Efficacy and safety of lebrikizumab (an anti-IL-13 monoclonal antibody) in adults with moderate-to-severe atopic dermatitis inadequately controlled by topical corticosteroids: A randomized, placebo-controlled phase II trial (TREBLE)

J Am Acad Dermatol. 2018 May;78(5):863-871.e11. doi: 10.1016/j.jaad.2018.01.017. Epub 2018 Jan 17.

Abstract

Background: Interleukin (IL)-13 plays a key role in type 2 inflammation and is an emerging pathogenic mediator in atopic dermatitis (AD).

Objective: We investigated the efficacy and safety of lebrikizumab, an IL-13 monoclonal antibody, as an add-on to topical corticosteroid (TCS) treatment.

Methods: A randomized, placebo-controlled, double-blind, phase 2 study. Adults with moderate-to-severe AD were required to use TCS twice daily and then randomized (1:1:1:1) to lebrikizumab 125 mg single dose, lebrikizumab 250 mg single dose, lebrikizumab 125 mg every 4 weeks for 12 weeks, or placebo every 4 weeks for 12 weeks, after a 2-week TCS run-in. The primary endpoint was percentage of patients achieving Eczema Area and Severity Index (EASI)-50 at week 12.

Results: In total, 209 patients received the study drug. At week 12, significantly more patients achieved EASI-50 with lebrikizumab 125 mg every 4 weeks (82.4%; P = .026) than placebo every 4 weeks (62.3%); patients receiving a single dose of lebrikizumab showed no statistically significant improvements in EASI-50 compared with placebo. Adverse events were similar between groups (66.7% all lebrikizumab vs 66.0% placebo) and mostly mild or moderate.

Limitations: Protocol-mandated twice daily TCS treatment limits our understanding of the efficacy of lebrikizumab as a monotherapy. The short study duration did not enable long-term efficacy or safety evaluations.

Conclusion: When combined with TCS, lebrikizumab 125 mg taken every 4 weeks led to a significant improvement and was well tolerated in patients with moderate-to-severe AD.

Keywords: EASI; anti-IL-13; atopic dermatitis; lebrikizumab; pruritus; topical corticosteroids.

Publication types

  • Clinical Trial, Phase II
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Administration, Topical
  • Adrenal Cortex Hormones / therapeutic use*
  • Adult
  • Antibodies, Monoclonal / therapeutic use*
  • Dermatitis, Atopic / diagnosis*
  • Dermatitis, Atopic / drug therapy*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Humans
  • Interleukin-13 / immunology
  • Male
  • Middle Aged
  • Patient Safety
  • Prognosis
  • Retreatment
  • Severity of Illness Index
  • Treatment Failure
  • Treatment Outcome

Substances

  • Adrenal Cortex Hormones
  • Antibodies, Monoclonal
  • Interleukin-13
  • lebrikizumab