Inhibition of IL-13: A New Pathway for Atopic Dermatitis [Formula: see text].

Abstract

Dupilumab, a monoclonal antibody against the common receptor of interleukin (IL)-4 and IL-13, was the first biologic therapy approved in Canada for treatment of moderate-to-severe atopic dermatitis (AD). While it is considered safe and effective, dupilumab is not universally effective and 8%-38% of patients develop conjunctivitis, while some patients develop head and neck dermatitis. Thus, new therapeutic options are warranted. While both IL-4 and IL-13 play important roles in the pathogenesis of AD, it has been recently demonstrated that IL-13 is the primary upregulated cytokine in AD skin biopsy samples. A placebo-controlled phase 2b clinical trial evaluating the efficacy and safety of lebrikizumab, an IL-13 inhibitor, in AD demonstrated that, at 16 weeks, Eczema Area and Severity Index (EASI) 75 and Investigator's Global Assessment (IGA) 0/1 were achieved by 60.6% and 44.6% of patients taking lebrikizumab at its highest dose (vs 24.3% and 15.3% of patients taking placebo, respectively). Moreover, treatment with lebrikizumab was associated with rapid improvement of pruritus and low rates of conjunctivitis (1.4%-3.8%). Another IL-13 monoclonal antibody, tralokinumab, was evaluated for safety and efficacy in moderate-to-severe AD. By week 12, among adults receiving 300 mg tralokinumab, 42.5% achieved EASI-75 and 26.7% achieved IGA 0/1 score (vs 15.5% and 11.8% in the placebo group, respectively). Both lebrikizumab and tralokinumab demonstrated acceptable safety profiles in AD (and non-AD) trials with adverse events often being comparable between treatment and control groups. Thus, IL-13 inhibitors may provide a safe and effective treatment alternative for patients with moderate-to-severe AD.

• Authors: Kayadri Ratnarajah, Michelle Le, Anastasiya Muntyanu, Steve Mathieu, Simon Nigen, Ivan V Litvinov, Carolyn S Jack, Elena Netchiporouk
• Journal: Journal of cutaneous medicine and surgery (J Cutan Med Surg) 2021 May-Jun Vol. 25 Issue 3 Pg. 315-328 ISSN: 1615-7109 [Electronic] United States
• PMID: 33350863 (Publication Type: Journal Article, Review)

Chemical References

• Antibodies, Monoclonal
• Interleukin-13
• tralokinumab
• lebrikizumab

Topics

• Antibodies, Monoclonal (therapeutic use)
• Dermatitis, Atopic (drug therapy)
• Humans
• Interleukin-13 (antagonists & inhibitors)