Lebrikizumab demonstrates strong phase 3 data for atopic dermatitis

Child itches atopic dermatitis on skin Image credit: © Марина Терехова - © Марина Терехова - stock.adobe.com

Lebrikizumab treatment led to substantial improvements for adolescents and adults with moderate-to-severe atopic dermatitis (AD), according to recent findings.

The drug—an IgG4 monoclonal antibody which targets interleukin-13—is known to stop the formation of interleukin-4Rα–interleukin-13Rα1 heterodimer receptor signaling complex.

Given that IL-13 is implicated as the primary cytokine for AD, and given that serum levels of IL-13 correlate with severity of the skin disease, this study was seen as important. It was authored by Jonathan I. Silverberg, MD, from the Department of Dermatology at George Washington University School of Medicine and Health Sciences.

“Here, we report the efficacy and safety outcomes from the first 16 weeks of two 52-week, phase 3 trials of lebrikizumab monotherapy: ADvocate1 and ADvocate2,” Silverberg and colleagues wrote.

Background and Findings

The investigators performed 2 identical, phase 3, randomized, double-blind, placebo-controlled, parallel-group trials over the course of 52 weeks to assess lebrikizumab monotherapy for both adults and adolescents.

The research team made each trial have 2 treatment periods, the first being a 16-week period of induction and the second being a 36-week maintenance period.

The investigators recruited participants with moderate-to-severe AD, including adults who were aged 18 years and above, and adolescents aged 12 to under 18 years with a body weight of 40 or more kg.

The team also randomly allocated the participants to be given either lebrikizumab at a dosage of 250 mg (500 mg loading dose at baseline and week 2) or the placebo. They administered the treatment subcutaneously every 2 weeks, assessing outcomes for up to 16 weeks during the induction period.

Overall, the investigators reported in trial 1, 43.1% of patients who had been given lebrikizumab met the primary outcome compared to 12.7% of patients given the placebo (Eczema Area and Severity Index score response for 58.8% versus 16.2%, respectively).

In the second trial, 33.2% of participants given lebrikizumab met the primary outcome compared to 10.8% of patients given the placebo (EASI-75 response in 52.1% versus 18.1%, respectively).

The investigators noted that lebrikizumab therapy led to improved itch and itch interference with sleep, although those given the therapy reported a higher incidence of conjunctivitis.

Lastly, the research team added that most adverse events were found to be mild or moderate in severity and that none resulted in discontinuation of the trial.

“The results from these trials, together with the available evidence showing the associations of interleukin-13 and interleukin-13–producing cells with clinical severity scores for atopic dermatitis, confirm the central role of interleukin-13 in the pathogenesis of this disease,” they wrote. “As compared with dupilumab, which binds to the interleukin-4Rα receptor subunit shared by the interleukin-4 and interleukin-13 receptor complexes, lebrikizumab and tralokinumab bind directly to interleukin-13.”

Reference

Silverberg JI, et al. Two Phase 3 Trials of Lebrikizumab for Moderate-to-Severe Atopic Dermatitis. N Engl J Med. 2023;388(11):1023-1034. doi: 10.1056/NEJMoa2206714.

This article was initially published by our sister publication HCP Live.