Inhibition of IL-13: A New Pathway for Atopic Dermatitis

被引:20
作者
Ratnarajah, Kayadri [1 ]
Le, Michelle [2 ]
Muntyanu, Anastasiya [2 ]
Mathieu, Steve [3 ]
Nigen, Simon [4 ]
Litvinov, Ivan V. [2 ]
Jack, Carolyn S. [2 ]
Netchiporouk, Elena [2 ]
机构
[1] Univ Laval, Fac Med, Quebec City, PQ, Canada
[2] McGill Univ, Div Dermatol, Ctr Hlth, Montreal, PQ, Canada
[3] Univ Laval, Div Dermatol, Quebec City, PQ, Canada
[4] Maisonneuve Rosemont Hosp, Div Dermatol, Montreal, PQ, Canada
关键词
lebrikizumab; tralokinumab; IL13; atopic dermatitis;
D O I
10.1177/1203475420982553
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
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.
引用
收藏
页码:315 / 328
页数:14
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