For adolescent patients with uncontrolled atopic dermatitis (AD), short-term dupilumab treatment is efficacious with an acceptable safety profile. However, long-term safety and efficacy data for the approved dose regimen of dupilumab in adolescents with AD are limited. |
In this long-term open-label extension study, dupilumab treatment every 4 weeks, or uptitrated to a weight-tiered dose regimen every 2 weeks, for up to 52 weeks showed an acceptable safety profile and provided sustained and substantial clinical benefits in AD signs and symptoms as well as improvements in quality of life. |
Most patients required uptitration of dupilumab dosing during the study from every 4 weeks to the approved dose regimen in adolescent patients of every 2 weeks. The results also support continued use of dupilumab to maintain efficacy, since most responding patients who stopped medication experienced disease recurrence. |
1 Introduction
2 Methods
2.1 Study Design
2.2 Main Inclusion and Exclusion Criteria
2.3 Treatment
2.4 Outcomes
2.5 Analyses
2.6 Compliance with Ethical Standards
3 Results
3.1 Patient Baseline Demographics and Clinical Characteristics
Characteristic | All patients (N = 294) |
---|---|
Age, years | 14.7 ± 1.7 |
Sex, male | 167 (56.8) |
Race | |
White | 203 (69.0) |
Black or African American | 30 (10.2) |
Asian | 42 (14.3) |
American Indian or Alaska Native | 2 (0.7) |
Native Hawaiian or other Pacific Islander | 5 (1.7) |
Other | 8 (2.7) |
Not reported | 4 (1.4) |
Ethnicity | |
Not Hispanic or Latino | 242 (82.3) |
Hispanic or Latino | 52 (17.7) |
Weight, kg | 64.8 ± 20.2 |
Weight group, kg | |
< 60 | 146 (49.7) |
≥ 60 | 148 (50.3) |
BMI, kg/m2 | 24.1 ± 6.0 |
BMI ≥ 85th percentile of population | 121 (41.2) |
Duration of AD, years | 12.5 ± 3.2 |
IGA | |
0 | 4 (1.4) |
1 | 23 (7.8) |
2 | 55 (18.7) |
3 | 139 (47.3) |
4 | 73 (24.8) |
EASI | 19.9 ± 15.6 |
BSA affected by AD | 34.1 ± 25.3 |
SCORAD | 46.7 ± 21.3 |
CDLQI | 7.0 ± 6.1 |
Patients with ongoing or history of allergic/atopic conditions | 294 (100) |
Allergic rhinitis | 185 (62.9) |
Food allergy | 171 (58.2) |
Asthma | 147 (50.0) |
Hives | 72 (24.5) |
Allergic conjunctivitis | 65 (22.1) |
Chronic rhinosinusitis | 16 (5.4) |
Nasal polyps | 5 (1.7) |
Aspirin sensitivity | 4 (1.4) |
Eosinophilic esophagitis | 1 (0.3) |
Other allergies | 200 (68.0) |
Patients receiving prior systemic medications for AD | 182 (61.9) |
Patients receiving prior systemic corticosteroids | 124 (42.2) |
Patients receiving prior systemic nonsteroidal immunosuppressants | 138 (46.9) |
Cyclosporine | 71 (24.1) |
Methotrexate | 43 (14.6) |
Mycophenolate mofetil | 10 (3.4) |
Azathioprine | 7 (2.4) |
3.2 Safety Assessment
TEAEs | All patients (N = 294) | |
---|---|---|
nE | nE/100PY | |
Total number of TEAEs | 1131 | 370.2 |
Total number of serious TEAEs | 5 | 1.6 |
Total number of severe TEAEs | 12 | 3.9 |
Total number of TEAEs related to treatment | 120 | 39.3 |
Total number of TEAEs related to permanent treatment discontinuation | 2 | 0.7 |
n (%) | nP/100PY | |
---|---|---|
Patients with any TEAE | 217 (73.8) | 194.6 |
Patients with any serious TEAE | 5 (1.7) | 1.7 |
Patients with any severe TEAE | 11 (3.7) | 3.8 |
Patients with any TEAEs related to treatment | 53 (18.0) | 20.2 |
Patients with any TEAEs leading to permanent discontinuation | 2 (0.7) | 0.7 |
Conjunctivitis clustera | 26 (8.8) | 9.2 |
Injection-site reactions (HLT) | 19 (6.5) | 6.6 |
Skin infections and infestations (SOC)b | 37 (12.6) | 13.9 |
Most common TEAEs reported in ≥3% of patients (PT) | ||
Nasopharyngitis | 60 (20.4) | 23.6 |
Dermatitis atopic | 56 (19.0) | 21.3 |
Upper respiratory tract infection | 35 (11.9) | 12.5 |
Headache | 26 (8.8) | 9.3 |
Oropharyngeal pain | 16 (5.4) | 5.6 |
Vomiting | 13 (4.4) | 4.5 |
Influenza | 13 (4.4) | 4.4 |
Oral herpes | 12 (4.1) | 4.2 |
Conjunctivitis | 12 (4.1) | 4.1 |
Pyrexia | 12 (4.1) | 4.1 |
Acne | 11 (3.7) | 3.8 |
Conjunctivitis allergic | 11 (3.7) | 3.7 |
Diarrhea | 10 (3.4) | 3.5 |
Abdominal pain upper | 10 (3.4) | 3.4 |
Cough | 9 (3.1) | 3.1 |
Sinusitis | 9 (3.1) | 3.0 |
Viral upper respiratory tract infection | 9 (3.1) | 3.0 |
3.3 Efficacy Outcomes
Efficacy assessment | All patients (N = 294) |
---|---|
Proportion of patients achieving IGA 0/1 | 44/103 (42.7) |
Proportion of patients achieving EASI-50 | 94/101 (93.1) |
Proportion of patients achieving EASI-75 | 82/101 (81.2) |
Proportion of patients achieving EASI-90 | 57/101 (56.4) |
Percentage change from baseline of parent study in EASI | − 83.5 ± 23.5 |
Change from baseline of parent study in EASI | − 28.5 ± 14.9 |
Change from baseline of parent study in % BSA affected by AD | − 42.7 ± 26.2 |
Percentage change from baseline of parent study SCORAD | − 65.0 ± 21.3 |
Change from baseline of parent study in CDLQI | − 11.8 ± 6.7 |
Patients with uptitration | All patients (N = 294) |
---|---|
Number of patients who received at least one q4w dose | 293a |
Number of patients who received q4w dose for at least 16 weeks | 289 |
Number of patients with uptitration | 205/289 (70.9) |
Number of patients with uptitration prior to week 16 | 105/289 (36.3) |
Number of patients with uptitration at or after week 16 | 100/289 (34.6) |
Time in weeks from start of q4w dose to first uptitration visit | 12.5 ± 9.8 |
Median (Q1–Q3) | 12.0 (4.0–16.0) |
Minimum; maximum | 2.0; 52.0 |
Patients | All patients (N = 294) |
---|---|
Proportion of patients with IGA 0/1 sustained over 12 weeks at week 52, n/N1 (%) | 30/102 (29.4) |
Patients who re-initiated treatment after relapse, n/N2 (%) | 17/30 (56.7) |
Time in weeks to study drug re-initiation following relapse | 17.5 ± 17.3 |
Minimum; maximum | 2.0; 64.0 |
Patients regaining IGA 0/1 following re-initiation, n/N3 (%) | 10/11 (90.9) |
Time in weeks to achievement of IGA 0/1 following re-initiation, mean ± SD | 20.7 ± 18.9 |
Minimum; maximum | 3.7; 64.0 |