Important and Upcoming Developments in Psoriasis

Psoriasis research is ever-evolving and expanding, with several new and upcoming treatment options and clinical or therapeutic developments on the horizon.

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Researchers conducted a review¹ of psoriasis literature in order to compile a list of developments, perspectives, and research on the disease. Review data was collected from prior research, reviews, and studies published in Journal der Deutschen Dermatologischen Gesellschaft (JDDG) over the course of 20 years.

As of the review’s publication earlier this month, JDDG has published content amassing several topic areas, including:

• Basic pathophysiologic aspects
• Diagnostic and clinical developments
• Epidemiological issues
• Health services research and registry studies
• Psychosocial aspects
• Recommendations for practical implementation of new findings
• Therapeutic approaches

“Central to our current understanding of the pathogenesis of psoriasis are close and complex interactions between components of the innate and adaptive immune systems,” review authors wrote. “Communication between these immune cells is mediated by various cytokines, chemokines, and other mediators. Among these, tumor necrosis factor alpha (TNF-α) and components of the interleukin (IL)-23/IL-17 axis, in particular, have been established as major pathogenesis-oriented therapeutic targets.”

Due to these understandings of pathogenesis, current, approved biologic treatment options for psoriasis in Germany and the US include adalimumab, certolizumab pegol, etanercept, and infliximab, all of which target against TNF-α. Golimumab, which also targets TNF-α, is approved only for the treatment of psoriatic arthritis.

In targeting IL-23 and IL-17, both Germany and the US have approved brodalumab, guselkumab, ixekizumab, rizankizumab, secukinumab, tildrakizumab, and ustekinumab.

In addition, bimekizumab is approved for psoriasis treatment in Germany, but is not in the US. Other biologics, including mirikizumab, sonelokimab, and netakimab are recent developments.

“In addition, small-molecule drugs have been and are being developed, for example, apremilast against phosphodiesterase 4 (PDE4), deucravacitinib against tyrosine kinase 2 (TYK2), and piclidenoson, a Gi protein-associated A3 adenosine receptor agonist,” review authors wrote. “It is conceivable that some modern therapies may even lead to fundamentally altered and normalized immune status (disease modification) and thereby to permanent remission of psoriasis, at least in some patients.”

Aside from pathogenesis-oriented therapeutics, antipsoriatic therapeutics have recently been taking on 2 routes: targeting or inhibiting additional mediators and attributing mediators to innate immune mechanisms, or developing oral, small-molecule compounds capable of entering cells.

Bimekizumab, an anti-body blocking both IL-17A and IL-17F, is just 1 recent example of the former. IL-36 antagonists, such as spesolimab, are recent developments which researchers said may have positive results in treating highly inflammatory or pustular psoriasis.

In September 2022, the US FDA approved TYK2 inhibitor deucravacitinib as an oral therapy for patients with moderate-to-severe psoriasis.

Despite review authors acknowledging the progress in psoriasis developments, they argue that there are several unmet areas that need further research and development. Some of these areas include:

• The development of drugs and treatments which take individual characteristics into account
• The interactions and roles of components of the immune system as they relate to disease expression
• Pathogenic significance of other tissue and cell types, as well as immunologic (dys)regulation
• Relationships between psoriasis and environmental factors, microbiota, and pathologic constitutions
• Pathogenically-relevant molecules evaluated as therapeutic targets on a subcellular level

“Through psoriasis research, we are gaining a better understanding of the interplay between the components of the innate and adaptive immune systems,” review authors wrote.

Reference

1. Schön MP, Wilsmann‐Theis D. Current developments and perspectives in psoriasis. JDDG: Journal der Deutschen Dermatologischen Gesellschaft. 2023. doi:10.1111/ddg.15033