In a randomized, placebo-controlled, phase III clinical trial, adolescents with moderate-to-severe atopic dermatitis (AD) receiving dupilumab showed significant improvements in clinical signs as demonstrated by Investigator’s Global Assessment (IGA) score reflecting clear (0)/almost clear (1) skin at week 16; however, the IGA may not comprehensively capture the impact of AD, including patient-reported symptoms and health-related quality of life. |
The majority of adolescents treated with dupilumab showed statistically significant and clinically meaningful improvements in AD signs, symptoms (including pruritus, sleep loss), and quality of life compared with placebo-treated patients, even among those not achieving IGA 0/1. |
The IGA response should be interpreted within the context of additional outcome measures that more comprehensively characterize changes with treatment in AD signs, symptoms, and quality of life in adolescents with moderate-to-severe disease. |
1 Introduction
2 Patients and Methods
2.1 Study Design
2.2 Patients, Randomization, and Masking
2.3 Study Outcomes
2.4 Statistical Analysis
3 Results
3.1 Patients
Full analysis set (n = 251) | IGA > 1 subgroup (n = 214) | |||||
---|---|---|---|---|---|---|
Placebo (n = 85) | Dupilumab 300 mg q4w (n = 84) | Dupilumab 200 or 300 mg q2w (n = 82) | Placebo (n = 83) | Dupilumab 300 mg q4w (n = 69) | Dupilumab 200 or 300 mg q2w (n = 62) | |
Age, mean (SD), years | 14.5 (1.8) | 14.4 (1.6) | 14.5 (1.7) | 14.4 (1.8) | 14.3 (1.5) | 14.6 (1.7) |
Male, n (%) | 53 (62) | 52 (62) | 43 (52) | 51 (61) | 44 (64) | 30 (48) |
Weight, mean (SD), kg | 64.4 (21.5) | 65.8 (20.1) | 65.6 (24.5) | 64.0 (21.1) | 66.3 (20.5) | 65.9 (20.6) |
BMI, mean (SD), kg/m2 | 23.9 (6.0) | 24.1 (5.9) | 24.9 (7.9) | 23.9 (6.1) | 24.1 (5.9) | 24.9 (6.2) |
Race, n (%) | ||||||
White | 48 (56) | 55 (65) | 54 (66) | 47 (57) | 44 (64) | 41 (66) |
Black or African American | 15 (18) | 8 (10) | 7 (9) | 14 (17) | 6 (9) | 3 (5) |
Asian | 13 (15) | 13 (15) | 12 (15) | 13 (16) | 11 (16) | 10 (16) |
American Indian or Alaska Native | 0 | 2 (2) | 0 | 0 | 2 (3) | 0 |
Native Hawaiian or other Pacific Islander | 0 | 1 (1) | 2 (2) | 0 | 1 (1) | 1 (2) |
Other | 6 (7) | 5 (6) | 5 (6) | 6 (7) | 5 (7) | 5 (8) |
Not reported | 3 (4) | 0 | 2 (2) | 3 (4) | 0 | 2 (3) |
Ethnicity, n (%) | ||||||
Hispanic or Latino | 13 (15) | 20 (24) | 13 (16) | 13 (16) | 14 (20) | 11 (18) |
Duration of AD, mean (SD), years | 12.3 (3.4) | 11.9 (3.2) | 12.5 (3.0) | 12.2 (3.5) | 12.1 (3.1) | 12.5 (3.0) |
History of atopic comorbidities, n (%) | ||||||
Patients with ≥ 1 concurrent allergic condition excluding AD | 78 (92) | 74 (88) | 79 (96) | 76 (92) | 61 (88) | 61 (98) |
Allergic conjunctivitis (keratoconjunctivitis) | 16 (19) | 21 (25) | 20 (24) | 15 (18) | 20 (29) | 15 (24) |
Allergic rhinitis | 57 (67) | 49 (58) | 59 (72) | 55 (66) | 38 (55) | 44 (71) |
Asthma | 46 (54) | 43 (51) | 46 (56) | 44 (53) | 37 (54) | 34 (55) |
Chronic rhinosinusitis | 7 (8) | 6 (7) | 6 (7) | 7 (8) | 5 (7) | 4 (6) |
Eosinophilic esophagitis | 0 | 0 | 1 (1) | 0 | 0 | 0 |
Food allergy | 48 (57) | 53 (63) | 52 (63) | 46 (55) | 43 (62) | 42 (68) |
Hives | 22 (26) | 28 (33) | 22 (27) | 22 (27) | 23 (33) | 20 (32) |
Nasal polyps | 2 (2) | 1 (1) | 2 (2) | 2 (2) | 0 | 2 (3) |
Other allergiesa | 62 (73) | 54 (64) | 58 (71) | 61 (73) | 49 (71) | 46 (74) |
Patients receiving prior systemic medications for AD, n (%) | 33 (39) | 38 (45) | 35 (43) | 32 (39) | 31 (45) | 27 (44) |
Systemic corticosteroids | 21 (25) | 27 (32) | 21 (26) | 20 (24) | 20 (29) | 15 (24) |
Systemic nonsteroidal immunosuppressants | 17 (20) | 15 (18) | 20 (24) | 17 (20) | 15 (22) | 16 (26) |
Azathioprine | 1 (1) | 1 (1) | 0 | 1 (1) | 1 (1) | 0 |
Cyclosporine | 12 (14) | 6 (7) | 14 (17) | 12 (14) | 6 (9) | 13 (21) |
Methotrexate | 6 (7) | 10 (12) | 10 (12) | 6 (7) | 10 (14) | 7 (11) |
Mycophenolate | 0 | 1 (1) | 2 (2) | 0 | 1 (1) | 1 (2) |
Biomarkers, mean (SD) | ||||||
Lactate dehydrogenase, U/L | 286.0 (99.1) | 300.9 (101.6) | 295.4 (102.5) | 286.4 (100.2) | 315.3 (101.8) | 311.3 (109.0) |
Total IgE, kU/L | 9378.9 (13,797.2) | 7032.1 (9215.0) | 7254.5 (9457.1) | 9427.7 (13,929.7) | 7787.8 (9625.9) | 8371.3 (9967.8) |
TARC, pg/mL | 6565.8 (11,296.5) | 5781.9 (8369.0) | 6102.3 (9159.6) | 6676.7 (11,410.6) | 6349.4 (8796.9) | 7272.2 (10,097.1) |
Disease severity, mean (SD) unless otherwise noted | ||||||
IGA score 4, n (%) | 46 (54) | 46 (55) | 43 (52) | 45 (54) | 44 (64) | 35 (56) |
EASI (0–72) | 35.5 (14.0) | 35.8 (14.8) | 35.3 (13.8) | 35.4 (13.9) | 37.8 (14.7) | 37.5 (14.4) |
SCORAD total score (0–103) | 70.4 (13.3) | 69.8 (14.1) | 70.6 (13.9) | 70.3 (13.3) | 71.7 (14.0) | 72.5 (14.0) |
BSA affected by AD (%) | 56.4 (24.1) | 56.9 (23.5) | 56.0 (21.4) | 56.4 (24.4) | 58.6 (23.5) | 59.4 (22.4) |
Peak Pruritus NRS score (0–10) | 7.7 (1.6) | 7.5 (1.8) | 7.5 (1.5) | 7.7 (1.6) | 7.8 (1.7) | 7.6 (1.4) |
SCORAD—Pruritus VAS score (0–10) | 7.7 (1.8) | 7.9 (1.9) | 7.9 (1.7) | 7.7 (1.8) | 7.9 (1.9) | 8.0 (1.5) |
SCORAD—Sleep VAS score (0–10) | 5.6 (3.1) | 5.9 (3.2) | 5.4 (3.3) | 5.6 (3.1) | 6.3 (3.1) | 5.8 (3.4) |
POEM score (0–28) | 21.1 (5.4) | 21.1 (5.5) | 21.0 (5.0) | 21.0 (5.4) | 21.6 (5.6) | 21.5 (5.1) |
CDLQI (0–30) | 13.1 (6.7) | 14.8 (7.4) | 13.0 (6.2) | 13.0 (6.7) | 15.4 (7.5) | 14.3 (6.1) |
HADS total score (0–42) | 11.6 (7.8) | 13.3 (8.2) | 12.6 (8.0) | 11.7 (7.8) | 13.5 (8.2) | 12.9 (8.5) |
HADS-A score (0–21) | 7.4 (4.4) | 8.0 (4.9) | 8.1 (4.6) | 7.4 (4.4) | 8.1 (4.9) | 8.2 (4.8) |
HADS-D score (0–21) | 4.3 (3.9) | 5.2 (4.2) | 4.4 (4.2) | 4.3 (3.9) | 5.3 (4.2) | 4.7 (4.4) |
PGADS “no” or “mild” symptoms, n (%) | 10 (12) | 5 (6) | 8 (10) | 10 (12) | 2 (3) | 4 (6) |
PGADS “moderate” symptoms, n (%) | 20 (23.5) | 32 (38) | 22 (27) | 20 (24) | 23 (33) | 16 (26) |
PGADS “severe” symptoms, n (%) | 30 (35) | 26 (31) | 32 (39) | 28 (34) | 23 (33) | 27 (44) |
PGADS “very severe” symptoms, n (%) | 25 (29) | 21 (25) | 20 (24) | 25 (30) | 21 (30) | 15 (24) |
3.2 Clinician- and Patient-Reported Outcomes
3.2.1 Full Analysis Set of Randomized Patients
Full analysis set (n = 251) | IGA > 1 subgroup (n = 214) | |||||
---|---|---|---|---|---|---|
Placebo (n = 85) | Dupilumab 300 mg q4w (n = 84) | Dupilumab 200 or 300 mg q2w (n = 82) | Placebo (n = 83) | Dupilumab 300 mg q4w (n = 69) | Dupilumab 200 or 300 mg q2w (n = 62) | |
EASI LS mean change from baseline (SE) | − 9.2 (1.8) | − 22.6 (1.5) p < 0.0001 | − 22.2 (1.3) p < 0.0001 | − 8.8 (1.9) | − 21.9 (1.7) p < 0.0001 | − 19.7 (1.6) p < 0.0001 |
EASI LS mean percent change from baseline (SE) | − 23.6 (5.5) | − 64.8 (4.5) p < 0.0001 | − 65.9 (4.0) p < 0.0001 | −20.7 (5.6) | − 58.4 (5.5) p < 0.0001 | − 55.0 (4.9) p < 0.0001 |
EASI-50, n (%) | 11 (13) | 46 (55) p < 0.0001 | 50 (61) p < 0.0001 | 9 (11) | 31 (45) p < 0.0001 | 30 (48) p < 0.0001 |
EASI-75, n (%) | 7 (8) | 32 (38) p < 0.0001 | 34 (41) p < 0.0001 | 5 (6) | 17 (25) p = 0.0013 | 14 (23) p = 0.0047 |
EASI ≤ 7 at week 16, n (%) | 7 (8) | 28 (33) p < 0.0001 | 34 (41) p < 0.0001 | 5 (6) | 13 (19) p = 0.0049 | 14 (23) p = 0.0034 |
SCORAD total score LS mean change from baseline (SE) | − 13.2 (2.5) | − 33.2 (2.2) p < 0.0001 | − 35.8 (2.2) p < 0.0001 | − 12.4 (2.4) | − 29.0 (2.3) p < 0.0001 | − 29.9 (2.4) p < 0.0001 |
SCORAD total score LS mean percent change from baseline (SE) | − 17.6 (3.8) | − 47.5 (3.2) p < 0.0001 | − 51.6 (3.2) p < 0.0001 | − 15.8 (3.5) | −39.4 (3.4) p < 0.0001 | − 41.3 (3.5) p < 0.0001 |
BSA LS mean change from baseline (SE) | − 11.7 (2.7) | −33.4 (2.3) p < 0.0001 | − 30.1 (2.3) p < 0.0001 | − 10.8 (2.7) | − 31.3 (2.7) p < 0.0001 | − 24.5 (2.8) p = 0.0002 |
Peak Pruritus NRS score LS mean change from baseline (SE) | − 1.5 (0.3) | − 3.4 (0.3) p < 0.0001 | − 3.7 (0.3) p < 0.0001 | − 1.5 (0.3) | − 3.2 (0.3) p < 0.0001 | − 3.5 (0.3) p < 0.0001 |
Peak Pruritus NRS score LS mean percent change from baseline (SE) | − 19.0 (4.1) | − 45.5 (3.5) p < 0.0001 | − 47.9 (3.4) p < 0.0001 | − 17.4 (4.2) | − 41.2 (4.1) p < 0.0001 | − 44.2 (4.0) p < 0.0001 |
Peak Pruritus NRS ≥ 3-point improvement from baseline, n/N (%) | 8/85 (9) | 32/83 (39) p < 0.0001 | 40/82 (49) p < 0.0001 | 6/83 (7.2) | 21/69 (30.4) p = 0.0001 | 27/62 (43.5) p < 0.0001 |
Peak Pruritus NRS ≥ 4-point improvement from baseline, n/N (%) | 4/84 (5) | 22/83 (27) p = 0.0001 | 30/82 (37) p < 0.0001 | 3/82 (4) | 13/69 (19) p = 0.0025 | 21/62 (34) p < 0.0001 |
SCORAD—Pruritus VAS score LS mean change from baseline (SE) | − 2.1 (0.4) | − 4.0 (0.3) p = 0.0002 | − 4.4 (0.3) p < 0.0001 | − 2.0 (0.4) | − 3.4 (0.4) p = 0.0124 | − 3.8 (0.4) p = 0.0012 |
SCORAD—Sleep VAS score LS mean change from baseline (SE) | − 1.1 (0.4) | − 3.0 (0.3) p = 0.0001 | − 3.6 (0.3) p < 0.0001 | − 1.2 (0.4) | − 2.7 (0.4) p = 0.0071 | − 3.4 (0.4) p < 0.0001 |
POEM score LS mean change from baseline (SE) | − 3.8 (1.0) | − 9.5 (0.9) p < 0.0001 | − 10.1 (0.8) p < 0.0001 | − 3.5 (1.0) | − 8.4 (1.0) p = 0.0005 | − 8.5 (0.9) p = 0.0001 |
POEM ≥ 6-point improvement from baseline, n/N (%) | 8/84 (10) | 39/84 (46) p < 0.0001 | 52/82 (63) p < 0.0001 | 7/82 (9) | 27/69 (39) p < 0.0001 | 33/62 (53) p < 0.0001 |
CDLQI LS mean change from baseline (SE) | − 5.1 (0.6) | − 8.8 (0.5) p < 0.0001 | − 8.5 (0.5) p < 0.0001 | − 5.6 (0.7) | − 8.5 (0.6) p = 0.0022 | − 8.4 (0.6) p = 0.0023 |
CDLQI ≥ 6-point improvement from baseline, n/N (%) | 15/76 (20) | 42/71 (59) p < 0.0001 | 43/71 (61) p < 0.0001 | 14/74 (19) | 30/59 (51) p = 0.0002 | 32/56 (57) p < 0.0001 |
CDLQI ≤ 6 at week 16, n/N (%) | 13/73 (18) | 32/69 (46) p = 0.0003 | 36/69 (52) p < 0.0001 | 12/71 (17) | 21/57 (37) p = 0.0104 | 25/56 (45) p = 0.0007 |
HADS total score LS mean change from baseline (SE) | − 2.5 (0.8) | − 5.2 (0.7) p = 0.0133 | − 3.8 (0.7) p = 0.2203 | − 2.3 (0.8) | − 4.2 (0.8) p = 0.0939 | − 3.7 (0.8) p = 0.2076 |
HADS-A score LS mean change from baseline (SE) | − 1.6 (0.5) | − 2.7 (0.5) p = 0.1229 | − 2.3 (0.4) p = 0.2980 | − 1.5 (0.5) | − 1.9 (0.5) p = 0.5757 | − 2.2 (0.5) p = 0.3043 |
HADS-D score LS mean change from baseline (SE) | − 0.8 (0.4) | − 2.4 (0.4) p = 0.0016 | − 1.4 (0.3) p = 0.1691 | − 0.7 (0.4) | − 2.2 (0.4) p = 0.0076 | − 1.4 (0.4) p = 0.1892 |
PGADS “no” or “mild” symptoms, n (%) | 11 (13) | 33 (39) p < 0.0001 | 42 (51) p < 0.0001 | 10 (12) | 19 (28) p = 0.0149 | 26 (42) p < 0.0001 |
PGADS “moderate” symptoms, n (%) | 9 (11) | 15 (18) p = 0.1703 | 19 (23) p = 0.0304 | 8 (10) | 14 (20) | 15 (24) |
PGADS “severe” symptoms, n (%) | 10 (12) | 6 (7) p = 0.3007 | 6 (7) p = 0.3070 | 10 (12) | 6 (9) | 6 (10) |
PGADS “very severe” symptoms, n (%) | 55 (65) | 30 (36) | 15 (18) | 55 (66) | 30 (43) | 15 (24) |
Use of ≥ 1 rescue medication, n (%) | 50 (59) | 27 (32) | 17 (21) | 50 (60) | 27 (39) | 17 (27) |
Use of ≥ 1 systemic rescue medication, n (%) | 8 (9) | 0 | 1 (1) | 8 (10) | 0 | 2 (3) |