Lebrikizumab phase 3 data show improvements in atopic dermatitis symptoms, itch in children

Phase 3 results from the ADorable-1 study showed improvements in skin clearance, itch, and quality of life among children and adolescents with moderate-to-severe atopic dermatitis treated with lebrikizumab plus topical corticosteroids, according to recently presented data at the Society for Pediatric Dermatology Annual Meeting. The study included patients aged 6 months through 17 years, providing data across a broad pediatric age range, including infants and young children.

In this Q&A, Lawrence Eichenfield, MD, distinguished professor of dermatology and pediatrics and vice chair of the Department of Dermatology at the University of California San Diego School of Medicine, and chief of pediatric and adolescent dermatology at Rady Children’s Hospital San Diego, discusses the clinical significance of the ADorable-1 findings. Eichenfield highlights improvements in disease severity and itch, the broader effects of treatment on children’s quality of life and sleep, and the safety findings pediatricians should consider when discussing treatment options with families.

Contemporary Pediatrics: What stood out to you most from these Phase 3 results in children and adolescents with moderate-to-severe atopic dermatitis?

Lawrence Eichenfield, MD: Atopic dermatitis is an incredibly common condition in childhood, and there is only one biologic option approved down to 6 months of age, the IL-4/IL-13 blocker Dupilumab [(Dupixent; Sanofi and Regeneron)]. The Adorable-1 study of lebrikizumab, an IL-13 blocker, showed rapid response and excellent results in children 6 months of age through 17 years of age through 16 weeks of treatment, with almost 40% of patients having 90% improvement in eczema extent and severity. Improvement in itching was also seen, as well as in the quality of life of affected children.

Contemporary Pediatrics: Itch can have a significant impact on children with atopic dermatitis. What did the study show about improvements in itch, and why is this an important treatment outcome for pediatric patients?

Eichenfield: The study showed significantly decreased itching in children treated with lebrikizumab/topical steroid; the 6-year-olds and older had the ‘worse itch in 24 hours’ score measured, and 34.5% had at least a 4-point drop in itch from a baseline average of 6.4 out of 10 (vs. 5.5% of the placebo/topical steroid group with a similar baseline). The under 6-year-olds were assessed with the “worse scratching/itch score,” which relies on caregiver assessment (as you can’t ask younger children “What was your worst itch in the last 24 hours with a 0-10 score?”, and 41.6% had a 4-point drop vs none in the placebo/topical steroid group. Itch is of tremendous importance in pediatric AD, especially as it impacts the patient (and family’s) sleep!

Contemporary Pediatrics: The study reported improvements in skin clearance and overall disease severity. How clinically meaningful were these results, particularly for children with more severe disease?

Eichenfield: The endpoints used in the study measure the patient being clear or almost clear after 16 weeks of treatment, and in this study comparing lebrikizumab with topical steroids vs placebo with topical steroids. The 43.5% making this outcome at 16 weeks vs 15.2% with the placebo and topical steroid is both statistically significant and medically meaningful, especially as our experience would make us think that longer treatments beyond 16 weeks would allow even a higher percentage of children to reach this important endpoint. Another measure assessed was the EASI 75, which measures a 75% or greater improvement in the eczema area and severity index compared to baseline. Almost 63% of the children made the EASI 75 threshold, as compared to 21.6% with the placebo (and topical steroids).

Contemporary Pediatrics: Beyond skin symptoms, what did the findings show about quality of life, and how should pediatricians consider these broader effects when evaluating treatment response?

Eichenfield: Atopic dermatitis doesn’t just cause rashes and itch, with studies showing tremendous impact on the life of affected children with AD. The Children’s Dermatology Life Quality Index measures the impact of the disease on symptoms and feelings, school/holiday and leisure activities, personal relationships, sleep, and burdens of treatment. Quality-of-life scores improved impressively in this study. Pediatricians should appreciate that effective control of more severe disease can be life-changing to the child and the family.

Contemporary Pediatrics: What should pediatricians know about the safety findings from this study, and how might these data inform conversations with families about treatment options for moderate-to-severe atopic dermatitis?

Eichenfield: We are pleased that lebrikizumab in this pediatric trial showed excellent safety consistent with what has been seen in adolescents and adults. This cytokine blocker is not an immunosuppressive, and the side effect profile showed few serious adverse events, with no discontinuation of the study due to adverse events. We expect that, like in our older patients using this drug, no baseline blood work or monitoring blood work would be needed.