Psoriasis: New treatments and current pipeline

In the last few years, new treatment options have been developed based on new insights into the pathophysiology of psoriasis.

In the pathophysiology of psoriasis, dendritic cells are thought to orchestrate and steer the inflammatory process via the release of cytokines [1,2]. One of these prominent cytokines is IL-23, which stimulates T cells. Upregulation of IL-17 is viewed as a central element. In the presence of tumour necrosis factor (TNF), IL-17 is the strongest activator of keratinocyte function. Cytokines produced by keratinocytes signal back to T cells and dendritic cells. “This vicious circle is viewed to contribute to the chronicity of the disease,” Prof. Kristian Reich (Dermatologikum Hamburg, Germany) explained.

Recently, Prof. Reich and colleagues showed that IL-23 is produced by inflammatory monocytes; not by dendritic cells [3]. In addition, TNF is produced by dendritic cells, and IL-17 by T cells. It becomes increasingly clear that both IL-17A and IL-17F have a pro-inflammatory role in the pathogenesis of psoriasis [4]. “But they don’t come from the same cells” Prof. Reich added. “There is evidence that more types of innate immune cells, such as γδ T cells, type 3 innate lymphoid cells, and neutrophils, synthesise IL-17, and that this process is not controlled by IL-23.”

Targeted therapies

These insights are important as “one of the new treatment modalities we now get – in addition to the existing IL-17A blockers – are molecules that also block IL-17F,” Prof. Reich elaborated. Previous research demonstrated that IL-17A was absent in healthy skin but upregulated in psoriasis, while IL-17F is present in normal skin and upregulated in psoriasis, likely contributing to inflammation [5]. To normalise both IL-17A and IL-17F in psoriasis, IL-17A and IL-17F should be downregulated in different degrees.

A head-to-head trial, recently published in the New England Journal of Medicine, showed that bimekizumab (anti-IL-17A/F) resulted in significantly higher Psoriasis Area and Severity Index (PASI) scores compared with secukinumab (anti-IL-17A) in plaque psoriasis [6]. Furthermore, results recently published in The Lancet on the IL-17A/F nanobody sonelokimab were “impressive,” according to Prof. Reich. Interestingly, Candida rates in phase 2 studies showed dramatic differences: 13.4% with bimekizumab and only 5.2% with sonelokimab [8,9]. “Obviously, the nanobody has a more differentially inhibitory effect and is likely blocking IL-17A more than IL-17F,” Prof. Reich concluded.

1. Reich K. New treatments/pipeline psoriasis. 6^th World Psoriasis & Psoriatic Arthritis Conference, 30 June–3 July 2021.
2. Hawkes JE, et al. J Allergy Clin Immunol. 2017;140:645–53.
3. Mehta H, et al. J Invest Dermatol. 2021;141:1707–18.
4. Reich K, et al. Exp Dermatol. 2015;24:529–35.
5. Kolbinger F, et al. J Allergy Clin Immunol. 2017;139:923–32.
6. Reich K, et al. N Engl J Med. 2021;385:142–52.
7. Papp KA, et al. Lancet. 2021;397:1564–75.
8. Papp KA, et al. J Am Acad Dermatol. 2018;79:277–86.
9. Blauvelt A, et al. J Am Acad Dermatol. 2020;83:1367–74.

 

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Posted on 17 September 202129 February 2024