Improvement Across Dimensions of Disease with Lebrikizumab Use in Atopic Dermatitis: Two Phase 3, Randomized, Double-Blind, Placebo-Controlled Monotherapy Trials (ADvocate1 and ADvocate2)

Eric Simpson; Pablo Fernández-Peñas; Marjolein de Bruin-Weller; Peter A Lio; Chia-Yu Chu; Khaled Ezzedine; Helena Agell; Marta Casillas; Yuxin Ding; Fan Emily Yang; Evangeline Pierce; Thomas Bieber

doi:10.1007/s12325-024-02974-y

Improvement Across Dimensions of Disease with Lebrikizumab Use in Atopic Dermatitis: Two Phase 3, Randomized, Double-Blind, Placebo-Controlled Monotherapy Trials (ADvocate1 and ADvocate2)

Adv Ther. 2024 Sep 9. doi: 10.1007/s12325-024-02974-y. Online ahead of print.

Authors

Affiliations

¹ Oregon Health & Science University, Portland, OR, USA. simpsone@ohsu.edu.
² Westmead Hospital, Sydney Medical School, The University of Sydney, Sydney, Australia.
³ National Expertise Center of Atopic Dermatitis, University Medical Center Utrecht, Utrecht, The Netherlands.
⁴ Northwestern University, Chicago, IL, USA.
⁵ National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
⁶ Henri Mondor University Hospital and Université Paris-Est Créteil University, Créteil, France.
⁷ Almirall, S.A., Barcelona, Spain.
⁸ Eli Lilly and Company, Indianapolis, IN, USA.
⁹ University Hospital Bonn, Bonn, Germany.

PMID: 39249591
DOI: 10.1007/s12325-024-02974-y

Abstract

Introduction: Atopic dermatitis is a complex, chronic, inflammatory skin disease that requires long-term control of symptoms like itch and sleep loss and improvement in quality of life, in addition to reduction of clinical signs. Lebrikizumab is a selective interleukin-13 inhibitor approved in the European Union, United Kingdom, United Arab Emirates, Canada, and Japan for treatment of moderate-to-severe atopic dermatitis in adults and adolescents. Here, we assess the magnitude of changes across signs and symptoms of atopic dermatitis with lebrikizumab monotherapy over the 16-week induction period in two phase 3 studies, ADvocate1 and ADvocate2.

Methods: Eligible adults (aged ≥ 18 years) and adolescents (aged 12 to < 18 years and weighing ≥ 40 kg) with moderate-to-severe atopic dermatitis were randomized to receive either 250 mg of lebrikizumab or placebo subcutaneously every two weeks. Least squares mean percentage change from baseline through week 16 was compared between lebrikizumab and placebo using mixed model repeated measure analysis for the following endpoints: Eczema Area and Severity Index (EASI), Pruritus Numeric Rating Scale (NRS), Sleep-Loss Scale, Patient-Oriented Eczema Measure (POEM), and Dermatology Life Quality Index (DLQI).

Results: In both trials, significant (P < 0.05) improvements were observed for lebrikizumab treatment compared with placebo at each 2-week timepoint for EASI, Pruritus NRS, Sleep-Loss Scale, and POEM, and at each 4-week timepoint for DLQI, through week 16. Statistically significant (P < 0.001) improvements were observed at 16 weeks for lebrikizumab treatment versus placebo in ADvocate1/ADvocate2 for EASI (71.9%/75.0% vs. 35.6%/43.3%), Pruritus NRS (53.3%/46.3% vs. 21.4%/18.0%), Sleep-Loss Scale (57.7%/55.6% vs. 23.9%/25.5%), POEM (54.4%/45.8% vs. 18.8%/16.9%), and DLQI (64.2%/60.5% vs. 28.5%/32.2%). Patient photos show improvements in skin appearance when disease measures improve.

Conclusions: Lebrikizumab monotherapy resulted in significant and fast improvements in multiple dimensions of disease (clinical signs, symptoms, and quality of life) over 16 weeks in patients with moderate-to-severe atopic dermatitis.

Trial registration: ClinicalTrials.gov identifiers, NCT04146363; NCT04178967.

Keywords: Atopic dermatitis; Itch; Lebrikizumab; Patient-reported outcomes; Quality of life; Skin; Sleep.

Associated data

ClinicalTrials.gov/NCT04146363
ClinicalTrials.gov/NCT04178967