Lebrikizumab significantly improves moderate-to-severe atopic dermatitis in adults and adolescents, according to study findings published in reported in the New England Journal of Medicine.
Researchers conducted a 52-week, randomized, double-blind, placebo-controlled, parallel-group ADvocate1 (trial 1) and ADvocate2 (trial 2) studies assessed the efficacy and safety of lebrikizumab monotherapy in patients with moderate-to-severe atopic dermatitis. Eligible participants were adults (ages, ≥18 years) and adolescents (ages, 12 to <18 years: weight, ≥40 kg).
The participants were randomly assigned in a 2:1 ratio to receive either lebrikizumab 250 mg with a 500-mg loading dose at baseline and week 2, or placebo, both of which were administered subcutaneously every 2 weeks. The primary efficacy outcome was an Investigator’s Global Assessment score of 0 or 1 with a decrease of at least 2 points at week 16.
Trial 1 enrolled patients from September 24, 2019, to February 26, 2021, and trial 2 enrollment took place between October 29, 2019, and March 19, 2021. In trial 1, 424 participants were randomly assigned to receive lebrikizumab (283 patients) or placebo (141). Their mean age was 35.5±17.3 years, 55 (13.0%) were adolescents, and 214 (50.5%) were girls or women. In trial 2, 427 patients were randomly assigned to receive lebrikizumab (281 patients) or placebo (146). Their mean age was 36.2±16.9 years, 47 (11.0%) were adolescents, and 211 (49.4%) were girls or women.
For trial 1, a primary outcome response occurred in 43.1% of participants who received lebrikizumab vs 12.7% who received placebo (P <.001). In trial 2, the percentages were 33.2% and 10.8%, respectively (P <.001).
The participants in the lebrikizumab group had a greater percentage of Eczema Area and Severity Index (EASI)-75 responses at week 16 compared with the placebo group participants in both trials. In trial 1, an EASI-75 response was reported in 58.8% of participants in the lebrikizumab group vs 16.2% in the placebo group (P <.001). In trial 2, the percentages were 52.1% and 18.1%, respectively (P <.001).
A significantly higher percentage of participants in the lebrikizumab group vs the placebo group in both trials had a decreased Pruritus Numeric Rating Scale score of at least 4 points at week 16 (P <.001 for both comparisons) and a decrease in the Sleep-Loss Scale score of at least 2 points from baseline at week 16 (P <.001 for both comparisons).
Adverse events in the induction period occurred in 129 of 282 participants (45.7%) who received lebrikizumab and in 73 of 141 participants (51.8%) who received placebo in trial 1, and in 150 of 281 (53.4%) and 96 of 145 (66.2%), respectively, in trial 2. Most of the events were mild-to-moderate in severity. The most common event that occurred in at least 5% of participants who received lebrikizumab and was consistently more frequent vs the placebo group was conjunctivitis (7.4% vs 2.8% in trial 1 and 7.5% vs 2.1% in trial 2).
Limitations of the trials include the induction period of 16 weeks in the 2 trials, which limited evaluations of efficacy and safety of longer-term treatment.
“These results show a rapid onset of action in multiple domains of the disease, such as skin clearance and itch,” conclude the researchers. “These results confirm the findings from the phase 2 trials of lebrikizumab.”
Disclosure: This research was supported by Dermira, a wholly owned subsidiary of Eli Lilly. Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Silverberg JI, Guttman-Yassky E, Thaçi D, et al. Two phase 3 trials of lebrikizumab for moderate-to-severe atopic dermatitis. N Engl J Med. 2023;388(12):1080-1091. doi:10.1056/NEJMoa2206714