Dupilumab demonstrated favorable safety and sustained efficacy in adults with moderate-to-severe atopic dermatitis (AD) for up to 3 years. |
The safety data reported in this open-label study are consistent with previously reported controlled studies of up to 52 weeks. |
These safety and efficacy data support the long-term, continuous use of dupilumab in adults with moderate-to-severe AD. |
1 Introduction
2 Methods
2.1 Study Design, Patients, and Treatment
2.2 Ethics
2.3 Outcomes Assessed in This Analysis
2.4 Statistical Analysis
3 Results
3.1 Patients
Dupilumab 300 mg qw [N = 2677]a | ||
---|---|---|
OLE study completion status | ||
Completed up to 1 year | 2207 (82.4) | |
Completed up to 2 years | 1028 (38.4) | |
Completed up to 3 years | 347 (13.0) | |
Completed studyb | 1061 (39.6) | |
Patients ongoing | 291 (10.9) | |
Withdrawn from study | 1325 (49.5) | |
Study terminated by sponsor (regulatory approval/commercialization) | 807 (30.1) | |
Withdrawal by subjectc | 221 (8.3) | |
Adverse eventd | 109 (4.1) | |
Lost to follow-up | 64 (2.4) | |
Lack of efficacy | 57 (2.1) | |
Protocol deviation | 32 (1.2) | |
Pregnancy | 17 (0.6) | |
Physician decision | 14 (0.5) | |
Unknown | 4 (0.1) | |
Demographics at parent study baseline | ||
Age, years [mean (SD)] | 39.2 (13.4) | |
Male | 1611 (60.2) | |
Race | ||
White | 1936 (72.3) | |
Black or African American | 147 (5.5) | |
Asian | 541 (20.2) | |
Other | 33 (1.2) | |
Not reported | 20 (0.7) | |
Height, cm [mean (SD)] | 170.7 (9.88) | |
Weight, kg [mean (SD)] | 77.1 (18.4) | |
BMI, kg/m2 [mean (SD)] | 26.4 (5.59) | |
Treatment in the parent study | ||
Previously treated with dupilumab | 1679 (62.7) | |
Dupilumab 300 mg qw | 807 (30.1) | |
Dupilumab 300 mg q2w | 536 (20.0) | |
Other dupilumab dosese | 336 (12.6) | |
Received placebo qw in the parent study | 968 (36.2) | |
Screen failuref | 30 (1.1) | |
Patients with concurrent atopic/allergic disease history at parent study baseline | 2627 (98.1) | |
Allergies (other) | 1749 (65.3) | |
Allergic rhinitis | 1332 (49.8) | |
Asthma | 1105 (41.3) | |
Food allergy | 1010 (37.7) | |
Allergic conjunctivitis | 740 (27.6) | |
Hives | 368 (13.7) | |
Chronic rhinosinusitis | 173 (6.5) | |
Atopic keratoconjunctivitis | 78 (2.9) | |
Nasal polyps | 63 (2.4) | |
Eosinophilic esophagitis | 13 (0.5) | |
Concomitant topical treatments for AD during the study | ||
Patients who used TCSs | 1416 (52.9) | |
Patients who used TCIs | 431 (16.1) | |
Patients who used TCSs or TCIs | 1487 (55.5) | |
Patients who used TCSs and TCIs | 360 (13.4) | |
Disease characteristics | Current study (OLE) | Parent study |
Duration of AD, years [mean (SD)] | 29.9 (14.8) | 29.0 (14.8) |
EASI (0–72) [mean (SD)] | 16.4 (14.6) | 32.8 (13.2) |
Patients with IGA score 0–4 [mean (SD)] | 2.7 (0.95) | 3.49 (0.50) |
0 or 1 | 320 (12.0) | 0 |
2 | 610 (22.8) | 0 |
3 | 1288 (48.1) | 1343 (50.2) |
4 | 459 (17.1) | 1301 (48.6) |
Missing | 0 | 30 (1.1) |
Patients with weekly average Pruritus NRS score (0–10) [mean (SD)] | 5.0 (2.45) | 7.1 (1.93) |
≥ 3 | 1769 (66.1) | 2528 (94.4) |
≥ 4 | 1505 (56.2) | 2437 (91.0) |
POEM total score (0–28) [mean (SD)] | 14.7 (8.00) | 20.5 (5.89) |
DLQI (0–30) [mean (SD)] | 8.5 (7.11) | 14.7 (7.38) |
3.2 Safety Assessment
Current study (OLE) | CHRONOS (52 weeks) | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
300 mg qw [N = 2677] | Placebo + TCS [n = 315] | 300 mg qw + TCS [n = 315] | ||||||||||
Events | Pts with ≥ 1 event, [n (%)] | nE/100 PY | nP/100 PY | Events | Pts with ≥ 1 event [n (%)] | nE/100 PY | nP/100 PY | Events | Pts with ≥ 1 event, [n (%)] | nE/100 PY | nP/100 PY | |
TEAEs | 13,826 | 2264 (84.6) | 270.1 | 173.7 | 1520 | 268 (85.1) | 531.9 | 325.1 | 1,500 | 263 (83.5) | 504.5 | 322.43 |
Serious TEAEs | 354 | 256 (9.6) | 6.92 | 5.28 | 24 | 16 (5.1) | 8.40 | 5.75 | 11 | 10 (3.2) | 3.70 | 3.40 |
Severe TEAEs | 355 | 246 (9.2) | 6.94 | 5.08 | 46 | 28 (8.9) | 16.10 | 10.31 | 24 | 17 (5.4) | 8.07 | 5.88 |
TEAEs leading to study drug discontinuation | 116 | 95 (3.5) | 2.27 | 1.87 | 29 | 25 (7.9) | 10.15 | 9.14 | 10 | 9 (2.9) | 3.36 | 3.06 |
Serious TEAEs related to treatment | 36 | 31 (1.2) | 0.70 | 0.61 | 3 | 3 (1.0) | 1.05 | 1.06 | 2 | 2 (0.6) | 0.67 | 0.68 |
Deatha | 2 | 2 (< 0.1) | 0.04 | 0.04 | 0 | 0 | 0 | 0 | 1 | 1 (0.3) | 0.34 | 0.34 |
Most common TEAEs by PT (≥ 5% of patients in the OLE) | ||||||||||||
Nasopharyngitis | 1543 | 752 (28.1) | 30.14 | 19.16 | 90 | 62 (19.7) | 31.49 | 24.93 | 86 | 62 (19.7) | 28.92 | 24.16 |
Atopic dermatitis | 736 | 438 (16.4) | 14.38 | 9.61 | 243 | 147 (46.7) | 85.03 | 74.32 | 91 | 55 (17.5) | 30.60 | 20.71 |
Upper respiratory tract infection | 532 | 350 (13.1) | 10.39 | 7.56 | 48 | 32 (10.2) | 16.80 | 12.03 | 65 | 43 (13.7) | 21.86 | 15.85 |
Headache | 408 | 216 (8.1) | 7.97 | 4.54 | 31 | 19 (6.0) | 10.85 | 6.98 | 48 | 25 (7.9) | 16.14 | 8.97 |
Conjunctivitisb | 826 | 521 (19.5) | 16.14 | 11.96 | 29 | 25 (7.9) | 10.15 | 9.24 | 91 | 61 (19.4) | 30.60 | 23.37 |
Injection-site reactions (HLT) | 855 | 260 (9.7) | 16.70 | 5.58 | 105 | 25 (7.9) | 36.74 | 9.39 | 232 | 63 (20.0) | 78.02 | 25.46 |
Herpes viral infections (HLT) | 715 | 333 (12.4) | 13.97 | 7.21 | 32 | 25 (7.9) | 11.20 | 9.17 | 43 | 22 (7.0) | 14.46 | 7.72 |
Skin infections | 291 | 231 (8.6) | 5.69 | 4.81 | NA | 57 (18.1) | NA | 20.21 | NA | 26 (8.3) | NA | 7.87 |
Eczema herpeticum (PT) | 14 | 12 (0.4) | 0.27 | 0.24 | 6 | 6 (1.9) | 2.10 | 2.13 | 0 | 0 | 0 | 0 |
Most common serious TEAEs by PT (≥ 0.2% of patients in the OLE) | ||||||||||||
Squamous cell carcinoma of skin | 14 | 8 (0.3) | 0.27 | 0.16 | 0 | 0 | 0 | 0 | 1 | 1 (0.3) | 0.34 | 0.34 |
Osteoarthritis | 10 | 9 (0.3) | 0.20 | 0.18 | 0 | 0 | 0 | 0 | 1 | 1 (0.3) | 0.34 | 0.34 |
Dermatitis atopic | 7 | 6 (0.2) | 0.14 | 0.12 | 1 | 1 (0.3) | 0.35 | 0.35 | 2 | 1 (0.3) | 0.67 | 0.34 |
Syncope | 6 | 5 (0.2) | 0.12 | 0.10 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Inguinal hernia | 5 | 5 (0.2) | 0.10 | 0.10 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Appendicitis | 5 | 5 (0.2) | 0.10 | 0.10 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
3.3 Efficacy
Dupilumab 300 mg qw [N = 2677] | |||
---|---|---|---|
Week 100 [n = 1028] | Week 124 [n = 529] | Week 148a [n = 347] | |
Patients achieving IGA 0 or 1 [n/N1 (%)] | 589/1014 (58.1) | 271/458 (59.2) | 43/58 (74.1) |
Patients achieving a reduction in IGA of ≥ 2 from baseline of the parent study [n/N1 (%)] | 769/996 (77.2) | 359/457 (78.6) | 58/66 (87.9) |
Patients achieving EASI-50 [n/N1 (%)] | 979/994 (98.5) | 445/453 (98.2) | 57/58 (98.3) |
Patients achieving EASI-75 [n/N1 (%)] | 908/994 (91.3) | 416/453 (91.8) | 56/58 (96.6) |
Patients achieving EASI-90 [n/N1 (%)] | 724/994 (72.8) | 337/453 (74.4) | 51/58 (87.9) |
EASI (primary analysis), observed values [mean (SD)] | 2.6 (3.6) | 2.3 (3.5) | 1.4 (3.2) |
OC (sensitivity analysis) [mean (SE)] | 2.6 (0.1) | 2.3 (0.2) | 1.5 (0.4) |
LOCF (sensitivity analysis) [mean (SE)] | 3.6 (0.2) | 3.6 (0.2) | 3.6 (0.2) |
MI (sensitivity analysis) [mean (SE)] | 2.9 (0.1) | 2.8 (0.1) | 3.5 (0.1) |
Change in EASI from baseline of the parent study, observed values [mean (SD)] | − 31.3 (14.1) | − 30.0 (13.6) | − 29.2 (14.2) |
LOCF (sensitivity analysis) [mean (SE)] | − 29.8 (0.4) | − 29.8 (0.4) | − 29.8 (0.4) |
MI (sensitivity analysis) [mean (SE)] | − 30.6 (0.4) | − 30.7 (0.4) | − 30.1 (0.4) |
Percentage change in EASI from baseline of the parent study, % [mean (SD)] | − 91.5 (12.6) | − 92.3 (11.0) | − 95.4 (9.3) |
Weekly Pruritus NRS (primary analysis), observed values [mean (SD)] | 2.3 (1.9) | 2.3 (1.8) | 2.2 (1.8) |
OC (sensitivity analysis), mean (SE) | 2.3 (0.1) | 2.3 (0.1) | 2.1 (0.1) |
LOCF (sensitivity analysis), mean (SE) | 2.5 (0.1) | 2.6 (0.1) | 2.6 (0.1) |
MI (sensitivity analysis), mean (SE) | 2.4 (0.1) | 2.6 (0.1) | 2.5 (0.1) |
Change in weekly Pruritus NRS from baseline of the parent study (primary analysis), observed values [mean (SD)] | − 4.7 (2.3) | − 4.5 (2.4) | − 4.4 (2.4) |
LOCF (sensitivity analysis) [mean (SE)] | − 4.7 (0.1) | − 4.6 (0.1) | − 4.6 (0.1) |
MI (sensitivity analysis) [mean (SE)] | − 4.8 (0.1) | − 4.6 (0.1) | − 4.7 (0.1) |
Percent change in weekly Pruritus NRS from baseline of the parent study, % [mean (SD)] | − 65.7 (30.2) | − 64.2 (33.4) | − 65.4 (28.5) |
Patients achieving ≥ 3 reduction in weekly Pruritus NRS from baseline of the parent study [n/N1 (%)] | 604/764 (79.1) | 313/416 (75.2) | 168/224 (75.0) |
Patients achieving weekly average Pruritus NRS ≤ 3 [n/N1 (%)] | 686/888 (77.3) | 395/510 (77.5) | 217/265 (81.9) |
POEM score [mean (SD)] | 5.4 (5.1) | 5.1 (5.3) | N/A |
DLQI [mean (SD)] | 2.9 (3.9) | 2.9 (4.3) | N/A |