Dupilumab in Adolescents With Uncontrolled Moderate-To-Severe Atopic Dermatitis: Results From a Phase 2a and Subsequent Open-Label Extension Trial

Michael J. Cork, Diamant Thaci, Lawrence Eichenfield, Peter Arkwright, Thomas Hultsch, John D. Davis, Yi Zhang, Qin Zhang, Zhen Chen, Meng Li, Marius Ardeleanu, Ariel Teper, Bolanle Akinlade, Abhijit Gadkari, Laurent Eckert, Mohammed Kamal, Marcella Ruddy, Neil M. H. Graham, Gianluca Pirozzi, Neil StahlA. Thomas DiCioccio, Ashish Bansal

Research output: Contribution to journalArticlepeer-review

Abstract

IMPORTANCE: Dupilumab (monoclonal antibody inhibiting IL-4 and IL-13) is approved for adults with inadequately controlled moderate-to-severe atopic dermatitis (AD). Data from a 16-week, randomized, placebo-controlled Phase 3 trial in adolescents (NCT03054428) demonstrated significant improvements in AD signs and symptoms.OBJECTIVE: To characterize the pharmacokinetics and long-term safety and efficacy of dupilumab in adolescents.DESIGN: A Phase 2a, open-label, ascending-dose, sequential cohort study followed by a Phase 3, open-label extension.SETTING: Global, multicenter trials.PARTICIPANTS: Adolescents (aged ≥12 to <18 years) with moderate-to-severe AD.INTERVENTIONS: In the Phase 2a study, patients received a single dose of dupilumab (2-mg/kg or 4-mg/kg) followed by 8 weeks of pharmacokinetic sampling. Thereafter, these patients continued the same treatment regimen for four additional weekly doses, with 8-week safety follow-up. These patients were then enrolled into the open-label extension and continued on either dupilumab 2-mg/kg or 4-mg/kg weekly.MAIN OUTCOMES AND MEASURES: Primary endpoints of the Phase 2a and extension studies were the dupilumab concentration–time profile and incidence of treatment-emergent adverse events (TEAEs). Secondary outcomes included Eczema Area and Severity Index (EASI), Investigator’s Global Assessment, and peak pruritus Numerical Rating Scale.RESULTS: Forty adolescents received dupilumab in the Phase 2a study, and 36 continued in the open-label extension. Dupilumab showed non-linear, target-mediated pharmacokinetics. Dupilumab was well tolerated over a period of 52 weeks. The most frequent TEAEs were nasopharyngitis and AD exacerbation. After a single initial dose of dupilumab in the Phase 2a study, EASI improved from baseline to Week 2 (mean [±SD] reduction −34% [±20%] with 2-mg/kg and −51% [±29%] with 4-mg/kg). With continuing treatment in the Phase 2a and open-label extension, further improvements in EASI were seen at Week 52 (mean reduction −85% [±12%] with 2-mg/kg and −84% [±20%] with 4-mg/kg). Sustained improvements were also seen for all other predefined efficacy endpoints.CONCLUSIONS AND RELEVANCE: In adolescents with moderate-to-severe AD, dupilumab exhibited a pharmacokinetic profile similar to adults. Long-term safety and efficacy data further support the use of dupilumab in this population, extending and reinforcing the findings from the 16-week Phase 3 trial in adolescents.
Original languageEnglish
JournalBritish Journal of Dermatology
Early online date8 Oct 2019
DOIs
Publication statusPublished - 2019

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