Dupilumab Versus Lebrikizumab with Topical Corticosteroids: Efficacy in Atopic Dermatitis

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Dupilumab in combination with topical corticosteroids (TCS) is more likely to improve quality of life, signs, and symptoms of atopic dermatitis than lebrikizumab and TCS, according to recent findings.¹

These conclusions were presented at the 2024 Revolutionizing Atopic Dermatitis (RAD) 2024 Annual Meeting in Chicago, with the research having been led by Patricia Guyot, of Sanofi. Guyot and colleagues noted that both lebrikizumab and dupilumab are monoclonal antibodies which are known to be both efficacious and safe in treatment of individuals moderate-to-severe atopic dermatitis during clinical trials.

The investigators decided to compare the results of lebrikizumab, a humanized antibody which is designed to selectively target (IL)-13, and dupilumab, a fully human antibody designed to target both interleukin IL-4 and IL-13. A lack of prior direct, head-to-head clinical studies that looked at the efficacy results of dupilumab versus lebrikizumab alongside TCS was cited by the research team.

The team highlighted the fact that ‘Bucher indirect treatment comparisons’ (ITCs), designed to anchor medication effects to a common comparator such as a placebo, can allow for a reliable means of assessing the relative effectiveness of these types of treatments when there is a lack of direct comparison data available.

Consequently, Guyot et al. sought to assess the findings resulting from a placebo-adjusted Bucher ITC of therapy lasting 16-weeks for patients with moderate-to-severe eczema, or atopic dermatitis. These findings would compare dupilumab’s efficacy to that of lebrikizumab, administered every 2 weeks (Q2W) with TCS, respectively.

Design

The team’s placebo-adjusted Bucher ITC utilized data which had been drawn from the phase 3 LIBERTY AD CHRONOS and ADhere studies, aiming at a 16-week period employing non-responder imputation. Specifically, there had been a 300mg dupilumab dose and TCS Q2W, or placebo + TCS, and there was a 250mg dose of lebrikizumab Q2W + TCS, or placebo + TCS, respectively.

The investigators did not make adjustments for baseline characteristics, and outcomes measured included the following: the proportion of subjects showing an Investigator’s Global Assessment score of 0/1 (IGA-0/1; clear/almost clear), at least a 75% improvement from the point of baseline in the Eczema Area and Severity Index (EASI-75), a 4-point improvement from baseline in participants’ peak pruritus Numerical Rating Scale scores (PP-NRS ≥4), and an improvement of ≥4-points from the point of baseline in the Dermatology Life Quality Index (DLQI ≥4).

Findings

Those featured in the ADhere study were shown by the team to have lower atopic dermatitis severity versus LIBERTY AD CHRONOS participants on IGA, though they noted that scores on EASI, PP-NRS, and DLQI had been comparable across the 2 trials. The investigators reported that dupilumab combined with TCS surpassed lebrikizumab combined with TCS for all of the outcomes assessed, according to their placebo-adjusted Bucher ITC findings.

The research team noted that the OR for the IGA 0/1 and DLQI ≥4 endpoints of the study had also indicated dupilumab as the superior option, though statistical significance was not reached: DLQI ≥4 (OR=2.35, 95%CI 0.94–5.87) and IGA 0/1 (OR=1.90, 95%CI 0.81–4.42).Those in the dupilumab + TCS group were shown to be far more likely to reach EASI-75 (OR=2.39, 95%CI 1.10–5.19) as well as PP-NRS ≥4 (OR=2.63, 95%CI 1.17–5.95) by the 16-week mark, compared to those given lebrikizumab therapy + TCS.

Prior research, presented at the Revolutionizing Atopic Dermatitis 2023 Spring Conference, indicated that lebrikizumab and TCS could serve as a beneficial alternative for individuals with moderate to severe atopic dermatitis who had been unresponsive to treatment with dupilumab.² These new findings at RAD 2024 add to the body of data on these 2 treatment options for patients.

References

1. ^{Irvine A, Paller A, Cyr S, et al. Dupilumab demonstrates higher likelihood of achieving improvements in signs, symptoms, and quality of life vs lebrikizumab: results from a placebo-adjusted indirect comparison analysis. Revolutionizing Atopic Dermatitis (RAD) 2024 Annual Meeting June 8 – 10, 2024. Chicago, IL.}
2. ^{Gold LS, Gutermuth J, Adam D, Flohr C, et al. Lebrikizumab Providers Clinically Meaningful Improvements in Atopic Dermatitis in Patients Previously Treated with Dupilumab. Paper presented at: Paper presented at: Revolutionizing Atopic Dermatitis 2023 Spring Conference; April 29 – May 1, 2023; Washington, DC. Accessed April 30, 2023.}