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

Research output: Contribution to journalArticle

  • External authors:
  • Michael J. Cork
  • Diamant Thaci
  • Lawrence Eichenfield
  • 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 Stahl
  • A. Thomas DiCioccio
  • Ashish Bansal

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.

Bibliographical metadata

Original languageEnglish
JournalBritish Journal of Dermatology
Early online date8 Oct 2019
DOIs
Publication statusPublished - 2019