618 - A Bayesian network meta-analysis comparing the efficacy of dupilumab versus tralokinumab in adults with severe atopic dermatitis with inadequate response or intolerance to cyclosporin A
Authors: Guyot Patricia , Chandrasekhar Boya , Chiricozzi Andrea , Gianluca Ronci , Mariapaola Pedone , Noonan Kerry , Wang Zhixiao 
Published: August 2024

Abstract

Background
Cyclosporin A (CSA), approved in some countries in the European Union for treating severe AD, is associated with nephrotoxicity and hypertension that limit its long-term use. Biologic agents, such as dupilumab and tralokinumab, approved by the United States Food and Drug Administration for the treatment of uncontrolled moderate-to-severe AD, are associated with consistent symptomatic improvement over long-term use, either with or without concomitant topical corticosteroids (TCS).

Objectives
To evaluate the efficacy of dupilumab/TCS vs tralokinumab/TCS using placebo/TCS as a common comparator in adult patients with AD with inadequate response to CSA or for whom CSA treatment was medically inadvisable.

Methods
LIBERTY AD CAFÉ (NCT02755649) and a subgroup of LIBERTY AD CHRONOS (NCT02260986; inadequate response/medically inadvisable to CSA) were pooled. This pooled data (CAFÉ + CAFÉ-CHRONOS-LIKE [CCL]) comparing dupilumab/TCS vs placebo/TCS and ECZTRA 7 (NCT03761537) clinical trial comparing tralokinumab/TCS vs placebo/TCS were included in the network meta-analysis (NMA). Difference in mean change from baseline (CFB) for Eczema Area and Severity Index (EASI) score, Peak Pruritus Numeric Rating Scale (PP-NRS), and odds of achieving EASI 50, EASI 75, EASI 90, ≥ 4-point improvement in PP-NRS and Investigator’s Global Assessment of clear/almost clear skin score (IGA 0/1) were the efficacy endpoints included in the analysis. Mean difference in CFB in the Dermatology Life Quality Index (DLQI) was also included as a quality-of-life endpoint. Dichotomous endpoints were expressed as odds ratio (OR). The number needed to treat (NNT) for achieving dichotomous endpoints were computed to compare treatment benefits. Continuous outcomes were expressed as difference in mean CFB. All the endpoints were assessed at Week 16. An indirect treatment comparison was performed using the WinBugs software to perform Bayesian NMA with fixed effects model method using 95% credible interval (CrI).

Results
A total of 576 patients (ECZTRA: placebo: 137; tralokinumab: 140; CCL: placebo: 169; dupilumab: 130) were included in the NMA. Improvement in EASI, PP-NRS and DLQI measured by mean difference in CFB was significantly higher for dupilumab/TCS, compared to tralokinumab/TCS at week 16 (mean difference in CFB for EASI [─ 9.46 {95% credible interval, CrI: ─ 13.37, ─ 5.54}]; PP-NRS: ─ 0.87; [─ 1.67, ─ 0.07], and DLQI: ─ 3.38; [─ 5.20, ─ 1.56]. Compared to placebo/TCS, the odds for achieving EASI 50 (OR: 4.68; [2.15, 10.43]), EASI 75 (OR: 2.92; [1.46, 5.87]), EASI 90 (OR: 4.81; [2.18, 10.93]), ≥ 4-point improvement in PP-NRS (OR: 3.45; [1.62, 7.48]), and IGA 0/1 (OR: 2.60; [1.19, 5.79]) were also significantly higher with dupilumab/TCS vs tralokinumab/TCS. The NNT was lower with dupilumab/TCS vs tralokinumab/TCS for achieving EASI 50 (3 vs 8), EASI 75 (3 vs 7), EASI 90 (3 vs 12), ≥ 4-point improvement in PP-NRS (3 vs 12) and IGA 0/1 (3 vs 9).

Conclusions
This NMA suggests that treatment with dupilumab/TCS was associated with significant improvements in EASI, PP-NRS, DLQI, and IGA in comparison with tralokinumab/TCS. Dupilumab/TCS was also associated with lower NNT than tralokinumab/TCS, making it a valuable therapy in patients with severe AD.