Background
Methods
Study design
Statistical analysis
Results
Incidence of CID
Overall population | GOLD 2 | GOLD 3 | GOLD 4 | |
---|---|---|---|---|
Total UPLIFT population (placebo and tiotropium combined) | ||||
Number of patients, n (%) | 5652 (100.0) | 2603 (100.0) | 2505 (100.0) | 481 (100.0) |
At least one of SGRQ deterioration (decrease of ≥4 units), trough FEV1 decline ≥100 mL or moderate/severe exacerbation | 4741 (83.9) | 2175 (83.6) | 2127 (84.9) | 388 (80.7) |
Moderate/severe exacerbation | 3814 (67.5) | 1615 (62.0) | 1796 (71.7) | 357 (74.2) |
Trough FEV1 decline ≥100 mL | 2503 (44.3) | 1344 (51.6) | 1031 (41.2) | 100 (20.8) |
SGRQ score increase ≥4 units | 2339 (41.4) | 1081 (41.5) | 1054 (42.1) | 178 (37.0) |
Patients with confirmed FEV1decline or SGRQ deterioration at time points after the initial decline (available assessments) | ||||||||
---|---|---|---|---|---|---|---|---|
Months after confirmed FEV1decline or SGRQ increase | ||||||||
6 | 12 | 18 | 24 | 30 | 36 | 42 | 48 | |
FEV1decline | ||||||||
No. of patients with decline, n (%) | 1924/1924 (100) | 1239/1661 (74.6) | 1091/1447 (75.4) | 895/1199 (74.6) | 754/966 (78.1) | 604/755 (80.0) | 419/549 (76.3) | 280/343 (81.6) |
Mean FEV1 change from baseline, mL (SD) | −223 (114) | −193 (176) | −202 (187) | −214 (195) | −237 (212) | −256 (224) | −258 (230) | −280 (224) |
Median FEV1 change from baseline mL (min, max) | −190 (−1090, −40) | −180 (−1240, 850) | −200 (−1000, 0.630) | −210 (−1070, 0.740) | −240 (−1190, 650) | −240 (−1200, 490) | −250 (−980, 460) | −270 (−920, 670) |
SGRQ deterioration | ||||||||
No. of patients with deterioration, n (%) | 1785/1785 (100) | 1140/1510 (75.5) | 941/1301 (72.3) | 776/1067 (72.7) | 629/843 (74.6) | 462/617 (74.9) | 303/388 (78.1) | |
Mean SGRQ change from baseline (SD) | 12.5 (7.5) | 10.6 (10.7) | 10.2 (11.4) | 10.7 (12.3) | 11.3 (12.6) | 11.8 (12.8) | 12.3 (12.8) | |
Median SGRQ score change from baseline (min, max) | 10.5 (4.0, 53.1) | 9.5 (−48.4, 53.9) | 9.3 (−44.2, 67.8) | 10.2 (−44.5, 69.6) | 10.7 (−36.6, 54.6) | 10.9 (−33.8, 50.1) | 11.9 (−29.8, 47.3) |
Relative timing of events
Overall | GOLD 2 | GOLD 3 | GOLD 4 | |
---|---|---|---|---|
Patients with both confirmed FEV1 decline and confirmed SGRQ deterioration, n (%) | 1344 (100.0) | 698 (100.0) | 575 (100.0) | 54 (100.0) |
On same assessment | 240 (17.9) | 121 (17.3) | 108 (18.8) | 9 (16.7) |
FEV1 decline before SGRQ deterioration | 620 (46.1) | 350 (50.1) | 239 (41.6) | 20 (37.0) |
SGRQ deterioration before FEV1 decline | 484 (36.0) | 227 (32.5) | 228 (39.7) | 25 (46.3) |
Moderate/severe exacerbation before FEV1 and SGRQ deterioration | 546 (40.6) | 246 (35.2) | 269 (46.8) | 24 (44.4) |
Patients with confirmed FEV1 decline and no confirmed SGRQ deterioration, n (%) | 1160 (100.0) | 644 (100.0) | 459 (100.0) | 46 (100.0) |
Moderate/severe exacerbation before FEV1 decline | 460 (39.7) | 231 (35.9) | 199 (43.4) | 24 (52.2) |
Unconfirmed SGRQ deterioration | 302 (26.0) | 180 (28.0) | 109 (23.7) | 10 (21.7) |
On same assessment as confirmed FEV1 decline | 34 (2.9) | 20 (3.1) | 12 (2.6) | 1 (2.2) |
Before confirmed FEV1 decline | 116 (10.0) | 72 (11.2) | 36 (7.8) | 7 (15.2) |
Patients with confirmed SGRQ and no confirmed FEV1 deterioration, n (%) | 995 (100.0) | 383 (100.0) | 479 (100.0) | 124 (100.0) |
Moderate/severe exacerbation before SGRQ deterioration | 574 (57.7) | 184 (48.0) | 305 (63.7) | 80 (64.5) |
Unconfirmed FEV1 deterioration | 284 (28.5) | 141 (36.8) | 126 (26.3) | 15 (12.1) |
On same assessment as confirmed SGRQ deterioration | 50 (5.0) | 23 (6.0) | 24 (5.0) | 3 (2.4) |
Before confirmed SGRQ deterioration | 151 (15.2) | 80 (20.9) | 64 (13.4) | 5 (4.0) |
Response to treatment
Event, n (%) | Time to first event treatment comparison (tiotropium–placebo) | |||
---|---|---|---|---|
Tiotropium 18 μg | Placebo | HR (95% CI) | Pvalue | |
Overall | 2811 (100.0) | 2841 (100.0) | ||
SGRQ deterioration, trough FEV1 decline ≥100 mL, moderate/severe exacerbation | 2310 (82.2) | 2431 (85.6) | 0.71 (0.67, 0.75) | < 0.0001 |
Moderate/severe exacerbation | 1884 (67.0) | 1930 (67.9) | 0.86 (0.81, 0.92) | < 0.0001 |
Trough FEV1 decline ≥100 mL | 1028 (36.6) | 1475 (51.9) | 0.53 (0.49, 0.58) | < 0.0001 |
SGRQ score increase ≥4 units | 1077 (38.3) | 1262 (44.4) | 0.72 (0.66, 0.78) | < 0.0001 |
GOLD 2 | 1310 (100.0) | 1293 (100.0) | ||
SGRQ deterioration, trough FEV1 decline ≥100 mL, moderate/severe exacerbation | 1053 (80.4) | 1122 (86.8) | 0.70 (0.65, 0.77) | < 0.0001 |
Moderate/severe exacerbation | 780 (59.5) | 835 (64.6) | 0.83 (0.75, 0.92) | 0.0002 |
Trough FEV1 decline ≥100 mL | 564 (43.1) | 780 (60.3) | 0.54 (0.49, 0.61) | < 0.0001 |
SGRQ score increase ≥4 units | 487 (37.2) | 594 (45.9) | 0.71 (0.63, 0.80) | < 0.0001 |
GOLD 3 | 1239 (100.0) | 1266 (100.0) | ||
SGRQ deterioration, trough FEV1 decline ≥100 mL, moderate/severe exacerbation | 1036 (83.6) | 1091 (86.2) | 0.69 (0.63, 0.75) | < 0.0001 |
Moderate/severe exacerbation | 896 (72.3) | 900 (71.1) | 0.86 (0.78, 0.94) | 0.0010 |
Trough FEV1 decline ≥100 mL | 413 (33.3) | 618 (48.8) | 0.51 (0.45, 0.58) | < 0.0001 |
SGRQ score increase ≥4 units | 491 (39.6) | 563 (44.5) | 0.71 (0.63, 0.81) | < 0.0001 |
GOLD 4 | 231 (100.0) | 250 (100.0) | ||
SGRQ deterioration, trough FEV1 decline ≥100 mL, moderate/severe exacerbation | 197 (85.3) | 191 (76.4) | 0.90 (0.74, 1.10) | 0.3079 |
Moderate/severe exacerbation | 186 (80.5) | 171 (68.4) | 1.00 (0.81, 1.23) | 0.9798 |
Trough FEV1 decline ≥100 mL | 41 (17.7) | 59 (23.6) | 0.57 (0.39, 0.86) | 0.0066 |
SGRQ score increase ≥4 units | 90 (39.0) | 88 (35.2) | 0.83 (0.62, 1.11) | 0.2105 |
Risk of future exacerbations and death
Outcome at Month 6 | Patients with any CID event vs. patients without, HR (95% CI) | Patients with confirmed FEV1 decline vs. patients without, HR (95% CI) | Patients with confirmed SGRQ deterioration vs. patients without, HR (95% CI) | Patients with moderate/severe exacerbation vs. patients without, HR (95% CI) |
---|---|---|---|---|
Overall population | ||||
Moderate/severe exacerbation | 1.79 (1.67, 1.92) | 1.11 (1.02, 1.22) | 1.30 (1.18, 1.43) | 2.36 (2.20, 2.53) |
Severe exacerbation | 1.67 (1.49, 1.86) | 1.06 (0.92, 1.23) | 1.66 (1.44, 1.91) | 1.88 (1.68, 2.11) |
Death up to Day 1470 | 1.21 (1.06, 1.39) | 1.09 (0.92, 1.31) | 1.27 (1.05, 1.54) | 1.22 (1.05, 1.41) |
GOLD 2 | ||||
Moderate/severe exacerbation | 1.73 (1.56, 1.92) | 1.15 (1.01, 1.30) | 1.24 (1.07, 1.44) | 2.49 (2.23, 2.78) |
Severe exacerbation | 1.58 (1.30, 1.92) | 1.23 (0.97, 1.55) | 1.77 (1.37, 2.27) | 1.79 (1.46, 2.21) |
Death up to Day 1470 | 1.21 (0.95, 1.55) | 1.26 (0.94, 1.68) | 1.36 (0.98, 1.90) | 1.01 (0.75, 1.35) |
GOLD 3 | ||||
Moderate/severe exacerbation | 1.84 (1.67, 2.04) | 1.18 (1.03, 1.35) | 1.32 (1.15, 1.52) | 2.21 (1.99, 2.45) |
Severe exacerbation | 1.69 (1.45, 1.96) | 1.08 (0.88, 1.33) | 1.57 (1.29, 1.92) | 1.79 (1.54, 2.09) |
Death up to Day 1470 | 1.20 (0.99, 1.45) | 1.17 (0.91, 1.51) | 1.30 (1.00, 1.70) | 1.15 (0.94, 1.41) |
GOLD 4 | ||||
Moderate/severe exacerbation | 1.84 (1.47, 2.32) | 1.35 (0.85, 2.15) | 1.57 (1.14, 2.16) | 1.97 (1.55, 2.50) |
Severe exacerbation | 1.69 (1.26, 2.25) | 2.38 (1.46, 3.88) | 1.81 (1.23, 2.67) | 1.46 (1.09, 1.97) |
Death up to Day 1470 | 1.16 (0.84, 1.60) | 1.52 (0.88, 2.63) | 1.00 (0.60, 1.66) | 1.22 (0.87, 1.70) |