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)

Eric Simpson, Carsten Flohr, Lawrence F. Eichenfield, Thomas Bieber, Howard Sofen, Alain Taïeb, Ryan Owen, Wendy Putnam, Marcela Castro, Kendra DeBusk, Chin Yu Lin, Athina Voulgari, Karl Yen, Theodore A. Omachi

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
JournalJournal of the American Academy of Dermatology
DOIs
StateAccepted/In press - Jan 1 2018

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Interleukin-13
Atopic Dermatitis
Adrenal Cortex Hormones
Monoclonal Antibodies
Placebos
Safety
Eczema
lebrikizumab
Inflammation

Keywords

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

ASJC Scopus subject areas

  • Dermatology

Cite this

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). / Simpson, Eric; Flohr, Carsten; Eichenfield, Lawrence F.; Bieber, Thomas; Sofen, Howard; Taïeb, Alain; Owen, Ryan; Putnam, Wendy; Castro, Marcela; DeBusk, Kendra; Lin, Chin Yu; Voulgari, Athina; Yen, Karl; Omachi, Theodore A.

In: Journal of the American Academy of Dermatology, 01.01.2018.

Research output: Contribution to journalArticle

Simpson, Eric ; Flohr, Carsten ; Eichenfield, Lawrence F. ; Bieber, Thomas ; Sofen, Howard ; Taïeb, Alain ; Owen, Ryan ; Putnam, Wendy ; Castro, Marcela ; DeBusk, Kendra ; Lin, Chin Yu ; Voulgari, Athina ; Yen, Karl ; Omachi, Theodore A. / 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). In: Journal of the American Academy of Dermatology. 2018.
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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.",
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T1 - Efficacy and safety of lebrikizumab (an anti-IL-13 monoclonal antibody) in adults with moderate-to-severe atopic dermatitis inadequately controlled by topical corticosteroids

T2 - A randomized, placebo-controlled phase II trial (TREBLE)

AU - Simpson, Eric

AU - Flohr, Carsten

AU - Eichenfield, Lawrence F.

AU - Bieber, Thomas

AU - Sofen, Howard

AU - Taïeb, Alain

AU - Owen, Ryan

AU - Putnam, Wendy

AU - Castro, Marcela

AU - DeBusk, Kendra

AU - Lin, Chin Yu

AU - Voulgari, Athina

AU - Yen, Karl

AU - Omachi, Theodore A.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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.

AB - 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.

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KW - EASI

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KW - pruritus

KW - topical corticosteroids

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