Background
Methods
Study population
Instruments used in the psychometric analyses
Itch NRS, Skin Pain NRS, ADSS
Other scales
Statistical analyses
Test–retest reliability
Construct validity (convergent and divergent validity)
Known-groups validity (discriminant validity)
Responsiveness
Meaningful change estimation
Anchor-based assessment
Distribution-based methods
Handling of missing data
Results
Characteristics | BREEZE-AD1 (N = 624) | BREEZE-AD2 (N = 615) | BREEZE-AD5 (N = 440) |
---|---|---|---|
Age, years | 35.6 (12.81) | 34.7 (12.77) | 39.5 (16.06) |
Sex, n (%) | |||
Male | 391 (62.7) | 381 (62.0) | 224 (50.9) |
Female | 233 (37.3) | 234 (38.0) | 216 (49.1) |
Race, n (%) | |||
White | 366 (58.9) | 421 (68.5) | 251 (57.3) |
African American | 2 (0.3) | 0 (0) | 80 (18.3) |
Asian | 189 (30.4) | 183 (29.8) | 81 (18.5) |
Other | 64 (10.3) | 11 (1.8) | 26 (5.9) |
Alcohol use, n (%) | |||
Never | 214 (34.3) | 220 (35.8) | 103 (23.4) |
Current | 381 (61.1) | 353 (57.4) | 291 (66.1) |
Former | 29 (4.6) | 42 (6.8) | 46 (10.5) |
Tobacco use, n (%) | |||
Never | 394 (63.1) | 389 (63.3) | 276 (62.7) |
Current | 158 (25.3) | 155 (25.2) | 80 (18.2) |
Former | 72 (11.5) | 71 (11.5) | 84 (19.1) |
Duration since AD diagnosis, years | 25.7 (15.10) | 24.2 (13.86) | 23.6 (16.65) |
Age at time of AD diagnosis, years | 10.2 (14.54) | 10.8 (14.22) | 15.9 (20.30) |
IGA of 3, n (%) | 363 (58.2) | 305 (49.7) | 256 (58.2) |
IGA of 4, n (%) | 261 (41.8) | 309 (50.3) | 184 (41.8) |
EASI | 30.9 (12.45) | 33.5 (13.44) | 27.1 (11.29) |
BSA | 51.0 (22.34) | 53.5 (22.62) | 40.9 (22.73) |
Itch NRS | 6.5 (2.09) | 6.6 (2.17) | 7.2 (2.17) |
Skin Pain NRS | 5.8 (2.47) | 6.05 (2.55) | 6.56 (2.63) |
ADSS Item 2 | 3.0 (4.67) | 1.8 (2.31) | 2.3 (2.89) |
DLQI | 13.6 (7.27) | 14.4 (8.09) | 14.7 (7.28) |
PGI-S-AD | 3.9 (0.82) | 3.9 (0.85) | 4.0 (0.85) |
POEM | 20.7 (5.59) | 20.4 (6.26) | 21.3
(5.62) |
Test–retest reliability
Measure | Study | Baseline to Week 1 | Week 4 to Week 8 | ||
---|---|---|---|---|---|
N | ICCa (95% CI) | N | ICCa (95% CI) | ||
Itch NRS | BREEZE-AD1 | 620 | 0.863 (0.842, 0.882) | 599 | 0.783 (0.750, 0.812) |
BREEZE-AD2 | 608 | 0.853 (0.830, 0.873) | 587 | 0.816 (0.787, 0.841) | |
BREEZE-AD5 | 432 | 0.875 (0.851, 0.896) | 405 | 0.770 (0.727, 0.807) | |
Skin pain NRS | BREEZE-AD1 | 620 | 0.832 (0.806, 0.855) | 599 | 0.773 (0.739, 0.804) |
BREEZE-AD2 | 608 | 0.845 (0.821, 0.866) | 587 | 0.808 (0.778, 0.834) | |
BREEZE-AD5 | 432 | 0.832 (0.801, 0.859) | 405 | 0.753 (0.708, 0.792) | |
ADSS item 1 | BREEZE-AD1 | 620 | 0.839 (0.814, 0.861) | 599 | 0.754 (0.717, 0.786) |
BREEZE-AD2 | 607 | 0.843 (0.819, 0.865) | 587 | 0.776 (0.742, 0.806) | |
BREEZE-AD5 | 432 | 0.834 (0.803, 0.861) | 405 | 0.792 (0.753, 0.826) | |
ADSS item 2 | BREEZE-AD1 | 620 | 0.921 (0.908, 0.932) | 599 | 0.903 (0.887, 0.917) |
BREEZE-AD2 | 607 | 0.765 (0.730, 0.796) | 587 | 0.585 (0.529, 0.635) | |
BREEZE-AD5 | 432 | 0.921 (0.906, 0.934) | 405 | 0.918 (0.901, 0.932) | |
ADSS item 3 | BREEZE-AD1 | 512 | 0.780 (0.743, 0.811) | 353 | 0.703 (0.646, 0.752) |
BREEZE-AD2 | 497 | 0.761 (0.722, 0.796) | 315 | 0.682 (0.618, 0.737) | |
BREEZE-AD5 | 369 | 0.784 (0.741, 0.820) | 239 | 0.671 (0.596, 0.735) |
Construct validity (convergent and divergent validity)
Measure | Correlation | BREEZE-AD1a correlation | BREEZE-AD2a correlation | BREEZE-AD5a correlation | |||
---|---|---|---|---|---|---|---|
Baseline | Week 16 | Baseline | Week 16 | Baseline | Week 16 | ||
Itch NRS | ClinRO | ||||||
EASI | 0.229 | 0.398 | 0.223 | 0.505 | 0.225 | 0.498 | |
PRO | |||||||
PGI-S-AD | 0.762 | 0.767 | 0.759 | 0.788 | 0.752 | 0.834 | |
DLQI | 0.495 | 0.590 | 0.506 | 0.586 | 0.544 | 0.666 | |
POEM | 0.483 | 0.607 | 0.586 | 0.640 | 0.505 | 0.667 | |
Skin pain NRS | ClinRO | ||||||
EASI | 0.222 | 0.338 | 0.225 | 0.455 | 0.251 | 0.444 | |
PRO | |||||||
PGI-S-AD | 0.707 | 0.691 | 0.727 | 0.710 | 0.689 | 0.768 | |
DLQI | 0.529 | 0.549 | 0.591 | 0.582 | 0.586 | 0.658 | |
POEM | 0.474 | 0.575 | 0.634 | 0.621 | 0.536 | 0.657 | |
ADSS item 1 | ClinRO | ||||||
EASI | 0.281 | 0.363 | 0.140 | 0.403 | 0.233 | 0.376 | |
PRO | |||||||
PGI-S-AD | 0.651 | 0.582 | 0.624 | 0.597 | 0.627 | 0.670 | |
DLQI | 0.570 | 0.576 | 0.598 | 0.554 | 0.522 | 0.608 | |
POEM | 0.507 | 0.508 | 0.531 | 0.518 | 0.499 | 0.582 | |
ADSS item 2 | ClinRO | ||||||
EASI | 0.245 | 0.254 | 0.131 | 0.357 | 0.223 | 0.350 | |
PRO | |||||||
PGI-S-AD | 0.451 | 0.424 | 0.435 | 0.446 | 0.449 | 0.495 | |
DLQI | 0.445 | 0.486 | 0.447 | 0.486 | 0.411 | 0.516 | |
POEM | 0.368 | 0.436 | 0.468 | 0.489 | 0.422 | 0.473 | |
ADSS item 3 | ClinRO | ||||||
EASI | 0.298 | 0.237 | 0.152 | 0.394 | 0.187 | 0.300 | |
PRO | |||||||
PGI-S-AD | 0.555 | 0.636 | 0.603 | 0.641 | 0.639 | 0.809 | |
DLQI | 0.516 | 0.466 | 0.526 | 0.505 | 0.516 | 0.581 | |
POEM | 0.439 | 0.472 | 0.460 | 0.474 | 0.403 | 0.563 |
Known-groups validity
Measure | PGI-S-AD category | POEM category | ||||
---|---|---|---|---|---|---|
≤ 3 (no to mild symptoms) | > 3 (moderate to severe symptoms) | 0–7 (clear to mild) | 8–16 (moderate to severe) | 17–28 (severe to very severe) | ||
Itch NRS | BREEZE-AD1 | |||||
Sample size | 118 | 497 | 13 | 125 | 470 | |
LSM (SE) at baseline | 4.22 (0.296) | 7.43 (0.254) | N/Ab | 5.35 (0.322) | 7.46 (0.283) | |
Between-group comparisonsa | – | < 0.0001 | – | N/Ab | < 0.0001 | |
BREEZE-AD2 | ||||||
Sample size | 110 | 490 | 26 | 126 | 445 | |
LSM (SE) at baseline | 3.58 (0.502) | 6.79 (0.471) | 3.05 (0.628) | 5.09 (0.537) | 6.89 (0.510) | |
Between-group comparisonsa | – | < 0.0001 | – | < 0.0001 | < 0.0001 | |
BREEZE-AD5 | ||||||
Sample size | 61 | 364 | 9 | 72 | 342 | |
LSM (SE) at baseline | 3.95 (0.328) | 7.59 (0.260) | N/Ab | 4.89 (0.362) | 7.29 (0.286) | |
Between-group comparisonsa | – | < 0.0001 | – | N/Ab | < 0.0001 | |
Skin pain NRS | BREEZE-AD1 | |||||
Sample Size | 118 | 497 | 13 | 125 | 470 | |
LSM (SE) at baseline | 3.36 (0.372) | 6.73 (0.319) | N/Ab | 4.58 (0.394) | 6.75 (0.346) | |
Between-group comparisonsa | – | < 0.0001 | – | N/Ab | < 0.0001 | |
BREEZE-AD2 | ||||||
Sample size | 110 | 490 | 26 | 126 | 445 | |
LSM (SE) at baseline | 2.94 (0.617) | 6.29 (0.580) | 1.96 (0.723) | 4.09 (0.619) | 6.47 (0.587) | |
Between-group comparisonsa | – | < 0.0001 | – | < 0.0001 | < 0.0001 | |
BREEZE-AD5 | ||||||
Sample size | 61 | 364 | 9 | 72 | 342 | |
LSM (SE) at baseline | 3.55 (0.436) | 7.07 (0.345) | N/Ab | 4.05 (0.446) | 6.83 (0.353) | |
Between-group comparisonsa | – | < 0.0001 | – | N/Ab | < 0.0001 | |
ADSS item 1 | BREEZE-AD1 | |||||
Sample size | 118 | 497 | 13 | 125 | 470 | |
LSM (SE) at baseline | 1.04 (0.167) | 2.36 (0.143) | N/Ab | 1.45 (0.174) | 2.38 (0.152) | |
Between-group comparisonsa | – | < 0.0001 | – | N/Ab | < 0.0001 | |
BREEZE-AD2 | ||||||
Sample size | 110 | 490 | 26 | 126 | 445 | |
LSM (SE) at baseline | 1.06 (0.286) | 2.29 (0.269) | 0.94 (0.341) | 1.53 (0.292) | 2.34 (0.277) | |
Between-group comparisonsa | – | < 0.0001 | – | 0.0089 | < 0.0001 | |
BREEZE-AD5 | ||||||
Sample size | 61 | 364 | 9 | 72 | 342 | |
LSM (SE) at baseline | 1.04 (0.201) | 2.54 (0.159) | N/Ab | 1.38 (0.209) | 2.43 (0.165) | |
Between-group comparisonsa | – | < 0.0001 | – | N/Ab | < 0.0001 | |
ADSS item 2 | BREEZE-AD1 | |||||
Sample size | 118 | 497 | 13 | 125 | 470 | |
LSM (SE) at baseline | 1.18 (0.809) | 3.22 (0.694) | N/A^b | 1.36 (0.805) | 3.35 (0.706) | |
Between-group comparisonsa | – | < 0.0001 | – | N/Ab | 0.0001 | |
BREEZE-AD2 | ||||||
Sample size | 110 | 490 | 26 | 126 | 445 | |
LSM (SE) at baseline | 1.00 (0.622) | 2.11 (0.585) | 0.91 (0.727) | 1.46 (0.622) | 2.15 (0.590) | |
Between-group comparisonsa | – | < 0.0001 | – | 0.2514 | 0.0024 | |
BREEZE-AD5 | ||||||
Sample Size | 61 | 364 | 9 | 72 | 342 | |
LSM (SE) at baseline | 1.12 (0.525) | 2.87 (0.416) | N/Ab | 1.32 (0.529) | 2.79 (0.418) | |
Between-group comparisonsa | – | < 0.0001 | – | N/Ab | 0.0001 | |
ADSS item 3 | BREEZE-AD1 | |||||
Sample Size | 63 | 442 | 10 | 74 | 415 | |
LSM (SE) at baseline | 1.42 (0.175) | 2.46 (0.136) | N/Ab | 1.74 (0.172) | 2.50 (0.139 | |
Between-group comparisonsa | – | < 0.0001 | – | N/Ab | < 0.0001 | |
BREEZE-AD2 | ||||||
Sample size | 60 | 423 | 11 | 84 | 385 | |
LSM (SE) at baseline | 1.30 (0.267) | 2.35 (0.240) | N/Ab | 1.63 (0.266) | 2.38 (0.247) | |
Between-group comparisonsa | – | < 0.0001 | – | N/Ab | < 0.0001 | |
BREEZE-AD5 | ||||||
Sample size | 38 | 324 | 4 | 48 | 309 | |
LSM (SE) at baseline | 1.53 (0.190) | 2.82 (0.137) | N/Ab | 2.02 (0.195) | 2.72 (0.143) | |
Between-group comparisonsa | – | < 0.0001 | - | N/Ab | < 0.0001 |
Responsiveness
POEM groups at week 16 | ||||
---|---|---|---|---|
Much improved (> 1 category improvement) | Improved (1 category improvement) | Stable (No category change) | Declined (≥ 1 category worsening) | |
Itch NRS | ||||
BREEZE-AD1 | ||||
Sample Size | 71 | 198 | 263 | 25 |
Mean (SD) change | − 4.64 (2.333) | − 3.03 (2.025) | − 1.42 (1.986) | 0.10 (1.964) |
Median change | − 4.86 | − 3.14 | − 1.14 | − 0.12 |
Between-group comparisonsa | – | < 0.0001 | < 0.0001 | 0.0007 |
BREEZE-AD2 | ||||
Sample size | 85 | 163 | 263 | 23 |
Mean (SD) at baseline | − 4.49 (2.162) | − 3.01 (2.183) | − 1.47 (2.166) | 0.13 (2.602) |
Median change | − 4.5 | − 2.86 | − 1.29 | 0.07 |
Between-group comparisonsa | – | < 0.0001 | < 0.0001 | 0.0042 |
BREEZE-AD5 | ||||
Sample size | 49 | 104 | 176 | 8 |
Mean (SD) at baseline | − 5.39 (2.523) | − 3.59 (2.245) | − 1.46 (2.109) | − 0.01 (3.105) |
Median change | − 5.43 | − 3.54 | − 1.31 | − 0.21 |
Between-group comparisonsa | – | < 0.0001 | < 0.0001 | 0.1167 |
Skin pain NRS | ||||
BREEZE-AD1 | ||||
Sample size | 71 | 198 | 263 | 25 |
Mean (SD) change | − 4.49 (2.580) | − 2.82 (2.289) | − 1.34 (2.220) | 0.53 (2.236) |
Median change | − 4.52 | − 2.79 | − 1.00 | 0.00 |
Between-group comparisonsa | – | < 0.0001 | < 0.0001 | 0.0002 |
BREEZE-AD2 | ||||
Sample size | 85 | 163 | 263 | 23 |
Mean (SD) at baseline | − 4.60 (2.396) | − 3.17
(2.309) | − 1.36 (2.395) | 0.04 (2.594) |
Median change | − 4.29 | − 2.74 | − 1.29 | 0.25 |
Between-group comparisonsa | – | < 0.0001 | < 0.0001 | 0.0203 |
BREEZE-AD5 | ||||
Sample size | 49 | 104 | 176 | 8 |
Mean (SD) at baseline | − 4.80 (2.842) | − 3.60 (2.398) | − 1.48 (2.354) | 0.21 (4.211) |
Median change | − 4.86 | − 3.57 | − 1.21 | − 0.38 |
Between-group comparisonsa | – | 0.0216 | < 0.0001 | 0.0932 |
ADSS item 1 | ||||
BREEZE-AD1 | ||||
Sample size | 71 | 198 | 263 | 25 |
Mean (SD) change | − 1.40 (1.045) | − 0.98 (0.904) | − 0.51 (0.977) | 0.34 (1.011) |
Median change | − 1.17 | − 0.91 | − 0.29 | 0.00 |
Between-group comparisonsa | – | 0.0022 | < 0.0001 | < 0.0001 |
BREEZE-AD2 | ||||
Sample size | 85 | 163 | 263 | 23 |
Mean (SD) at baseline | − 1.45 (0.924) | − 1.12 (0.951) | − 0.38 (0.937) | 0.10 (0.739) |
Median change | − 1.43 | − 1.00 | − 0.29 | 0.00 |
Between-group comparisonsa | – | 0.0144 | < 0.0001 | 0.0453 |
BREEZE-AD5 | ||||
Sample size | 49 | 104 | 176 | 8 |
Mean (SD) at baseline | − 1.69 (1.245) | − 1.30 (0.956) | − 0.34 (0.842) | − 0.06 (0.973) |
Median change | − 1.71 | − 1.07 | − 0.14 | 0.00 |
Between-group comparisonsa | – | 0.0386 | < 0.0001 | 0.5370 |
ADSS item 2 | ||||
BREEZE-AD1 | ||||
Sample size | 71 | 198 | 263 | 25 |
Mean (SD) change | − 2.47 (4.141) | − 1.60 (2.491) | − 1.05 (2.954) | − 0.04 (1.483) |
Median change | − 1.14 | − 1.00 | − 0.57 | 0.00 |
Between-group comparisonsa | – | 0.0431 | 0.0695 | 0.0957 |
BREEZE-AD2 | ||||
Sample size | 85 | 163 | 263 | 23 |
Mean (SD) at baseline | − 1.63 (1.604) | − 1.36 (2.434) | − 0.70 (1.655) | − 0.43 (1.183) |
Median change | − 1.14 | − 0.86 | − 0.45 | − 0.29 |
Between-group comparisonsa | – | 0.2260 | 0.0004 | 0.6256 |
BREEZE-AD5 | ||||
Sample size | 49 | 104 | 176 | 8 |
Mean (SD) at baseline | − 2.16 (1.665) | − 1.55 (2.631) | − 0.51 (1.526) | 0.24 (0.592) |
Median change | − 1.86 | − 0.86 | − 0.43 | 0.00 |
Between-group comparisonsa | – | 0.0753 | 0.0001 | 0.2183 |
ADSS item 3 | ||||
BREEZE-AD1 | ||||
Sample size | 22 | 71 | 162 | 10 |
Mean (SD) change | − 1.00 (0.916) | − 0.77 (0.981) | − 0.32 (0.868) | 0.70 (1.023) |
Median change | − 0.98 | − 0.71 | − 0.23 | 0.65 |
Between-group comparisonsa | – | 0.2873 | 0.0011 | 0.0005 |
BREEZE-AD2 | ||||
Sample size | 9 | 51 | 141 | 10 |
Mean (SD) at baseline | − 1.11 (0.906) | − 0.76 (0.869) | − 0.22 (0.940) | 0.43 (0.838) |
Median change | − 1.25 | − 0.80 | − 0.17 | 0.50 |
Between-group comparisonsa | – | 0.3592 | 0.0003 | 0.0574 |
BREEZE-AD5 | ||||
Sample size | 15 | 52 | 115 | 2 |
Mean (SD) at baseline | − 1.60 (0.951) | − 1.27 (1.021) | − 0.18 (0.794) | − 0.79 (1.111) |
Median change | − 1.86 | − 1.14 | 0.00 | − 0.79 |
Between-group comparisonsa | – | 0.4839 | < 0.0001 | 0.2654 |
POEM groups at week 4 | ||||
---|---|---|---|---|
Much Improved (> 1 Category Improvement) | Improved (1 Category Improvement) | Stable (No Category Change) | Declined (≥ 1 Category Worsening) | |
Itch NRS | ||||
BREEZE-AD1 | ||||
Sample
size | 63 | 191 | 301 | 26 |
Mean (SD) change | − 3.85 (1.943) | − 2.29 (1.779) | − 1.07 (1.629) | 0.21 (1.942) |
Median change | − 3.67 | − 2.14 | − 0.86 | 0.64 |
Between-group comparisonsa | – | < 0.0001 | < 0.0001 | 0.0002 |
BREEZE-AD2 | ||||
Sample size | 69 | 190 | 286 | 23 |
Mean (SD) at baseline | − 3.90 (2.318) | − 2.45 (2.101) | − 1.08 (1.634) | 0.14 (1.049) |
Median change | − 3.71 | − 2.29 | − 0.86 | 0.17 |
Between-group comparisonsa | – | < 0.0001 | < 0.0001 | 0.0030 |
BREEZE-AD5 | ||||
Sample size | 35 | 114 | 217 | 13 |
Mean (SD) at baseline | − 4.12 (2.261) | − 2.56 (2.059) | − 1.15 (1.627) | − 0.81 (1.569) |
Median change | − 3.71 | − 2.30 | − 0.86 | − 0.57 |
Between-group comparisonsa | – | 0.0002 | < 0.0001 | 0.9320 |
Skin pain NRS | ||||
BREEZE-AD1 | ||||
Sample size | 63 | 191 | 301 | 26 |
Mean (SD) change | − 3.49 (2.111) | − 2.24 (1.970) | − 0.97 (1.773) | 0.31 (1.726) |
Median change | − 3.14 | − 1.86 | − 0.71 | 0.48 |
Between-group comparisonsa | – | < 0.0001 | < 0.0001 | 0.0007 |
BREEZE-AD2 | ||||
Sample size | 69 | 190 | 286 | 23 |
Mean (SD) at baseline | − 4.13 (2.412) | − 2.66 (2.290) | − 0.97 (1.826) | 0.20 (1.206) |
Median change | − 4.00 | − 2.29 | − 0.86 | 0.43 |
Between-group comparisonsa | – | < 0.0001 | < 0.0001 | 0.0118 |
BREEZE-AD5 | ||||
Sample size | 35 | 114 | 217 | 13 |
Mean (SD) at baseline | − 4.24 (2.361) | − 2.49 (2.119) | − 1.19 (1.889) | − 0.38 (1.667) |
Median change | − 4.00 | − 2.15 | − 0.90 | − 0.57 |
Between-group comparisonsa | – | < 0.0001 | < 0.0001 | 0.3379 |
ADSS item 1 | ||||
BREEZE-AD1 | ||||
Sample size | 63 | 191 | 301 | 26 |
Mean (SD) change | − 1.31 (0.958) | − 0.75 (0.828) | − 0.42 (0.813) | 0.31 (1.061) |
Median change | − 1.29 | − 0.71 | − 0.29 | 0.00 |
Between-group comparisonsa | – | < 0.0001 | < 0.0001 | < 0.0001 |
BREEZE-AD2 | ||||
Sample size | 69 | 190 | 286 | 23 |
Mean (SD) at baseline | − 1.30 (0.886) | − 0.85 (0.894) | − 0.35 (0.823) | 0.20 (0.507) |
Median change | − 1.14 | − 0.71 | − 0.31 | 0.14 |
Between-group comparisonsa | – | 0.0001 | < 0.0001 | 0.0062 |
BREEZE-AD5 | ||||
Sample size | 35 | 114 | 217 | 13 |
Mean (SD) at baseline | − 1.49 (0.918) | − 0.88 (0.839) | − 0.46 (0.814) | − 0.12 (0.787) |
Median change | − 1.43 | − 0.88 | − 0.29 | 0.00 |
Between-group comparisonsa | – | 0.0014 | < 0.0001 | 0.2903 |
ADSS item 2 | ||||
BREEZE-AD1 | ||||
Sample size | 63 | 191 | 301 | 26 |
Mean (SD) change | − 1.85 (2.836) | − 1.45 (3.027) | − 0.70 (2.119) | 0.35 (2.133) |
Median change | − 1.00 | − 0.71 | − 0.43 | 0.15 |
Between-group comparisonsa | – | 0.2945 | 0.0019 | 0.0375 |
BREEZE-AD2 | ||||
Sample size | 69 | 190 | 286 | 23 |
Mean (SD) at baseline | − 1.34 (1.490) | − 1.12 (2.629) | − 0.52 (2.105) | 0.12 (0.601) |
Median change | − 0.86 | − 0.56 | − 0.43 | 0.00 |
Between-group comparisonsa | – | 0.3931 | 0.0096 | 0.1092 |
BREEZE-AD5 | ||||
Sample size | 35 | 114 | 217 | 13 |
Mean (SD) at baseline | − 1.66 (1.522) | − 1.13 (1.365) | − 0.54 (1.208) | 0.06 (0.791) |
Median change | − 1.29 | − 0.67 | − 0.31 | 0.29 |
Between-group comparisonsa | – | 0.1450 | 0.0001 | 0.1491 |
ADSS item 3 | ||||
BREEZE-AD1 | ||||
Sample size | 20 | 80 | 201 | 9 |
Mean (SD) change | − 1.15 (1.024) | − 0.73 (0.833) | − 0.31 (0.807) | 0.27 (0.843) |
Median change | − 1.21 | − 0.66 | − 0.20 | 0.29 |
Between-group comparisonsa | – | 0.0468 | 0.0002 | 0.0500 |
BREEZE-AD2 | ||||
Sample size | 19 | 72 | 165 | 13 |
Mean (SD) at baseline | − 1.27 (0.700) | − 0.70 (0.814) | − 0.24 (0.849) | 0.05 (0.472) |
Median change | − 1.26 | − 0.60 | − 0.29 | 0.00 |
Between-group comparisonsa | – | 0.0069 | < 0.0001 | 0.2670 |
BREEZE-AD5 | ||||
Sample size | 14 | 48 | 138 | 7 |
Mean (SD) at baseline | − 1.54 (0.856) | − 1.05 (0.739) | − 0.41 (0.749) | − 0.47 (1.075) |
Median change | − 1.38 | − 1.00 | − 0.36 | − 0.29 |
Between-group comparisonsa | – | 0.1086 | < 0.0001 | 0.6526 |
Meaningful change estimation
Anchor-based
Estimate (%) | Scale | BREEZE-AD1 | BREEZE-AD2 | BREEZE-AD5 | Overall | Final MCT | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Measure | MCT min | MCT mod | MCT large | MCT min | MCT mod | MCT large | MCT min | MCT mod | MCT large | MCT min | MCT mod | MCT large | ||
Itch NRS | 0–10 | − 2.25 | − 4.00 | − 6.00 | − 2.25 | − 4.50 | − 6.00 | − 2.50 | − 4.50 | − 7.00 | − 2.25 | − 4.25 | − 6.50 | − 4.00 |
Skin Pain NRS | 0–10 | − 2.00 | − 4.00 | − 6.00 | − 2.25 | − 4.50 | − 6.00 | − 3.00 | − 4.00 | − 7.00 | − 2.25 | − 4.00 | − 6.50 | − 4.00 |
ADSS Item 1 | 0–4 | − 0.75 | − 1.25 | − 2.00 | − 0.75 | − 1.25 | − 1.75 | − 0.75 | − 1.50 | − 2.25 | − 0.75 | − 1.25 | − 2.00 | − 1.25 |
ADSS Item 2 | 0–29 | − 1.00 | − 1.75 | − 3.00 | − 0.75 | − 1.50 | − 2.00 | − 1.00 | − 1.50 | − 3.00 | − 1.00 | − 1.50 | − 3.00 | − 1.50 |
ADSS Item 3 | 0–4 | − 0.50 | − 1.25 | − 2.00 | − 0.50 | − 1.25 | − 1.50 | − 1.00 | − 1.75 | − 2.50 | − 0.75 | − 1.25 | − 2.00 | − 1.25 |
Distribution-based
Measure | Study | Distribution-based estimates | |||
---|---|---|---|---|---|
0.2 SD | 0.5 SD | 0.8 SD | SEM | ||
Itch NRS (scale 0–10) | BREEZE-AD1 | 0.42 | 1.04 | 1.67 | 0.88 |
BREEZE-AD2 | 0.43 | 1.09 | 1.74 | 0.89 | |
BREEZE-AD5 | 0.43 | 1.09 | 1.74 | 0.92 | |
Overall | 0.43 | 1.07 | 1.72 | 0.89 | |
Skin pain NRS (scale 0–10) | BREEZE-AD1 | 0.49 | 1.23 | 1.98 | 1.09 |
BREEZE-AD2 | 0.51 | 1.27 | 2.04 | 1.06 | |
BREEZE-AD5 | 0.53 | 1.32 | 2.11 | 1.20 | |
Overall | 0.51 | 1.27 | 2.04 | 1.12 | |
ADSS item 1 (scale 0–4) | BREEZE-AD1 | 0.22 | 0.54 | 0.86 | 0.49 |
BREEZE-AD2 | 0.22 | 0.56 | 0.90 | 0.49 | |
BREEZE-AD5 | 0.24 | 0.60 | 0.95 | 0.52 | |
Overall | 0.23 | 0.57 | 0.90 | 0.50 | |
ADSS item 2 (scale 0–29) | BREEZE-AD1 | 0.93 | 2.34 | 3.74 | 1.39 |
BREEZE-AD2 | 0.46 | 1.15 | 1.85 | 1.31 | |
BREEZE-AD5 | 0.58 | 1.45 | 2.32 | 0.82 | |
Overall | 0.66 | 1.65 | 2.64 | 1.17 | |
ADSS item 3 (scale 0–4) | BREEZE-AD1 | 0.19 | 0.47 | 0.76 | 0.48 |
BREEZE-AD2 | 0.19 | 0.49 | 0.78 | 0.52 | |
BREEZE-AD5 | 0.19 | 0.47 | 0.76 | 0.51 | |
Overall | 0.19 | 0.48 | 0.77 | 0.50 |