
Dupilumab Efficacy in AD Not Affected by Age of Disease Onset
Dupilumab exhibited similarly significant and sustained improvements in atopic dermatitis (AD) signs, symptoms, and quality of life of adult patients with moderate to severe AD, regardless of age of disease onset, compared with placebo.
The efficacy of dupilumab among adult patients with moderate to severe
AD is a heterogeneous inflammotory skin condition that is associated with different genetics, lesion morphology and distribution, and symptoms by age of onset. Compared with adolescent patients, those with adult-onset AD show lower immunoglobulin E responses and a predilection for flexural sites, and they possibly have a greater frequency of associated morphologic variants, noted researchers.
“Little is known about possible differences in treatment efficacy between adults with adult-onset or childhood-onset AD,” they said.
Dupilumab, a fully human monoclonal antibody that blocks 2 key and central drivers of type 2 inflammation, interleukin (IL)-4 and IL-13, is
The researchers sought to explore whether possible endophenotypic differences linked to age of onset and differences in disease duration at baseline would affect the efficacy of dupilumab among adult patients with moderate to severe AD.
They conducted a post hoc analysis of pooled data from the LIBERTY AD
A total of 460 patients in the placebo group and 457 in the dupilumab 300-mg every-2 weeks-group were included in the analysis. Overall, the mean age of patients at baseline was 38 years, with a mean duration of AD of approximately 28 years. Most patients (53.2%) reported AD onset at 0 to 4 years, with 14% at 5 to 9 years, 13.4% at 10 to 19 years, and 18.5% at 20 years or older.
Findings showed that dupilumab significantly improved AD signs and symptoms over 16 weeks compared with placebo, regardless of age of onset:
- Dupilumab treatment resulted in a significantly greater proportion of patients achieving Eczema Area and Severity Index (EASI)-75 (75% improvement from baseline EASI) (LS mean range, 38%-54%) vs placebo (LS mean range, 10%-19%; P < .0001), irrespective of age of AD onset
- Dupilumab treatment resulted in a significantly greater proportion of patients achieving EASI-50 and EASI-90 (50% and 90% improvement from baseline EASI, respectively) in all age-of-onset subgroups vs placebo
- Clear or almost clear skin (Investigator’s Global Assessment score 0 or 1) was achieved in 25% to 42% of patients across the dupilumab age-of-onset subgroups vs 7% to 14% in the placebo groups (P < .05 for all comparisons)
Furthermore, EASI improvements were significant across all anatomical regions (head/neck, upper extremities, lower extremities, and trunk) in all subgroups. Patient-reported weekly average peak pruritus Numerical Rating Scale and Dermatology Life Quality Index also improved consistently and significantly with dupilumab vs placebo, regardless of age of onset.
The small sample sizes of the age-of-onset subgroups were noted as a potential limitation of the study findings, as was the self-reported age of AD onset metrics, which the researchers said could lead to incorrect categorization of age of onset.
They concluded that these findings support targeting both IL-4 and IL-13 as an effective treatment strategy for AD across all ages of onset.
Reference
Silverberg JI, Boguniewicz M, Hanifin J, et al. Dupilumab treatment in adults with moderate-to-severe atopic dermatitis is efficacious regardless of age of disease onset: a post hoc analysis of two phase 3 clinical trials. Dermatol Ther (Heidelb). Published online October 21, 2022. doi:10.1007/s13555-022-00822-x
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