Comparative Efficacy of Lebrikizumab, Dupilumab, and Tralokinumab in Maintaining Treatment Response in Atopic Dermatitis at Varying Treatment Continuance Rates

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Jonathan Silverberg
Alan Irvine
Peter Foley
James Del Rosso
Luis Puig
Linda Stein Gold
Martin Dossenbach
Marta Casillas
Gaia Gallo
Buelent Akmaz
Kim Rand

Keywords

atopic dermatitis, lebrikizumab, dupilumab, tralokinumab

Abstract

Introduction: Atopic dermatitis (AD) is a chronic inflammatory skin disease with significant impacts on quality of life. Despite the effectiveness of biologics for moderate to severe AD, long-term treatment adherence can be challenging in clinical practice. This study introduces the “durability index” as a novel estimate of the maintenance of therapeutic effect under varying treatment continuance rates.


Methods: A population-adjusted indirect comparison of placebo-controlled phase 3 trials of dupilumab 300 mg QW/Q2W (SOLO 1, SOLO 2, and SOLO CONTINUE), tralokinumab 300 mg Q2W (ECZTRA1 and ECZTRA 2), and lebrikizumab 250 mg Q4W (ADvocate1 and ADvocate2) was conducted. In these trials, patients who responded at week 16 (IGA 0/1 or EASI 75) were re-randomized to either continue treatment or switch to treatment withdrawal (placebo) until week 52. The durability index was developed to estimate drug performance at varying treatment continuance rates between 100% to 0% on-treatment. Unanchored simulated treatment comparison (STC) was used to estimate odds ratios (OR) adjusting for baseline covariates.


Results: For IGA 0/1, patients receiving lebrikizumab had statistically significantly better odds of maintaining response at week 52 than those on dupilumab for all treatment continuance rates, ranging from 1.730 (p = 0.044) at 100% to 4.690 (p < 0.001) at 0%. ORs comparing lebrikizumab to tralokinumab ranged from 1.787 at 100% continuance to 1.516 at 0%, with significant results favoring continuance rates between 39.5% and 96.9%. For EASI 75, week-52 durability at 100% continuance was non-significantly different between lebrikizumab and dupilumab (OR 0.687, p = 0.183); however, ORs increased in favor of lebrikizumab at lower treatment continuance rates, reaching significance from 64.2% (OR 1.454, p = 0.05) to 0% (OR 3.235, p < 0.001) continuance. ORs comparing lebrikizumab to tralokinumab ranged from 2.132 at 100% to 3.891 at 0% continuance, with significant results favoring lebrikizumab for all treatment continuance rates. ORs comparing dupilumab and tralokinumab showed varying results: tralokinumab was favored for IGA 0/1 at lower continuance rates, while dupilumab was favored for EASI 75 at higher continuance rates.


Conclusions: In this indirect comparative analysis, lebrikizumab had treatment response rates that were comparable to or better than dupilumab and tralokinumab, regardless of treatment continuance rates. This finding suggests that lebrikizumab may offer a more effective long-term management option for AD.


This analysis was funded by Eli Lilly and Company.

References

1. Hosoya K, et al. Patient Prefer Adherence. 2023;17:861-872.

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4. Worm M, et al. JAMA Dermatol. 2020;156(2):131-143.

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