Table 2.
Clinical outcomes by study quarter for the overall population, and in subgroups with and without previous cystic fibrosis transmembrane conductance regulator modulator therapy.
| N (change) | Mean ± SD | Change (95% CI)a | p-valueb | |
|---|---|---|---|---|
| Total population | ||||
| ppFEV1 | ||||
| Previous 10–12 months | 1674 (1494) | 65.3 ± 24.1 | −0.4 (−0.8, 0.0) | 0.0758 |
| Baseline | 2291 (−) | 64.6 ± 24.0 | – | – |
| ETI therapy 1–3 months | 2155 (1937) | 75.9 ± 25.0 | 11.3 (10.8, 11.7) | <0.0001 |
| ETI therapy 4–6 months | 1993 (1788) | 76.1 ± 24.5 | 11.6 (11.1, 12.1) | <0.0001 |
| ETI therapy 7–9 months | 1875 (1685) | 75.9 ± 24.5 | 11.7 (11.2, 12.3) | <0.0001 |
| ETI therapy 10–12 months | 1863 (1667) | 76.3 ± 24.6 | 11.3 (10.8, 11.8) | <0.0001 |
| BMI (adults), kg/m2 | ||||
| Previous 10–12 months | 1329 (1207) | 21.2 ± 3.0 | 0.1 (0.1, 0.2) | <0.0001 |
| Baseline | 1826 (−) | 21.4 ± 3.2 | – | – |
| ETI therapy 1–3 months | 1684 (1541) | 22.1 ± 3.2 | 0.7 (0.7, 0.8) | <0.0001 |
| ETI therapy 4–6 months | 1566 (1437) | 22.6 ± 3.3 | 1.2 (1.1, 1.3) | <0.0001 |
| ETI therapy 7–9 months | 1507 (1379) | 22.7 ± 3.2 | 1.3 (1.2, 1.4) | <0.0001 |
| ETI therapy 10–12 months | 1478 (1349) | 22.8 ± 3.2 | 1.4 (1.3, 1.4) | <0.0001 |
| BMI z-score (adolescents) | ||||
| Previous 10–12 months | 448 (416) | −0.5 ± 1.0 | 0.0 (0.0, 0.1) | 0.0819 |
| Baseline | 564 (−) | −0.5 ± 1.1 | – | – |
| ETI therapy 1–3 months | 538 (504) | −0.3 ± 0.9 | 0.3 (0.2, 0.3) | <0.0001 |
| ETI therapy 4–6 months | 501 (459) | −0.2 ± 1.0 | 0.3 (0.3, 0.4) | <0.0001 |
| ETI therapy 7–9 months | 460 (428) | −0.2 ± 1.0 | 0.4 (0.3, 0.4) | <0.0001 |
| ETI therapy 10–12 months | 474 (436) | −0.2 ± 1.0 | 0.3 (0.3, 0.4) | <0.0001 |
| Exacerbations | ||||
| Previous 10–12 months | 2645 (−) | 464 | −19 | 0.0326 |
| Baseline | 2645 (−) | 483 | – | – |
| ETI therapy 1–3 months | 2645 (−) | 146 | −337 | <0.0001 |
| ETI therapy 4–6 months | 2645 (−) | 95 | −388 | <0.0001 |
| ETI therapy 7–9 months | 2645 (−) | 107 | −376 | <0.0001 |
| ETI therapy 10–12 months | 2645 (−) | 145 | −338 | <0.0001 |
| Cftr modulator naïve population | ||||
| ppFEV1 | ||||
| Previous 10–12 months | 854 (753) | 68.6 ± 23.9 | −0.9 (−1.5, −0.3) | 0.0051 |
| Baseline | 1249 (−) | 66.6 ± 24.1 | – | – |
| ETI therapy 1–3 months | 1183 (1064) | 79.2 ± 24.8 | 12.6 (11.9, 13.2) | <0.0001 |
| ETI therapy 4–6 months | 1067 (961) | 79.5 ± 24.2 | 13.1 (12.4, 13.8) | <0.0001 |
| ETI therapy 7–9 months | 1022 (921) | 78.6 ± 24.4 | 12.9 (12.2, 13.7) | <0.0001 |
| ETI therapy 10–12 months | 1007 (903) | 79.6 ± 24.3 | 12.6 (11.9, 13.4) | <0.0001 |
| BMI (adults), kg/m2 | ||||
| Previous 10–12 months | 629 (567) | 21.4 ± 3.0 | 0.1 (−0.0, 0.2) | 0.1007 |
| Baseline | 948 (−) | 21.6 ± 3.2 | – | – |
| ETI therapy 1–3 months | 880 (807) | 22.3 ± 3.2 | 0.7 (0.7, 0.8) | <0.0001 |
| ETI therapy 4–6 months | 785 (724) | 22.7 ± 3.3 | 1.2 (1.1, 1.3) | <0.0001 |
| ETI therapy 7–9 months | 779 (715) | 22.8 ± 3.2 | 1.3 (1.2, 1.4) | <0.0001 |
| ETI therapy 10–12 months | 757 (690) | 22.9 ± 3.2 | 1.3 (1.2, 1.5) | <0.0001 |
| BMI z-score (adolescents) | ||||
| Previous 10–12 months | 272 (252) | −0.6 ± 1.0 | 0.0 (−0.0, 0,1) | 0.2306 |
| Baseline | 352 (−) | −0.6 ± 1.1 | – | – |
| ETI therapy 1–3 months | 335 (312) | −0.3 ± 1.0 | 0.3 (0.3, 0.3) | <0.0001 |
| ETI therapy 4–6 months | 316 (292) | −0.3 ± 1.0 | 0.4 (0.3, 0.4) | <0.0001 |
| ETI therapy 7–9 months | 287 (266) | −0.2 ± 1.0 | 0.4 (0.4, 0.5) | <0.0001 |
| ETI therapy 10–12 months | 297 (274) | −0.2 ± 1.0 | 0.4 (0.4, 0.5) | <0.0001 |
| Exacerbations | ||||
| Previous 10–12 months | 1439 (−) | 229 | −48 | 0.0002 |
| Baseline | 1439 (−) | 277 | – | – |
| ETI therapy 1–3 months | 1439 (−) | 79 | −198 | <0.0001 |
| ETI therapy 4–6 months | 1439 (−) | 50 | −227 | <0.0001 |
| ETI therapy 7–9 months | 1439 (−) | 54 | −223 | <0.0001 |
| ETI therapy 10–12 months | 1439 (−) | 78 | −199 | <0.0001 |
| Previous cftr modulator use population | ||||
| ppFEV1 | ||||
| Previous 10–12 months | 820 (741) | 61.8 ± 23.7 | 0.1 (−0.5, 0.7) | 0.7279 |
| Baseline | 1042 (−) | 62.2 ± 23.7 | – | – |
| ETI therapy 1–3 months | 972 (873) | 72.0 ± 24.7 | 9.6 (9.0, 10.3) | <0.0001 |
| ETI therapy 4–6 months | 926 (827) | 72.1 ± 24.2 | 9.9 (9.2, 10.5) | <0.0001 |
| ETI therapy 7–9 months | 853 (764) | 72.6 ± 24.3 | 10.3 (9.6, 11.0) | <0.0001 |
| ETI therapy 10–12 months | 856 (764) | 72.4 ± 24.4 | 9.7 (9.0, 10.5) | <0.0001 |
| BMI (adults), kg/m2 | ||||
| Previous 10–12 months | 700 (640) | 21.1 ± 3.0 | 0.2 (0.1, 0.3) | <0.0001 |
| Baseline | 878 (−) | 21.3 ± 3.2 | – | – |
| ETI therapy 1–3 months | 804 (734) | 22.0 ± 3.2 | 0.8 (0.7, 0.8) | <0.0001 |
| ETI therapy 4–6 months | 781 (713) | 22.4 ± 3.3 | 1.2 (1.1, 1.3) | <0.0001 |
| ETI therapy 7–9 months | 728 (664) | 22.5 ± 3.2 | 1.3 (1.2, 1.5) | <0.0001 |
| ETI therapy 10–12 months | 721 (659) | 22.6 ± 3.3 | 1.4 (1.2, 1.5) | <0.0001 |
| BMI z-score (adolescents) | ||||
| Previous 10–12 months | 176 (164) | −0.5 ± 0.9 | 0.0 (−0.0, 0.11) | 0.1989 |
| Baseline | 212 (−) | −0.4 ± 0.9 | – | – |
| ETI therapy 1–3 months | 203 (192) | −0.2 ± 0.9 | 0.2 (0.1, 0.3) | <0.0001 |
| ETI therapy 4–6 months | 185 (167) | −0.2 ± 0.9 | 0.3 (0.2, 0.4) | <0.0001 |
| ETI therapy 7–9 months | 173 (162) | −0.2 ± 0.9 | 0.2 (0.1, 0.3) | <0.0001 |
| ETI therapy 10–12 months | 177 (162) | −0.2 ± 0.9 | 0.2 (0.1, 0.3) | <0.0001 |
| Exacerbations | ||||
| Previous 10–12 months | 1206 (−) | 235 | 29 | 0.0002 |
| Baseline | 1206 (−) | 206 | – | – |
| ETI therapy 1–3 months | 1206 (−) | 67 | −139 | <0.0001 |
| ETI therapy 4–6 months | 1206 (−) | 45 | −161 | <0.0001 |
| ETI therapy 7–9 months | 1206 (−) | 53 | −153 | <0.0001 |
| ETI therapy 10–12 months | 1206 (−) | 67 | −139 | <0.0001 |
BMI, body mass index; CI, confidence interval; ETI, elexacaftor/tezacaftor/ivacaftor; ppFEV1, percent predicted forced expiratory volume in 1 s; SD, standard deviation.
a
Change is calculated as mean minus baseline mean except for the ‘Previous 10–12 months’ rows where change is calculated as baseline minus the mean for the 10–12 months before starting ETI.
b
p-values were calculated using paired t-test for ppFEV1, BMI and BMI z-score, and McNemar's test for exacerbations. All p-values and were corrected using the Benjamini-Hochberg method.