Original article
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)

https://doi.org/10.1016/j.jaad.2018.01.017Get rights and content
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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.

Key words

anti-IL-13
atopic dermatitis
EASI
lebrikizumab
pruritus
topical corticosteroids

Abbreviations used

AD
atopic dermatitis
ADIQ
Atopic Dermatitis Impact Questionnaire
AE
adverse event
BSA
body surface area
EASI
Eczema Area and Severity Index
IGA
Investigator Global Assessment
IL-4
interleukin-4
IL-13
interleukin-13
SCORAD
SCORing Atopic Dermatitis
TCS
topical corticosteroids
VAS
Visual Analog Scale

Cited by (0)

Drs Simpson and Flohr contributed to this manuscript equally.

Funding sources: Funded by Genentech, a member of the Roche Group. Editorial assistance was provided by Wemimo Omotosho, PhD, of MediTech Media, funded by Genentech. Dr Flohr is funded through a National Institute for Health Research (NIHR) Career Development Fellowship (CDF-2014-07-037), and also supported by the NIHR Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King's College London.

Conflicts of interest: Dr Simpson reports grants, personal fees, and nonfinancial support from Roche-Genentech during the conduct of the study; personal fees from AbbVie, Celgene, Dermira, Galderma, LEO Pharma, Menlo Therapeutics, Sanofi Genzyme, and Valeant Pharmaceutical; grants and personal fees from Anacor Pharma, GlaxoSmithKline, and Regeneron Pharmaceuticals; grants from MedImmune, Novartis, Roivant Sciences, Tioga Pharmaceuticals, and Vanda Pharmaceuticals; and grants and personal fees from Eli Lilly outside the submitted work. Dr Flohr reports personal fees from Sanofi Regeneron outside the submitted work. The views expressed are those of the author(s), and not necessarily those of the UK NIHR or the UK Department of Health. Dr Eichenfield reports personal fees and nonfinancial support from Roche-Genentech during the conduction of the study and the following activities: Sanofi Regeneron (investigator, consultant, speaker); Cutanea (consultant); Dermavant (investigator); Eli Lilly (consultant); Galderma (investigator, consultant); Anacor/Pfizer (investigator, consultant); Novartis (consultant); LEO (investigator, consultant); Medimetriks (consultant); and Valeant (investigator, consultant). Dr Bieber has the following declaration of interests: Roche (consultant); Sanofi Regeneron (investigator, consultant, speaker); Eli Lilly (investigator, consultant, speaker); Galderma (investigator, consultant); Pfizer (investigator, consultant); Novartis (investigator, consultant); GlaxoSmithKline (consultant, speaker); LEO (investigator, consultant, speaker); and AbbVie (consultant). Dr Sofen reports personal fees from Genentech during the conduction of the study and personal fees from Regeneron and LEO outside the submitted work. Dr Taïeb has nothing to disclose. Drs Owen, Putnam, DeBusk, Lin, and Omachi are employees of Genentech, a member of the Roche group, and have a patent pending. Dr Yen is an employee of Roche and has a patent pending. Dr Voulgari is an employee of Roche Products Ltd.

Previously presented: Data from this study were presented at the European Academy of Dermatology and Venereology in Vienna, Austria on October 1, 2016.

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