IL-1⍺ blockade: a new treatment option in AD

IL-1⍺ blockade is a novel interesting target in atopic dermatitis (AD). In a proof-of-concept study, an IL-1 blocker improved AD in all disease measures [1].

“The rationale behind targeting IL-1⍺ is that Th1 immunity plays a signifying role in adults with chronic AD,” said Prof. Alice Gottlieb (Icahn School of Medicine at Mount Sinai, USA). Under the influence of a variety of cytokines, including IL-17A and IL-17C, keratinocytes increase release of IL-1⍺. This cytokine drives leukocyte recruitment and activates the vascular endothelium [2]. By potentiation of nociceptors, itch is increased. It stimulates expression of matrix metalloproteinases, thus impairing the skin barrier [3]. This results in skin inflammation, epidermal barrier defects, and severe, debilitating itch, and these factor are all hallmarks of AD [4,5]. IL-1⍺ on circulating leukocytes may also drive inflammatory signalling in the microvasculature of lesions. In addition, it induces breakdown of the skin barrier by prompting matrix metalloproteinases. In animal studies, IL-1⍺ has shown to induce pruritus [6].

Therefore, an open-label, proof-of-concept, multicentre study evaluated the safety and efficacy of bermekimab, a monoclonal antibody targeting IL-1⍺, in patients with moderate-to-severe AD [1]. Participants were treated with 200 mg bermekimab (n=10) or 400 mg bermekimab (n=28). Injections were given weekly for 4 or 8 weeks, respectively.

After 8 weeks, patients treated with 400 mg bermekimab achieved an improvement in the EASI by 75% from baseline, and a reduction in the Scoring of Atopic Dermatitis (SCORAD) by 67% (both differences P<0.0001). In addition, patients gained a significant better quality of life: 61% of patients in the high-dose group ended with a Dermatology Life Quality Index score of 0/1, which means that the disease no longer has an impact on their quality of life. Overall, 80% of patients treated with the higher dose achieved an improvement in pruritus (worst and average itch) scores on a Numeric Rating Scale of ≥ 4 points (see Figure). Significant improvements were also seen in anxiety and depression. At the beginning of the study, 71% of patients said they had a pain score of 7 out of 10. After 8 weeks, this was improved by more than 80%.

Figure: 80% of patients achieved a ≥4 points reduction in the worst and average itch NRS score [1]



There were 25 non-serious adverse events, which included no major adverse cardiac events and no neoplasms. Injection-site reactions were reported by 3%. The 400 mg dose provided greater efficacy without an increase in side effects. “The only side effects we noticed were grade 1 injection site reactions and nausea in 3 subjects. This surely is early data but it is still a nice study,” concluded Prof. Gottlieb.

1. 
   
   1. Gottlieb AB, et al. Late-breaking abstract D3T01.1F, EADV 2019, 9-13 Oct, Madrid, Spain.
   2. Guttman-Yassky E, Krüger JG. J Invest Dermatol 2018;138:1467-69.
   3. Guttman-Yassky E, Krüger JG. Curr Opin Immunol 2017;48:68-73.
   4. Gittler JK, et al. J Allergy Clin Immunol 2013;131:300-13.
   5. Yarbrough KB, et al. Dermatol Ther 2013;26:110-9.
   6. Katayama I, et al. J Invest Dermatol Symp Proc 2001;6:81-6.

 



Posted on 9 December 201912 March 2021