Dupilumab in the Treatment of Adolescent Patients with Severe and Refractory Atopic Dermatitis
An open multicenter study evaluating dupilumab in the treatment of moderate to severe atopic dermatitis in adolescents confirmed its long-term efficacy and safety in this age group. In addition to its results, we also summarize information on dosing and reimbursement conditions in the Czech Republic for the age group 12-18 years.
Introduction
Dupilumab is a monoclonal antibody that inhibits the signaling pathway of interleukins 4 and 13. It is approved for the treatment of moderate to severe atopic dermatitis in adults and in adolescents aged 12-18 years who are candidates for systemic therapy.
In a previous 16-week multicenter randomized placebo-controlled study in adolescents, dupilumab showed significant reduction in the manifestations and symptoms of atopic dermatitis and an acceptable safety profile. The goal of the new study conducted in adolescents was to describe the pharmacokinetics and long-term efficacy and safety of dupilumab in this age group.
Study Course
In the first part of the phase IIa study, patients aged 12-18 years with moderate to severe atopic dermatitis received a single dose of 2 mg/kg or 4 mg/kg dupilumab. This was followed by an 8-week pharmacokinetic monitoring. Subsequently, patients received the same dose once weekly for 4 weeks, with safety monitored for 8 weeks. This study was followed by an open-label phase III extension study. Patients continued using dupilumab 2 or 4 mg/kg weekly and were monitored for a total of 52 weeks.
A total of 40 patients were enrolled, with 36 continuing in the open-label extension.
Results
The results showed a pharmacokinetic profile of dupilumab similar to that in adult patients.
Treatment was well tolerated throughout the 52-week period. The most common adverse events were nasopharyngitis and exacerbation of atopic dermatitis.
Two weeks after the first dose, the average reduction in the Eczema Area and Severity Index (EASI) was 34% in the 2 mg/kg group and 51% in the 4 mg/kg group. EASI scores continued to decrease, and by week 52, improvement was seen in 85% of the lower-dose group and 84% of the higher-dose group.
Dupilumab Dosing and Therapeutic Combinations
Dupilumab is administered subcutaneously to the abdomen, upper arm, or thigh. The dosing for adolescent patients is shown in the following table.
Table: Dupilumab Dosing in Adolescent Patients
|
Body Weight |
Initial Dose |
Subsequent Doses (once every 14 days) |
|
< 60 kg |
400 mg (2 injections of 200 mg each) |
200 mg |
|
≥ 60 kg |
600 mg (2 injections of 300 mg each) |
300 mg |
Dupilumab can be used with or without topical corticosteroids. Topical calcineurin inhibitors can also be used concurrently, but they should be reserved for problematic areas such as the face, neck, intertriginous regions, and genital areas.
Reimbursement Conditions and Assessment of Treatment Success
In the Czech Republic, dupilumab is reimbursed for adolescent patients (from 12 years to reaching 18 years) with severe atopic dermatitis who have not achieved disease control with maximized local therapy and available higher-level treatments such as phototherapy, balneotherapy, or systemic therapy.
Therapy success is evaluated at 16 and 24 weeks from the start of treatment and then at least every 24 weeks. Treatment is discontinued in case of failure to achieve at least EASI-50 at week 16, failure to achieve at least EASI-75 at week 24, occurrence of unmanageable side effects, insufficient adherence to therapy, or reduction in efficacy below EASI-50 at two consecutive follow-ups.
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Sources:
1. Cork M. J., Thaçi D., Eichenfield L. F. et al. Dupilumab in adolescents with uncontrolled moderate-to-severe atopic dermatitis: results from a phase IIa open-label trial and subsequent phase III open-label extension. Br J Dermatol 2020 Jan; 182 (1): 85−96, doi: 10.1111/bjd.18476.
2. SPC Dupixent. Available at: www.ema.europa.eu/en/documents/product-information/dupixent-epar-product-information_cs.pdf
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