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

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.

Immunobiologicals and ocular surface disease

“…Another placebo-controlled phase 2b clinical trial evaluating the efficacy and safety of lebrikizumab in AD demonstrated that, at 16 weeks, Eczema Area and Severity Index (EASI) and Investigator's Global Assessment (IGA) were achieved by 60.6 and 44.6% of patients taking lebrikizumab at its highest dose (versus 24.3 and 15.3% of patients taking placebo, respectively). Moreover, treatment with lebrikizumab was associated with a rapid improvement of pruritus and low rates of conjunctivitis (1.4–3.8%) [22].…”

The hidden sentinel of the skin: An overview on the role of interleukin-13 in atopic dermatitis

“…After binding to its receptor IL-13Rα1, IL-13 activates sensory neurons acting as an enhancer of other stimuli such as histamine ( 44 ). However, IL-13 is a potent neuroactive cytokine that potentiates also the responses of nonhistaminergic itch pathways ( 45 ). For example, it is involved in a histamine-independent direct stimulation of afferent nerve endings mediated by transient receptor potential ankyrin 1 (TRPA1) pathway ( 45 ).…”

Clinical trials of antibody drugs in the treatments of atopic dermatitis

“…In addition, Lebrikizumab is another humanized mAb against IL-13 which has passed phase 2 trials ( 55 ). Comparing with the other monoclonal antibodies that targeted IL-13, the probability of adverse effects caused by this drug is lower ( 56 ). For instance, there is a potentially lower rate of conjunctivitis (1.4–3.8%) in lebrikinumab-treated patients compared to those used dupilumab.…”