Lebrikizumab effectively improves moderate to severe atopic dermatitis in phase 3 trial

A new study published in The New England Journal of Medicine suggests that 16 weeks of lebrikizumab medication proved efficacious in adolescents and adults with mild-to-severe atopic dermatitis during the induction period of two phase 3 studies.

The interleukin-4R-interleukin-13R1 heterodimer receptor signaling complex is prevented by lebrikizumab, a high-affinity IgG4 monoclonal antibody targeting interleukin-13. Jonathan Silverberg and colleagues worked on this two-phase trial to investigate the effectiveness of Lebrikizumab on moderate to severe Atopic Dermatitis.

Researchers performed two 52-week, double-blind, randomized, placebo-controlled phase 3 studies, each with a 16-week induction phase and a 36-week maintenance term. Eligible patients with moderate-to-severe atopic dermatitis (adults [18 years old] and adolescents [12 to 18 years old, weighing 40 kg]) were randomly randomized in a 2:1 ratio to receive lebrikizumab at a dosage of 250 mg (loading dose of 500 mg at baseline and week 2) or placebo, delivered subcutaneously every 2 weeks. The induction period's outcomes were evaluated up to 16 weeks and have been incorporated into this study.

The primary goal was to achieve an Investigator's Global Assessment (IGA) score of 0 or 1 (meaning clear or nearly clear skin; range, 0 to 4 [severe illness]) with a decrease (showing improvement) of at least 2 points from baseline at week 16. Secondary objectives were a 75% recovery in the Eczema Area and Severity Index (EASI-75 response) and itch and itch interference with sleep evaluations. Safety was also evaluated.

The key findings of this study were:

In study 1, 43.1% of 283 patients in the lebrikizumab group and 12.7% of 141 patients in the placebo group attained the main endpoint; an EASI-75 response occurred in 58.8% and 16.2%, respectively (P0.001).

The main endpoint in trial 2 was met in 33.2% of 281 patients in the lebrikizumab group and 10.8% of 146 patients in the placebo group (P0.001); an EASI-75 response occurred in 52.1% and 18.1%, respectively (P0.001).

Lebrikizumab medication improved itch and itch interference with sleep.

Conjunctivitis was more common in patients who got lebrikizumab than in those who received placebo.

The majority of adverse events throughout the induction phase were mild to moderate in severity and did not result in trial termination.

Reference:

Silverberg, J. I., Guttman-Yassky, E., Thaçi, D., Irvine, A. D., Stein Gold, L., Blauvelt, A., Simpson, E. L., Chu, C.-Y., Liu, Z., Gontijo Lima, R., Pillai, S. G., & Seneschal, J. (2023). Two Phase 3 Trials of Lebrikizumab for Moderate-to-Severe Atopic Dermatitis. In New England Journal of Medicine (Vol. 388, Issue 12, pp. 1080–1091). Massachusetts Medical Society. https://doi.org/10.1056/nejmoa2206714