The use of lebrikizumab improves the symptoms of moderate-to-severe atopic dermatitis (AD) in patients previously treated with dupilumab, reports a study presented at AAD 2025.

“In this study, lebrikizumab resulted in clinically meaningful improvements in the symptoms of itch, itch interference on sleep, and skin pain in patients previously exposed to dupilumab,” said lead author Dr Gil Yosipovitch, University of Miami Miller School of Medicine, Miami, Florida, US.

This open-label, phase IIIb, 24-week study included 86 patients who ceased using dupilumab due to inadequate response (n=48, 56 percent), intolerance or adverse event (n=14, 16 percent), or other reasons (n=24, 28 percent). Eligible participants were administered lebrikizumab 250 mg every 2 weeks (Q2W) through week 16.

At week 16, patients who achieved an Investigator’s Global Assessment (IGA) score of 0/1 with ≥2-point improvement or at least a 75-percent improvement in the Eczema Area and Severity Index (EASI75) received lebrikizumab 250 mg every 4 weeks (Q4W) through week 24. The rest continued using lebrikizumab Q2W.

Yosipovitch and his team combined the data across lebrikizumab Q2W and Q4W, which were summarized as “observed” and with “nonresponder imputation/multiple imputation” (NRI/MI). They then assessed the following outcomes: Pruritus Numeric Rating Scale (PNRS), Sleep-Loss Scale, and Skin Pain NRS (assessed discomfort/soreness).

The proportion of patients who achieved a ≥3-point improvement in the PNRS was 72.9 percent (35/48) at week 16 and 77.5 percent (31/40) at week 24 observed, and 66.9 percent (42/63) and 63.6 percent (40/63) with NRI/MI, respectively. [AAD 2025, abstract 59618]

The percentage of those achieving a ≥4-point improvement in PNRS was 53.2 percent (25/47) at week 16 and 61.5 percent (24/39) at week 24 observed, and 48.8 percent (30/62) and 47.9 percent (30/62) with NRI/MI, respectively.

At weeks 16 and 24, the respective proportion of patients who achieved a ≥2-point improvement in Sleep-Loss Scale was 41.7 percent (10/24) and 42.1 percent (8/19) observed, and 33.6 percent (12/36) and 30.4 percent (11/36) with NRI/MI.

Finally, Skin Pain NRS ≥4-point improvement was reported in 58.8 percent (20/34) at week 16 and 75.0 percent (21/28) at week 24 observed, and 51.5 percent (24/47) and 55.9 percent (26/47), respectively, with NRI/MI.

Inadequate response

Furthermore, “lebrikizumab provided a clinically meaningful improvement in itch response for at least half of patients who discontinued dupilumab due to inadequate response,” Yosipovitch said. 

In patients who discontinued the use of dupilumab because of inadequate response, 65.2 percent (15/23) achieved a ≥3-point improvement and 50.0 percent (11/22) a ≥4-point improvement in the PNRS (observed) at week 16.

Of the 15 patients who achieved PNRS ≥3-point improvement, three had no response to dupilumab, seven had partial response, and five had lost response. Among those who achieved a ≥3-point improvement, one had no response to dupilumab, five had partial response, and five had lost response.

“Given the heterogeneity and dynamic nature of AD, patients may respond differently to lebrikizumab and dupilumab,” Yosipovitch said. [Am J Clin Dermatol 2022;23:459-468]

Although both agents inhibit interleukin-13 signalling, differences exist in their pharmacokinetics and mechanisms of action, according to the authors. [Drugs Context 2021;10:1-7; Allergol Int 2020;69:187-196]