Atopic dermatitis (AD) involves barrier defects of the epidermis as well as skin inflammation and is often characterised by a debilitating itch. The role of interleukin-1 alpha (IL-1⍺) is not yet completely understood. “It is not clear what role IL-1⍺ plays in skin, but it is already an important player in oncology,” said Prof. Eric Simpson (Oregon Health & Science University, USA) during his presentation . Upon mechanical skin irritation or keratinocyte rupture, IL-1⍺ is released, leading to migration of leucocytes into the skin with consecutive inflammation. Once released, IL-1⍺ is also thought to induce a potentiation in sensory neurons; thus, contributing to pain and itch. It also provokes matrix metalloproteinases, entailing a breakdown of the skin barrier.
The new anti-IL-1⍺ antibody bermekimab binds to all forms of IL-1⍺ and neutralises it without targeting IL-1ß. A total of 38 patients with moderate-to-severe AD who did not show adequate response to topical corticosteroids were included in the trial. After a washout phase, they received weekly subcutaneous injections of 200 mg or 400 mg of bermekimab. The treatment period lasted 4 (200 mg) or 7 (400 mg) weeks with follow-up until week 9. Primary endpoint was drug safety and tolerability. Secondary endpoints included multiple disease severity measurements.
The higher dose showed to be more effective: mean clinical improvement assessed by different AD scores including EASI (Eczema Area and Severity Index), SCORAD (Severity Scoring of Atopic Dermatitis), GISS (Global Individual Signs Score), and IGA (Investigator Global Assessment) was 51% in the 400 mg cohort compared with 17% in the 200 mg group. Significant improvements were seen in all single scores. In addition, quality of life, assessed by the DLQI (Dermatology Life Quality Index), improved by 70%. At week 7, 25% of patients treated with 400 mg had a ≥2-point amelioration in IGA reaching nearly clear or clear skin (IGA 0/1). At this time, 82% of patients achieved an improvement of the EASI score by 50%, and 71% of patients had a 75% improvement in the EASI score.
Rapid itch reduction
In addition, bermekimab showed a remarkable antipruritic effect: 75% of patients treated with the higher dose reached a ≥4-point reduction on a numerical rating scale (NRS) for worst itch, and average itch scores at weeks 7 were also lower compared with baseline. “Targeting IL-1⍺ with this drug in adults with moderate-to-severe AD really showed a nice early signal for improved signs and symptoms. The rapid reduction in itch and pain may be caused by the role of IL-1⍺ in nerve potentiation,” suggested Prof. Simpson. Drug related toxicities were not apparent, but injection site reactions occurred in 3 patients. Based on the results, bermekimab will be further investigated in phase 3 studies as a novel treatment for AD.
- Simpson E. Abstract 11191, AAD Annual Meeting, 1-5 March 2019, Washington DC, USA.