A new class of biologic agents facing the therapeutic paradigm in psoriasis: anti-IL-23 agents.

ABSTRACT

Introduction: Psoriasis is a chronic inflammatory skin disease whose pathogenesis is driven by multiple cytokine-mediated pathways. In this immunologic setting, the centrality of the IL-23/IL-17 axis and its therapeutic relevance has emerged.

Areas covered: This review is aimed at collecting preliminary data on IL23p19 blockers developed for the treatment of plaque psoriasis. Three agents, guselkumab, risankizumab, and tildrakizumab, are currently being tested in phase III trials, while LY2525623 is currently being tested in phase II trials. Treatment with these agents resulted in a marked improvement in disease severity, confirming the pathogenic relevance of IL-23 in psoriasis.

Expert opinion: Selective neutralization of IL-23 is an advantageous strategy for treating psoriasis. Preliminary data from phase II and III trials have shown the capability of this therapeutic class in inducing complete clearance or almost complete clearance in many patients: the highest PASI 90 rates were achieved by guselkumab, tildrakizumab, and risankizumab in 73.3%, 74% and 77% of cases, respectively. Moreover, the highest PASI 100 rates were achieved in 33%, 14%, and 48% of patients treated with guselkumab, tildrakizumab, and risankizumab, respectively. Further studies are needed to confirm this remarkable efficacy over long-term treatment periods.

KEYWORDS:

• Psoriasis
• risankizumab
• tildrakizumab
• guselkumab
• LY2525623
• pathogenesis
• IL-23
• IL-17

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Corrigendum

Declarations of interest

A Chiricozzi is a consultant for Novartis, Leo Pharma, Eli Lilly and Company and AbbVie, companies which produce and/or commercialize the products mentioned herein. … The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Article highlights

• Variously lines of evidence have highlighted that IL-23 is central to psoriasis pathogenesis

• Four agents targeting the IL-23p19 subunit (i.e., guselkumab, risankizumab, tildrakizumab, and LY 2,525,623) have been developed for the treatment of plaque psoriasis

• Phase II and phase III trials investigating IL-23 blockers have shown remarkable efficacy, with the highest PASI 90 rates achieved by guselkumab, tildrakizumab, and risankizumab in 73.3%, 74% and 77% of cases, respectively. Moreover, the highest PASI 100 rates were achieved in 33%, 14%, and 48% of patients treated with guselkumab, tildrakizumab, and risankizumab, respectively

• Phase II and phase III trials have also reported a favorable safety profile primarily characterized by non-serious adverse events, detecting nasopharyngitis and upper respiratory tract infections as the most common adverse events

• Head-to-head studies testing IL-23 blockers vs. active comparators have demonstrated their superior efficacy compared to current and previously marketed biologics.

• Long-term observation is necessary, as exclusively short-term data evaluating limited drug exposures are currently available

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Funding

This manuscript has not been funded.