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
https://www.researchgate.net/scientific-contributions/38161119_Alice_B_Gottlieb
Conference
28th European Academy of Dermatology and Venerology (EADV) Congress 2019, Madrid, Spain
Conference Date
09/10/2019

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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