Investigational systemic drugs for moderate to severe plaque psoriasis: What’s new?

ABSTRACT

Introduction

The therapeutic armamentarium for the treatment of psoriasis, a chronic inflammatory skin disease, is now reasonably broad and structured, with several therapeutic agents that demonstrated a successful long-term control of this condition. However, there are still unfulfilled gaps resulting from the inherent limitations of existing therapies, which have paved the way for the identification of new therapeutic strategies or the improvement of the existing ones.

Areas covered

The aim of this review is to thoroughly explore new therapeutic strategies and novel drugs that are currently in the pipeline for the treatment of psoriasis, focusing primarily on agents that are currently in phase I/II of clinical development. Some of which retrace already existing therapeutic approaches, such as the IL23/Th17 pathway inhibition, while others unveil new and yet unexplored ones.

Expert opinion

Since the therapeutic landscape of psoriasis is wide, it is not yet clear whether novel agents will fill the remaining gaps in the context of a broader and more diversified set of oral and biologic therapies. Nevertheless, with the development of precision medicine approaches, the development of innovative targeted drugs will still have a therapeutic rationale in psoriasis.

KEYWORDS:

• Biologics
• JAK inhibitors
• IL-17 inhibitors
• IL-12/23 inhibitors
• monoclonal antibodies
• clinical trial
• plaque psoriasis
• small molecules
• systemic treatments

Article highlights

• Psoriasis is a highly prevalent chronic inflammatory skin disease. In recent years, deeper understanding of the molecular and cellular pathways involved in pathophysiology has led to the emergence of highly effective targeted therapeutic drugs with potential for enhanced disease control.

• Novel drugs, currently under investigation in phase I and II trials, explore existing therapeutic targets, such as the IL-23/Th17 pathway inhibition, phosphodiesterase-4, and JAK inhibitors, along with new unexplored ones, including retinoic acid receptor-related orphan receptor γt (RORγt) and Heat Shock Protein (HSP)90 inhibitors.

• Whether the preliminary results achieved by these new agents will be confirmed in phase III studies, future treatment scenarios may rely on a diversified armamentarium with a more diversified set of oral and biologic therapies to help the physician personalize the therapeutic approach.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.