Lebrikizumab helps clear skin of teens with moderate-to-severe atopic dermatitis

Treatment with lebrikizumab with or without topical corticosteroids (TCS) results in clinical improvement among adolescents with moderate-to-severe atopic dermatitis (AD), according to a study presented at the recent AAD 2023.

Lead researcher Adelaide Hebert, chief of paediatric dermatology at McGovern School of Medicine and Children’s Memorial Hermann Hospital in Texas, US, and her team assessed the efficacy outcomes of lebrikizumab at 16 weeks in adolescent patients with moderate-to-severe AD from three randomized, double-blind, placebo-controlled phase III trials: ADvocate 1, ADvocate 2, and ADhere.

Adolescent participants (aged 12 to 18 years, weighing ≥40 kg) were randomly assigned to receive subcutaneous lebrikizumab (loading doses of 500 mg at baseline and week 2, followed by 250 mg every 2 weeks) or placebo in ADvocate 1 and 2 as monotherapy, and in combination with TCS in ADhere.

At week 16, efficacy was assessed using IGA (0,1) with ≥2-point improvement, EASI-75, and Pruritus NRS ≥4-point improvement. Hermann and colleagues pooled adolescent data from ADvocate 1 and 2 and analysed ADhere data separately. They conducted ADvocate 2 and ADhere analyses on a modified population, excluding 10 adolescents from a single site whose eligibility could not be confirmed.

Pooled 16-week adolescent data from ADvocate 1 and 2 (lebrikizumab [n=67] vs placebo [n=35]) were as follows: IGA (0,1) with ≥2-point improvement from baseline, 46.6 percent vs 14.3 percent (p<0.01); EASI-75, 62.0 percent vs 17.3 percent (p<0.001), and Pruritis NRS ≥4-point improvement from baseline, 48.9 percent vs 13.1 percent (p<0.01), respectively. [AAD 2023, abstract 43072]

In ADhere (lebrikizumab + TCS [n=32] vs placebo + TCS [n=14]), the corresponding results were as follows: IGA (0,1), 57.3 percent vs 28.6 percent (p=0.071); EASI-75, 88.0 percent vs 57.1 percent (p<0.05); and Pruritus NRS, 45.8 percent vs 13.8 percent (p=0.078).

Phase III trials

“Lebrikizumab, a high-affinity monoclonal antibody targeting interleukin (IL)-13, previously demonstrated clinical efficacy in adults and adolescents with AD in phase III trials,” said the researchers.

Specifically, 43 percent of patients in ADvocate 1 who had received lebrikizumab achieved clear or almost clear skin at 16 weeks relative to just 13 percent of those treated with placebo. Among patients treated with lebrikizumab, 59 percent achieved an EASI-75 response compared to 16 percent with placebo. [https://bit.ly/3UFnwDD]

In ADvocate 2, 33 percent of lebrikizumab recipients achieved clear or almost clear skin at 16 weeks compared to only 11 percent of those on placebo. Among lebrikizumab-treated patients, 51 percent achieved an EASI-75 response relative to 18 percent of those on placebo. [https://bit.ly/3UFnwDD]

In ADhere, the combination of lebrikizumab and TCS correlated with improved outcomes in adolescents and adults with moderate-to severe AD compared with TCS alone. In addition, safety was consistent with that in previous AD trials. [JAMA Dermatol 2023;159:182-191]

Lebrikizumab binds to the IL-13 protein to prevent the formation of IL-13Rα1/IL-4Rα (type 2 receptor), which blocks downstream signaling through the IL-13 pathway. [Exp Dermatol 2019;28:756-768; J Mol Biol 2013;425:1330-1339; Pulm Pharmacol Ther 2017;46:88-98]

IL-13 is responsible for the signs and symptoms in AD, such as skin barrier dysfunction, itch, infection, and hard, thickened areas of skin. [Allergy 2020;75:54-62]