A Phase IIb dose-ranging efficacy and safety study of tralokinumab in adult patients with moderate-to-severe atopic dermatitis (AD)
Presenters: Wollenberg A1, Howell MD2, Guttman-Yassky E3, Silverberg JI4, Birrell C5, Kell C5, Ranade K2, Dawson M5, van der Merwe R5
Affiliations: 1Ludwig Maximillian University, Munich, Germany; 2MedImmune, LLC, MD; 3Mount Sinai School of Medicine, NY; 4Northwestern University Feinberg School of Medicine, IL; 5MedImmune, Ltd., Cambridge, UK
Background/Objective: AD is a chronic inflammatory skin disease characterized by increased interleukin (IL)-13 levels. Tralokinumab, an anti-IL-13 monoclonal antibody, has shown efficacy and an acceptable safety profile in patients with severe, uncontrolled asthma driven by the T-helper 2 pathway. Serum dipeptidyl peptidase 4 (DPP-4) has been reported as a predictive marker for tralokinumab in patients with severe asthma. Here, we evaluated whether tralokinumab offers therapeutic benefit to adults with moderate-to-severe AD.
Methods: In this Phase IIb, randomized, placebo-controlled, double-blind study (NCT02347176), patients were randomized 1:1:1:1 to receive tralokinumab 45mg, 150mg, or 300mg, or placebo every two weeks with mid-strength topical corticosteroids (TCS) for 12 weeks. Coprimary endpoints were change from baseline in Eczema Area Severity Index (EASI) and percentage of patients with clear or almost clear Investigator’s Global Assessment (IGA 0/1) at Week 12. Further efficacy, patient-reported outcomes, serum biomarkers, and safety endpoints were assessed.
Results: Overall, 204 patients were randomized. Tralokinumab 300mg treatment significantly reduced EASI scores (adjusted mean [standard error] change from baseline: 15.7 [1.3]; p=0.011) vs. placebo (-10.8 [1.4]) and more patients had IGA 0/1 (26% vs. 12%). Significant improvements were observed in patients who received tralokinumab 300mg versus placebo for Scoring of Atopic Dermatitis (p=0.002), Dermatology Life Quality Index (p=0.006), Pruritus Numeric Rating Scale (p=0.002), EASI75 (p=0.003), and EASI50 (p=0.025). Tralokinumab 300mg significantly reduced the number of Staphylococcus aureus-colonized patients (p=0.015), the concentration of serum immunoglobulin E, periostin, and TARC/CCL17, dose-dependently versus placebo (p<0.001). Patients with increased IL-13 activity (n=102), identified by baseline serum DPP-4 concentrations above median, showed an increased response to tralokinumab 300mg; more patients achieved IGA 0/1 (35% vs. 8%) and EASI75 (52% vs. 13%) than patients receiving placebo. The most frequent adverse events in all groups were nasopharyngitis (17%), upper respiratory tract infection (9%), headache (6%) and AD (6%).
Conclusion: Tralokinumab with TCS was more efficacious than TCS alone and demonstrated clinically relevant efficacy and an acceptable safety profile in patients with moderate-to-severe AD. DPP-4 might become a predictive marker for patients with AD who respond to tralokinumab 300mg, allowing a personalized medicinal approach.
Funding: This study was funded by MedImmune.