Mechanistic Understanding of Clinical Response to Bimekizumab in Psoriatic Disease

Use of bimekizumab, a monoclonal immunoglobulin G1 (IgG1) antibody that selectively inhibits the cytokine interleukin-17F (IL-17F), in addition to IL-17A, has been shown to result in a rapid response and prolonged, high-level disease control in patients with moderate-to-severe plaque psoriasis. At the 2024 European Academy of Dermatology and Venereology (EADV) Congress, an oral presentation and a poster were presented related to furthering the understanding of the mechanisms that lead to the clinical response observed with bimekizumab. The oral presentation examined the effects of bimekizumab on subcomponents of the Psoriasis Area and Severity Index (PASI). Analyses showed ≥95% mean improvement in erythema, thickness, and scaling with bimekizumab by Week 12 of treatment, which was maintained to Week 48. Bulk transcriptomic analysis showed complete normalisation of gene signatures associated with these subcomponents by Week 8, preceding clinically apparent skin clearance. A poster presented at the 2023 5th Inflammatory Skin Diseases (ISDS) focused on the effect of bimekizumab on tissue-resident memory T (TRM­) cells, which have been associated with disease perpetuation during treatment and with psoriasis recurrence at the same location following treatment withdrawal. Bulk transcriptomic analyses showed normalisation of a TRM gene signature at Week 8 after only two doses of bimekizumab, as well as normalised expression of pro-survival factors that may be prolonging survival of pathogenic TRM cells and pathogenic IL-17A/F-secreting cells. These results may have implications for disease modification and help explain the long-term durability of response observed with bimekizumab. The results shown in the oral presentation and poster support the rationale for initiation of the BE UNIQUE study, the protocol for which was reported at EADV 2024. This ongoing, multicentre, Phase IIIb study is recruiting patients with moderate-to-severe plaque psoriasis, with or without concomitant active psoriatic arthritis, with a primary objective to assess change in composite gene expression score at Week 48. This study aims to further elucidate the molecular mechanisms underlying the rapid, high-level, and durable clinical responses observed with bimekizumab.