Lebrikizumab improves EASI, pruritus in adults with atopic dermatitis
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The novel interleukin 13 inhibitor lebrikizumab improved skin lesions, pruritis and quality of life among adults with moderate to severe atopic dermatitis, according to data from a phase 2b trial published in JAMA Dermatology.
“There are two important findings from this study. First, [the results] provide a new treatment that is safe for atopic dermatitis patients and shows a hint that maybe it can be given every 4 weeks, which is important,” Emma Guttman-Yassky, MD, PhD, of the department of dermatology at Icahn School of Medicine at Mount Sinai, told Healio. “But beyond that, it provides a very targeted treatment to patients and answers a very important question: which cytokine is the most important? The answer is that IL-13 is likely the most important cytokine for atopic dermatitis, otherwise we would not see such major efficacy by solely targeting IL-13.”
Guttman-Yassky and colleagues conducted a randomized, double-blind, placebo-controlled, dose-ranging study from Jan. 23, 2018, to May 23, 2019, to examine the use of lebrikizumab (Dermira) injections every 2 weeks or every 4 weeks. The primary endpoint was percent change in Eczema Area and Severity Index (EASI) from baseline to 16 weeks. Secondary endpoints were Investigator’s Global Assessment score of 0 or 1 (IGA 0/1); 50%, 75% or 90% improvement in EASI from baseline; percent change in pruritus numeric rating scale (NRS); and a 4-point or higher improvement in pruritus NRS score. The researchers also tracked treatment-related adverse events.
Participants included 280 adults with a mean age of 39 years who were randomly assigned to placebo (n = 52), 125 mg lebrikizumab every 4 weeks (n = 73), 250 mg lebrikizumab every 4 weeks (n = 80) or 250 mg lebrikizumab every 2 weeks (n = 75).
Lebrikizumab was associated with statistically significant, dose-dependent improvements in EASI from baseline to week 16 compared with placebo (EASI least squares mean [SD] percent change): –62.3% [37.3%] for the 125 mg every 4 weeks group (P = .02), –69.2% [38.3%] for the 250 mg every 4 weeks group (P = .002) and –72.1% [37.2%] for the 250 mg every 2 weeks group (P < .001) vs. –41.1% [56.5%] for placebo.
Compared with placebo, statistically significantly more patients in the 250 mg lebrikizumab dose groups achieved IGA 0/1: 15.3% for placebo vs. 33.7% for 250 mg every 4 weeks and 44.6% for 250 mg every 2 weeks; EASI50: 45.8% for placebo vs. 77% for 250 mg every 4 weeks and 81% for 250 mg every 2 weeks; EASI75: 24.3% for placebo vs. 56.1% for 250 mg every 4 weeks and 60.6% for 250 mg every 2 weeks; and EASI90: 11.4% for placebo vs. 36.1% for 250 mg every 4 weeks and 44% for 250 mg every 2 weeks.
Patients measured pruritus daily via an 11-point NRS, and more patients in the treatment groups experienced a reduction in itch severity of at least four points compared with placebo: 41.8% for the 125 mg every 4 weeks group, 47.4% for the 250 mg every 4 weeks group and 70% for the 250 mg every 2 weeks group (P < .001) vs. 27.3% for placebo.
Lebrikizumab is a monoclonal antibody designed to bind to IL-13 to prevent the formation of the IL-13 receptor alpha/IL-4 receptor alpha heterodimer complex and signaling, according to a company press release. The investigational drug received fast track designation from the FDA in December 2019.
“If these findings replicate in phase 3 studies, lebrikizumab may meaningfully advance the standard of care for moderate to severe AD. Taken together, the broad and robust improvements in AD clinical manifestations observed with lebrikizumab, along with its favorable safety profile, suggest that it may be an efficacious and well-tolerated treatment for moderate to severe AD. A follow-up phase 3 program was initiated in October 2019 to evaluate long-term efficacy and safety of lebrikizumab, maintenance therapy regimens and therapeutic use in younger patients,” Guttman-Yassky and colleagues wrote in the study. – by Stacey L. Adams with additional reporting by Kate Burba
Disclosures: Guttman-Yassky reports receiving research funds (grants paid to Icahn School of Medicine) from AbbVie, Almirall, Amgen, AnaptysBio, Asana Biosciences, Boehringer-Ingelheim, Celgene, Dermavant, DS Biopharma, Eli Lilly, Galderma, Glenmark, Innovaderm, Janssen Pharmaceuticals, Kiniksa, Kyowa Kirin, Leo Pharma, Novan, Pfizer, Ralexar, Regeneron, Sienna Biopharma, UCB and Union Therapeutics and serving as a consultant for AbbVie, Almirall, Amgen, Asana BioSciences, Boehringer-Ingelheim, Cara Therapeutics, Celgene, Concert, DBV, Dermira, Inc, DS Biopharma, Eli Lilly, EMD Serono, Escalier, Galderma, Glenmark, Kyowa Kirin, Leo Pharma, Mitsubishi Tanabe, Pfizer, RAPT Therapeutics, Regeneron, Sanofi, Sienna Biopharma and Union Therapeutics. Please see the study for all other authors’ relevant financial disclosures.
Perspective
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Peter A. Lio, MD
The biologic revolution for atopic dermatitis began with the approval of dupilumab in 2017 but continues to heat up with an exciting pipeline of agents that hold much promise. While dupilumab (Dupixent, Regeneron) binds to the IL-4 receptor alpha interfering with both IL-4 and IL-13 binding, lebrikizumab targets soluble IL-13, ultimately blocking downstream signaling, while tralokinumab — still another biologic in development for AD — binds IL-13 in a manner that blocks both IL-13 signaling and endogenous IL-13 regulation. What is remarkable is that despite differences in target as well as mechanism compared to dupilumab, the results of this study suggest a robust effect on the signs and symptoms of AD. For clinicians and patients, this suggests there will be multiple options for treating AD, and as we learn more about these new agents, we may find special considerations and key differences to guide their individual selection.
References:
Bagnasco D, et al. Int Arch Allergy Immunol. 2016;170:122-131.
Moyle M, et al. Exp Dermatol. 2019;28:756-768.
Popovic B, et al. J Mol Biol. 2017;429:208-219.
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