Andreas Wollenberg1, Michael D Howell2, Emma Guttman-Yassky3, Jonathan I Silverberg4, Christopher Kell5, Koustubh Ranade2, Rachel Moate6, René van der Merwe7. 1. Department of Dermatology and Allergy, Ludwig Maximillian University, Munich, Germany. Electronic address: wollenberg@lrz.uni-muenchen.de. 2. Translational Medicine, MedImmune, Gaithersburg, Md. 3. Department of Dermatology, Icahn School of Medicine at the Mount Sinai Medical Center Medicine, New York, NY. 4. Department of Dermatology, Preventive Medicine and Medical Social Sciences, Northwestern University Feinberg School of Medicine, Chicago, Ill. 5. Product Development, MedImmune, Cambridge, United Kingdom. 6. Clinical Statistics and Data, MedImmune, Cambridge, United Kingdom. 7. Clinical Respiratory Management, MedImmune, Cambridge, United Kingdom.
Abstract
BACKGROUND:IL-13 has an important role in atopic dermatitis (AD) pathogenesis. Tralokinumab is a fully human mAb that potently and specifically neutralizes IL-13. OBJECTIVE: We sought to evaluate the efficacy and safety of tralokinumab in adults with moderate-to-severe AD. METHODS: In this phase 2b study (NCT02347176), 204 adults were randomized 1:1:1:1 to receive 45, 150, or 300 mg of subcutaneous tralokinumab, or placebo, every 2 weeks for 12 weeks with concomitant topical glucocorticoids. Coprimary end points were change from baseline in Eczema Area Severity Index score and percentage of participants with an Investigator's Global Assessment response (0/1 score and reduction of ≥2 grades from baseline) at week 12. RESULTS: At week 12, 300 mg of tralokinumab significantly improved change from baseline in Eczema Area Severity Index score versus placebo (adjusted mean difference, -4.94; 95% CI, -8.76 to -1.13; P = .01), and a greater percentage of participants achieved an Investigator's Global Assessment response (26.7% vs 11.8%). Greater responses were found in participants with greater concentrations of biomarkers of increased IL-13 activity. Participants treated with 300 mg of tralokinumab demonstrated improvements in SCORAD, Dermatology Life Quality Index, and pruritus numeric rating scale (7-day mean) scores versus placebo. Upper respiratory tract infection was the most frequent treatment-emergent adverse event reported as related to study drug in the placebo (3.9%) and pooled tralokinumab (3.9%) groups. CONCLUSIONS:Tralokinumab treatment was associated with early and sustained improvements in AD symptoms and an acceptable safety and tolerability profile, thereby providing evidence for targeting IL-13 in patients with AD.
RCT Entities:
BACKGROUND:IL-13 has an important role in atopic dermatitis (AD) pathogenesis. Tralokinumab is a fully human mAb that potently and specifically neutralizes IL-13. OBJECTIVE: We sought to evaluate the efficacy and safety of tralokinumab in adults with moderate-to-severe AD. METHODS: In this phase 2b study (NCT02347176), 204 adults were randomized 1:1:1:1 to receive 45, 150, or 300 mg of subcutaneous tralokinumab, or placebo, every 2 weeks for 12 weeks with concomitant topical glucocorticoids. Coprimary end points were change from baseline in Eczema Area Severity Index score and percentage of participants with an Investigator's Global Assessment response (0/1 score and reduction of ≥2 grades from baseline) at week 12. RESULTS: At week 12, 300 mg of tralokinumab significantly improved change from baseline in Eczema Area Severity Index score versus placebo (adjusted mean difference, -4.94; 95% CI, -8.76 to -1.13; P = .01), and a greater percentage of participants achieved an Investigator's Global Assessment response (26.7% vs 11.8%). Greater responses were found in participants with greater concentrations of biomarkers of increased IL-13 activity. Participants treated with 300 mg of tralokinumab demonstrated improvements in SCORAD, Dermatology Life Quality Index, and pruritus numeric rating scale (7-day mean) scores versus placebo. Upper respiratory tract infection was the most frequent treatment-emergent adverse event reported as related to study drug in the placebo (3.9%) and pooled tralokinumab (3.9%) groups. CONCLUSIONS:Tralokinumab treatment was associated with early and sustained improvements in AD symptoms and an acceptable safety and tolerability profile, thereby providing evidence for targeting IL-13 in patients with AD.
Authors: Sebastian Strubl; Jacob A Torres; Alison K Spindt; Hannah Pellegrini; Max C Liebau; Thomas Weimbs Journal: Cell Signal Date: 2020-04-20 Impact factor: 4.315