Eric L Simpson1, Carsten Flohr2, Lawrence F Eichenfield3, Thomas Bieber4, Howard Sofen5, Alain Taïeb6, Ryan Owen7, Wendy Putnam7, Marcela Castro7, Kendra DeBusk7, Chin-Yu Lin7, Athina Voulgari8, Karl Yen9, Theodore A Omachi10. 1. Department of Dermatology, School of Medicine, Oregon Health & Science University, Portland, Oregon. 2. St. John's Institute of Dermatology, King's College London and Guy's & St Thomas' NHS Foundation Trust, London, United Kingdom. 3. Department of Dermatology, University of California San Diego, San Diego, California. 4. Department of Dermatology and Allergy, University Medical Center, Bonn, Germany. 5. University of California Los Angeles School of Medicine, Los Angeles, California. 6. Department of Dermatology and Pediatric Dermatology, Bordeaux Hospital University Center, France. 7. Genentech, South San Francisco, California. 8. Global Product Development Clinical Science, Roche Products Limited, Welwyn Garden City, United Kingdom. 9. Roche, Grenzacherstrasse, Basel, Switzerland. 10. Genentech, South San Francisco, California. Electronic address: omachi.theodore@gene.com.
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.
RCT Entities:
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.
Authors: Sebastian Strubl; Jacob A Torres; Alison K Spindt; Hannah Pellegrini; Max C Liebau; Thomas Weimbs Journal: Cell Signal Date: 2020-04-20 Impact factor: 4.315
Authors: Steven R Feldman; Linda S Cox; Lindsay C Strowd; Robert A Gerber; Steven Faulkner; Debra Sierka; Timothy W Smith; Joseph C Cappelleri; Mark E Levenberg Journal: Am Health Drug Benefits Date: 2019-04