Data from the LIBERTY AD PRESCHOOL trial, and its ongoing open-label extension analysis show that dupilumab is safe and clinically effective, and can lead to statistically significant symptom improvement among patients aged 6 months to 17 years who have moderate to severe atopic dermatitis (AD).
Short- and long-term data on treatment for moderate to severe atopic dermatitis (AD) among patients aged 6 months to younger than 18 years show that treatment with dupilumab is well tolerated, safe, and can lead to statistically significant symptom improvement.
Investigators presented their findings from the LIBERTY AD PRESCHOOL trial1 and its ongoing open-label extension (OLE) analysis2 at the recent annual meeting of the American Academy of Dermatology, which took place in New Orleans.
In the LIBERTY AD PRESCHOOL trial,1 significant improvement in signs of AD was indicated by a score of 0 or 1 on the Investigator’s Global Assessment Scale (IGA; scored from 0 [clear] to 4 [severe AD]), indicating clear or almost clear skin. Higher scores on the IGA indicate greater disease severity. There were 72 patients in the placebo group (placebo plus low-potency topical corticosteroids [TCS]) and 58 in the dupilumab group (treatment every 4 weeks; 200 mg for a baseline weight of ≥ 5 to < 15 kg and 300 mg for a baseline weight of ≥ 15 to < 30 kg plus low-potency TCS). The study investigators were aiming to report how the signs and symptoms of AD changed in their pediatric patient population for those with an IGA score above 1 after 16 weeks of treatment.
Mean (SD) patient ages were equivalent, at 3.4 (2.1) years in the placebo group and 3.8 (1.3) years in the dupilumab group for those with an IGA score of 0/1 at week 16, and 3.8 (1.2) and 4.0 (1.2) years, respectively, for those with an IGA score above 1 at week 16. The mean weights ranged from 15.6 (6.1) to 17.2 (5.7) kg. The Eczema Area and Severity Index (EASI), Worst Pruritus Numerical Rating Scale (NRS), and Patient-Oriented Eczema Measure (POEM) all factored into symptom evaluation.
Compared with baseline, patients in the dupilumab group who did not achieve an IGA of 0/1 still had a greater change in AD symptom improvement at week 16 vs the placebo group in EASI and Worst Pruritus-NRS, and more achieved at least a 6-point reduction in POEM:
More caregivers of the patients in the treatment group (72.4%) also noted symptoms were “much better/moderately better” compared with the placebo group (25.0%).
In addition, among the patients who had an IGA score of 0/1 at week 16, 25 saw almost complete improvement according to EASI, 23 saw a more than 60% improvement in Worst Pruritus-NRS, and 88% had a least a 6-point POEM reduction. Ninety-two percent of these caregivers reported symptoms were “much better/moderately better.”
The researchers concluded that their patients who did not achieve an IGA score of 0/1 still saw significant improvement in their overall AD symptoms. They also note that use of that score could “significantly underestimate clinically relevant dupilumab-induced treatment effects.
In the OLE analysis,2 patients were included if they completed LIBERTY AD PRESCHOOL, with safety data reported through July 31, 2021. Treatment consisted of the following:
Among the 180-patient cohort at baseline, the mean age was 3.86 (1.322) years and most were of White (66.1%) or Black/African American (18.9%) ethnicity and male (64.4%). Most completed treatment up to 16 weeks (67.8%), followed by 24 weeks (41.4%), 26 weeks (37.8%), 52 weeks (16.7%), 78 weeks (16.7%), 104 weeks (16.1%), and 156 weeks (8.3%). Ninety-three percent are still enrolled.
Comparing outcomes between the parent and OLE studies, more patients in the OLE placebo group (n = 78) reported any treatment-emergent adverse event (TEAE) compared with overall in LIBERTY AD PRESCHOOL and the OLE treatment group (n = 83): 74.4% vs 60.6% vs 63.9%. The corresponding rates of drug-related TEAEs were 6.4%, 8.3%, and 10.8%. Four patients in the OLE placebo group reported a serious TEAE compared with 2 in the parent study and none in the OLE dupilumab group. Only 1 patient from each group reported a TEAE leading to drug discontinuation, and there were no treatment-related deaths.
Per 100 patient-years, the most common AEs reported were nasopharyngitis, pyrexia, and upper respiratory tract infection in 21.09, 18.91, and 18.02 in the parent analysis; AD, nasopharyngitis, and pyrexia in 129.69, 29.99, and 29.96 in the OLE placebo group; and AD, nasopharyngitis, and upper respiratory tract infection in 49.69, 27.67, and 19.49 in the OLE treatment group.
The researchers of the OLE analysis concluded that long-term treatment with dupilumab—up to 156 weeks is generally well tolerated and safe to use among pediatric patients.
1. Paller AS, Siegfried EC, Lockshin B, Praestgaard A, Shumel B, Prescilla R. Clinically important benefits in infants and young children with moderate-to-severe atopic dermatitis not achieving IGA 0/1 after 16 weeks of dupilumab treatment. Presented at: AAD 2023; March 17-21, 2023; New Orleans, LA. https://bit.ly/3TtGNaa
2. Paller AS, Siegfried EC, Sidbury R, et al. Treatment-emergent adverse events in patients aged 6 months to 5 years with moderate-to-severe atopic dermatitis treated with dupilumab in an open-label extension clinical trial. Presented at: AAD 2023; March 17-21, 2023; New Orleans, LA. https://bit.ly/3ZhG4KR