Quick Relief from Severe AD Symptoms – Dupilumab for Children Aged 6 Years and Older
Children aged 6-12 with severe atopic dermatitis (AD) have very limited treatment options. The studies presented below demonstrate how effective and safe dupilumab, a monoclonal antibody targeting interleukins 4 and 13, is in their case. Since October, this medication is newly covered even for children from 6 years of age.
Atopic Dermatitis in Children
Atopic dermatitis is the most common inflammatory skin condition in children. Between the ages of 6 and 12, it occurs with a prevalence of up to 20%, with 8% of these children having severe AD. This condition significantly negatively impacts patients' quality of life (sleep deprivation, irritability, stress...) and heavily affects family members, including substantial financial burden.
The availability of medications that improve the course of severe disease and have a favorable benefit-to-risk ratio for children with AD is limited. Systemic corticosteroids are strongly discouraged; other systemic drugs are used in children off-label and offer an unacceptable benefit-to-risk ratio. Only a few controlled studies provide data to support the use of these drugs in children.
Treating AD with Dupilumab
Dupilumab is a fully human monoclonal antibody that blocks the shared receptor component for interleukins (IL) 4 and 13. By blocking the signaling pathways of both interleukins, the drug exerts an anti-inflammatory effect. In addition to AD, it is also indicated for the treatment of asthma and chronic rhinosinusitis with nasal polyposis.
Two Pediatric Studies
An open-label phase IIa study investigated the pharmacokinetic profile, safety, and efficacy of dupilumab. The study included children aged 6 to 12 years with severe AD that insufficiently responded to topical treatment and affected > 10% of body surface area. In the first part of the study, patients received 1 dose of dupilumab (2 or 4 mg/kg) subcutaneously and were followed for 8 weeks. In the second part, 2 or 4 mg/kg of dupilumab was administered subcutaneously once a week for 4 weeks. The 2 mg/kg dose was selected as the initial dose before advancing to the 4 mg/kg dose to assess the drug's safety.
The extended open-label continuation of the phase III LIBERTY AD PED-OLE study is still ongoing. Its goal is to evaluate the long-term safety and efficacy of the drug. The study includes children who previously participated in the previous dupilumab study. In this study, patients continue to take the same dose of the drug as in phase IIa (2 or 4 mg/kg). The results presented below are from patients who participated in both studies (data from the second study is a summary of the first 52 weeks of treatment).
Results
Of the 38 initially enrolled children, 37 completed the phase IIa study, and 33 continued into the phase III extension study. The average age of patients was 8 years, and the average duration of AD was 7 years.
Symptoms of atopic dermatitis, including pruritus, showed rapid improvement after a single dose of dupilumab in the phase IIa study. Improvement in clinical scores (EASI, SCORAD) and Peak Pruritus NRS was observed as early as the 2nd week of treatment, with further improvement during continued treatment up to the 52nd week in the second study. Long-term treatment also improved patients' quality of life.
Most adverse events in the phase IIa study were mild to moderate, with 14% of patients experiencing a severe adverse event. Serious adverse events included bacterial arthritis, impetiginized dermatitis, and exacerbation of AD. None of the adverse events led to discontinuation of treatment. More adverse events occurred in the group receiving the 4 mg/kg dose, which was due to a higher incidence of skin infections, cough, and impetiginized dermatitis. In the second study, the incidence of adverse events was comparable between the two doses. The most common adverse events in the phase III study were nasopharyngitis (2 mg/kg: 47%; 4 mg/kg: 56%) and exacerbation of AD (29% and 13% of children).
Conclusion
The safety and efficacy results from two consecutive clinical studies confirm the suitability of dupilumab for the long-term treatment of severe atopic dermatitis in children from 6 years of age.
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Source: Cork M. J., Thaçi D., Eichenfield L. F. et al. Dupilumab provides favourable long-term safety and efficacy in children aged ≥ 6 to < 12 years with uncontrolled severe atopic dermatitis: results from an open-label phase IIa study and subsequent phase III open-label extension study. Br J Dermatol 2021 May; 184 (5): 857−870, doi: 10.1111/bjd.19460.
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