Efficacy and safety of lebrikizumab in moderate-to-severe atopic dermatitis: 52-week results of two randomized double-blinded placebo-controlled phase III trials.

Abstract

BACKGROUND:

Lebrikizumab is a novel, high-affinity monoclonal antibody that selectively binds to interleukin (IL)-13.

OBJECTIVES:

To evaluate the efficacy and safety of lebrikizumab monotherapy in adolescent and adult patients with moderate-to-severe atopic dermatitis (AD) over 52 weeks of treatment in ADvocate1 (NCT04146363) and ADvocate2 (NCT04178967).

METHODS:

Patients who responded to lebrikizumab 250 mg every 2 weeks (Q2W) at the end of the 16-week induction period were re-randomized 2 : 2 : 1 to receive lebrikizumab Q2W, lebrikizumab 250 mg every 4 weeks (Q4W) or placebo Q2W (lebrikizumab withdrawal) for 36 additional weeks. Response at week 16 was defined as achieving a 75% reduction in Eczema Area Severity Index (EASI 75) or an Investigator's Global Assessment (IGA) of 0 or 1, with a ≥ 2-point improvement and no rescue medication use. Multiple imputation was used to handle missing data. Intermittent use of topical therapy was permitted during the maintenance period.

RESULTS:

After 52 weeks, an IGA of 0 or 1 with a ≥ 2 point improvement was maintained by 71.2% of patients treated with lebrikizumab Q2W, 76.9% of patients treated with lebrikizumab Q4W and 47.9% of patients in the lebrikizumab withdrawal arm. EASI 75 was maintained by 78.4% of patients treated with lebrikizumab Q2W, 81.7% of patients treated with lebrikizumab Q4W and 66.4% of patients in the lebrikizumab withdrawal arm at week 52. Across treatment arms, proportions of patients using any rescue therapy were 14.0% (ADvocate1) and 16.4% (ADvocate2). During the combined induction and maintenance periods of ADvocate1 and ADvocate2, 63.0% of lebrikizumab-treated patients reported any treatment emergent adverse event, with most events (93.1%) being mild or moderate in severity.

CONCLUSIONS:

After a 16-week induction period with lebrikizumab Q2W, lebrikizumab Q2W and Q4W maintained similar improvement of the signs and symptoms of moderate-to-severe AD, with a safety profile consistent with previously published data.

• Authors: Andrew Blauvelt, Jacob P Thyssen, Emma Guttman-Yassky, Thomas Bieber, Esther Serra-Baldrich, Eric Simpson, David Rosmarin, Hany Elmaraghy, Eric Meskimen, Chitra R Natalie, Zhuqing Liu, Chenjia Xu, Evangeline Pierce, MaryAnn Morgan-Cox, Esther Garcia Gil, Jonathan I Silverberg
• Journal: The British journal of dermatology (Br J Dermatol) Vol. 188 Issue 6 Pg. 740-748 (05 24 2023) ISSN: 1365-2133 [Electronic] England
• PMID: 36994947 (Publication Type: Randomized Controlled Trial, Clinical Trial, Phase III, Journal Article)
• Copyright: © The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists.

Chemical References

• lebrikizumab
• Antibodies, Monoclonal, Humanized
• Antibodies, Monoclonal
• Interleukin-13
• Immunoglobulin A

Topics

• Adult
• Adolescent
• Humans
• Dermatitis, Atopic (drug therapy, diagnosis)
• Antibodies, Monoclonal, Humanized
• Treatment Outcome
• Injections, Subcutaneous
• Double-Blind Method
• Severity of Illness Index
• Antibodies, Monoclonal (adverse effects)
• Interleukin-13
• Immunoglobulin A