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

Expert Name
Prof. Alice Gottlieb
Expert Affiliation
Icahn School of Medicine at Mount Sinai, USA
Expert Google Scholar or Orcid Url
28th European Academy of Dermatology and Venerology (EADV) Congress 2019, Madrid, Spain
Conference Date

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%.

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.

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

1 Gottlieb AB, et al. Late-breaking abstract D3T01.1F, EADV 2019, 9-13 Oct, Madrid, Spain.

2 Zebda R, Paller AS. J Am Acad Dermatol 2018;78 (3 Suppl 1):S43-52.

3 Schafer PH, et al. Cell Sign 2014;26:2016-9.

4 Simpson EL, et al. J Investig Dermatol 2019;139:1063-72.

5 Woo TE, et al. Skin Therapy Lett 2019;24:4-6.

6 McInnes IB, et al Arthritis Research & Therapy 2019:21:183.

7 Bissonnette R, et al. Br J Dermatol 2016;175:902-11.

8 Guttman-Yassky E, et al. J Am Acad Dermatol 2019;80:913-21.

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