Table 3.
Efficacy: Change in TNSS at Week 17
| Primary Endpoint | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| % Change in TNSS AUC (0–1 h) for SCIT+dupilumab vs SCIT (MI, primary analysis) LS mean difference (95% CI) | 4.73 (−21.023, 30.487) | ||||||||
| P value | 0.7185 | ||||||||
| Placebo (n =25) | Dupilumab (n = 26) | SCIT (n = 26) | SCIT+dupilumab (n = 26) | SCIT+dupilumab vs SCIT | Dupilumab vs Placebo | SCIT+dupilumab vs Dupilumab | SCIT vs Placebo | SCIT+dupilumab vs Placebo | |
| LS Mean (SE) | LS Mean Difference (95% CI) | ||||||||
| Secondary Endpoints | Pre-Specified Analyses | Post Hoc Analyses | |||||||
| % Change in TNSS AUC (0–1 h) (MI, primary analysis) | −28.82 (8.427) | −21.57 (8.415) | −56.76 (9.687) | −52.03 (8.462) |
7.25 (−16.028, 30.530) |
−30.45 (−53.874, −7.034) |
−27.94 (−52.98, −2.886) |
−23.20 (−46.691, 0.284) |
|
| P value | 0.5416 | 0.0108 | 0.0289 | 0.0528 | |||||
| % Change in TNSS AUC (0–1 h) (LOCF, sensitivity analysis) | −27.6 (8.74) | −18.4 (8.53) | −43.9 (8.55) | −52.3 (8.54) |
−8.3 (−32.26, 15.61) |
9.2 (−14.97, 33.45) |
−33.9 (−57.84, −9.88) |
−16.3 (−40.64, 8.05) |
−24.6 (−48.96, −0.29) |
| P value | 0.4916 | 0.4508 | 0.0061 | 0.1871 | 0.0474 | ||||
| % Change in TNSS AUC (0–1 h) (OC, sensitivity analysis) | (n = 24) −28.8 (8.60) |
(n = 24) −20.3 (8.57) |
(n = 18) −59.3 (9.90) |
(n = 24) −53.2 (8.58) |
6.1 (−19.88, 32.15) |
8.5 (−15.63, 32.60) |
−32.9 (−56.98, −8.75) |
−30.5 (−56.64, −4.39) |
−24.4 (−48.59, −0.17) |
| P value | 0.6404 | 0.4862 | 0.0081 | 0.0226 | 0.0484 | ||||
| Absolute change in TNSS AUC (0–1 h) (MI) | −1.85 (0.323) | −1.83 (0.329) | −3.07 (0.361) | −2.77 (0.321) | 0.30 (−0.661, 1.254) |
0.03 (−0.877, 0.928) |
−0.94 (−1.848, −0.037) |
−1.21 (−2.160, −0.266) |
−0.92 (−1.812, −0.022) |
| P value | 0.5438 | 0.9559 | 0.0414 | 0.0121 | 0.0446 | ||||
| Absolute change in TNSS AUC (0–1 h) (LOCF) | −1.74 (0.384) | −1.63 (0.375) | −2.27 (0.376) | −2.62 (0.375) | −0.34 (−1.393, 0.710) |
0.11 (−0.950, 1.177) |
−0.99 (−2.042, 0.065) |
−0.53 (−1.602, 0.537) |
−0.87 (−1.943, 0.195) |
| P value | 0.5203 | 0.8324 | 0.0656 | 0.3255 | 0.1077 | ||||
| Absolute change in TNSS AUC (0–1 h) (OC) | (n = 24) −1.83 (0.331) |
(n = 24) −1.80 (0.330) |
(n = 18) −3.08 (0.381) |
(n = 24) −2.75 (0.330) | 0.33 (−0.670, 1.334) |
0.03 (−0.896, 0.961) |
−0.95 (−1.879, −0.022) |
−1.25 (−2.256, −0.244) |
−0.92 (−1.851, −0.014) |
| P value | 0.5120 | 0.9448 | 0.0449 | 0.0155 | 0.0535 | ||||
| Exploratory Endpoints | Pre-Specified Analyses | Post Hoc Analyses | |||||||
| % Change in peak TNSS (MI) | −16.14 (6.773) | −29.91 (6.765) | −34.29 (7.760) | −39.62 (6.646) | −5.33 (−25.771, 15.113) |
−13.76 (−32.649, 5.120) |
−9.71 (−28.379, 8.960) |
−18.14 (−38.513, 2.223) |
−23.47 (−42.060, −4.887) |
| P value | 0.6090 | 0.1531 | 0.3080 | 0.0808 | 0.0133 | ||||
| % Change in peak TNSS (LOCF) | −16.4 (7.01) | −26.3 (6.74) | −29.4 (6.80) | −40.7 (6.72) | −11.2 (−30.22, 7.76) |
−9.9 (−29.31, 9.53) |
−14.4 (−33.25, 4.54) |
−13.0 (−32.70, 6.65) |
−24.3 (−43.51, −5.00) |
| P value | 0.2434 | 0.3145 | 0.1348 | 0.1921 | 0.0141 | ||||
| % Change in peak TNSS (OC) | (n = 24) −16.5 (6.89) |
(n = 24) −29.7 (6.81) |
(n = 18) −35.0 (7.87) |
(n = 24) −40.4 (6.77) |
−5.4 (−26.06, 15.25) |
−13.2 (−32.63, 6.23) |
−10.7 (−29.77, 8.43) |
−18.5 (−39.47, 2.55) |
−23.9 (−43.06, −4.68) |
| P value | 0.6042 | 0.1804 | 0.2698 | 0.0842 | 0.0154 | ||||
| Absolute change in peak TNSS (MI) | −1.6 (0.58) | −3.0 (0.58) | −3.1 (0.65) | −3.4 (0.57) | −0.4 (−2.08, 1.36) |
−1.4 (−3.01, 0.23) |
−0.5 (−2.07, 1.12) |
−1.5 (−3.23, 0.22) |
−1.9 (−3.45, −0.28) |
| P value | 0.6805 | 0.0929 | 0.5603 | 0.0871 | 0.0212 | ||||
| Absolute change in peak TNSS (LOCF) | −1.6 (0.60) | −2.6 (0.58) | −2.6 (0.58) | −3.4 (0.58) | −0.8 (−2.48, 0.78) |
−1.1 (−2.72, 0.61) |
−0.8 (−2.45, 0.80) |
−1.0 (−2.72, 0.65) |
−1.9 (−3.53, −0.23) |
| P value | 0.3060 | 0.2117 | 0.3153 | 0.2266 | 0.0262 | ||||
| Absolute change in peak TNSS (OC) | (n = 24) −1.6 (0.59) |
(n = 24) −3.0 (0.58) |
(n = 18) −3.1 (0.67) |
(n = 24) −3.5 (0.58) |
−0.3 (−2.11, 1.43) |
−1.4 (−3.03, 0.30) |
−0.5 (−2.13, 1.14) |
−1.5 (−3.32, 0.28) |
−1.9 (−3.51, −0.22) |
| P value | 0.7001 | 0.1061 | 0.5484 | 0.0970 | 0.0268 | ||||
Abbreviations: AUC, area under the curve; CI, confidence interval; LOCF, last observation carried forward; LS, least squares; MI, multiple imputation; OC, observed values; SCIT, subcutaneous immunotherapy; SE, standard error; TNSS, total nasal symptom score.