) | – | 0.52 (0.37, 0.72) | 0.98 (0.63, 1.54) | 0.88 (0.57, 1.36) |
| p-value | – | 0.0001 | 0.9384 | 0.5710 |
| Time to first moderate/severe COPD exacerbation | ||||
| Number of patients with exacerbations, n (%) | 72 (15.4) | 105 (22.2) | 38 (16.2) | 37 (15.8) |
| Hazard ratio, BGF MDI vs comparator (95% CI) | – | 0.64 (0.47, 0.86) | 0.92 (0.62, 1.36) | 0.93 (0.62, 1.38) |
| Cox regression p-value | – | 0.0032 | 0.6643 | 0.7105 |
| Log rank p-value | – | 0.0041 | 0.3829 | 0.4415 |
| Rate of severe COPD exacerbations | ||||
| Number of events, n | 12 | 26 | 6 | 6 |
| Adjusted annualized rate (SE) | 0.046 (0.02) | 0.108 (0.03) | 0.043 (0.02) | 0.046 (0.02) |
| Rate ratio, BGF MDI vs comparator (95% CI) | – | 0.42 (0.19, 0.93) | 1.05 (0.36, 3.11) | 0.99 (0.33, 2.92) |
| p-value | – | 0.0316 | 0.9279 | 0.9817 |
| Prior exacerbations | ||||
| Patients, N | N=170 | N=152 | N=79 | N=84 |
| Rate of moderate/severe COPD exacerbations | ||||
| Number of events, n | 47 | 81 | 32 | 30 |
| Adjusted annualized rate (SE) | 0.63 (0.12) | 1.50 (0.24) | 1.05 (0.25) | 0.84 (0.20) |
| Rate ratio, BGF MDI vs comparator (95% CI) | – | 0.42 (0.26, 0.67) | 0.60 (0.34, 1.08) | 0.75 (0.42, 1.35) |
| p-value | – | 0.0003 | 0.0892 | 0.3423 |
| Time to first moderate/severe COPD exacerbation | ||||
| Number of patients with exacerbations, n (%) | 36 (21.2) | 52 (34.2) | 27 (34.2) | 24 (28.6) |
| Hazard ratio, BGF MDI vs comparator (95% CI) | – | 0.51 (0.33, 0.79) | 0.52 (0.32, 0.86) | 0.71 (0.42, 1.20) |
| Cox regression p-value | – | 0.0022 | 0.0110 | 0.2019 |
| Log rank p-value | – | 0.0031 | 0.0052 | 0.0434 |
| Rate of severe COPD exacerbations | ||||
| Number of events, n | 5 | 14 | 3 | 6 |
| Adjusted annualized rate (SE) | * | * | * | * |
Notes: Treatments are compared adjusting for baseline post-bronchodilator percent predicted FEV1 and baseline eosinophil count as continuous covariates and country and inhaled corticosteroid use at screening (yes/no) as categorical covariates using negative binomial regression. *As the number of events is low, this precludes analysis for this group.
Abbreviations: BFF, budesonide/formoterol fumarate; BGF, budesonide/glycopyrrolate/formoterol fumarate; BUD/FORM DPI, budesonide/formoterol fumarate dry powder inhaler; CI, confidence interval; COPD, chronic obstructive pulmonary disease; GFF, glycopyrrolate/formoterol fumarate; MDI, metered dose inhaler; mITT, modified intent-to-treat; SE, standard error.