96 Tralokinumab significantly reduces Staphylococcus aureus colonization in adult patients with moderate-to-severe atopic dermatitis (AD): Results from a Phase 2b, randomized, double-blind, placebo-controlled study (NCT02347176)

摘要

Introduction: AD flares are associated with increased Staphylococcus aureus colonization, which may amplify cutaneous inflammatory responses via release of staphylococcal superantigens and toxins. Tralokinumab, a fully human monoclonal antibody targeting inter-leukin-13, improved Eczema Area and Severity Index, Investigator Global Assessment, and SCORing Atopic Dermatitis score in patients with moderate-to-severe AD on a topical corticosteroids (TCS) background in a Phase 2b study. This exploratory analysis evaluated the effect of tralokinumab treatment on eliminating S. aureus colonization. Methods: Patients with AD for >1 year and moderate-to-severe AD were randomized 1:1:1:1 to receive subcutaneous tralokinumab (45, 150, or 300 mg) or placebo every 2 weeks for 12 weeks on a TCS background. Lesional and non-lesional skin was swabbed at baseline and week 12 to identify patients positive for S. aureus. The difference in S. aureus-positive patients between baseline and week 12 was analyzed using logistic regression, or unconditional exact method if the number of responders was <5 in any treatment arm. Results: 204 patients were randomized; 51:50:51:52 in the pla-cebo:45 mg:150 mg:300 mg groups, respectively. At baseline, 74.5% (placebo), 68.0% (45 mg), 74.0% (150 mg), and 67.3% (300 mg) of patients were S. aureus-positive. The percentage of S. aureus-positive patients at week 12 was significantly lower in all three tralokinumab groups vs placebo in lesional skin, with percentage differences (95% Cl) of -31.6% (-50.5, -12.6; P = 0.002 [45 mg]), -36.4% (-54.8, -18.0; P< 0.001 [150 mg]), and -38.3% (-56.6, -20.0; P < 0.001 [300 mg]). The percentage of patients with a shift from S. aureus-positive at baseline to S. aureus-negative at 12 weeks was higher in all tralokinumab groups vs placebo in lesional skin, with 36.2% (45 mg), 40.8% (150 mg), and 43.8% (300 mg) of patients, vs only 14.9% in the placebo group. Conclusions: Tralokinumab+TCS treatment significantly reduced S. aureus colonization over placebo+TCS in lesional skin, with the largest improvement in the tralokinumab 300 mg group. These results suggest that specific neutralization of interleukin-13 with tralokinumab reduces S. aureus colonization, potentially leading to fewer skin infections and AD flares.