Pathogenesis-oriented therapy of psoriasis using biologics

ABSTRACT

Introduction

Psoriasis is currently regarded an immune-mediated inflammatory disease. The central pathogenic axis comprises interleukin-23, TH17-lymphocytes differentiating under its influence, and interleukin-17A as a key effector cytokine of these T-lymphocytes. All of these can selectively be targeted using biological therapies, thus potentially increasing efficacy and reducing adverse events when compared to conventional systemic therapeutics.

Areas covered

We review the current concept of psoriasis as an immune-mediated inflammatory disease, assessing the evidence for a role of elements of the innate and adaptive immune system. We then correlate the pharmacological effects of biologics in psoriasis in light of the known physiologic as well as pathophysiological role of the respective targets. This is done on the basis of an extensive literature search of publications since 2018 which describe the role of the above-mentioned elements in health and disease or the effects of blocking these as an attempt to treat psoriasis.

Expert opinion

Biologics targeting the above-mentioned central pathogenic axis provide a particularly effective and safe way to treat psoriasis. Given the impact of comorbidities on therapeutic decision-making, and the efficacy of some biologics also on certain comorbidities, these drugs represent a first step toward personalized medicine in the management of psoriasis.

KEYWORDS:

• Biologics
• comorbidity
• personalized medicine
• psoriasis
• regulatory T-lymphocytes
• TH17-lymphocytes
• therapy
• tissue-resident memory T-cells

Article highlights

• Psoriasis is currently regarded an immune-mediated inflammatory disease.

• The central pathogenic axis comprises interleukin (IL)-23, TH17-lymphocytes differentiating under its influence, and IL-17A as a key effector cytokine of these T-lymphocytes.

• Evidence suggests that other isoforms of IL-17, other cellular sources of IL-17, and additional cellular targets of IL-23 qualify as ‘druggable’ targets in the treatment of psoriasis.

• Biologics selectively targeting the above-mentioned elements are particularly effective in treating psoriasis.

• The physiological role of the targeted cytokines provides a basis to understand the safety profile and potential contraindications of the respective biologic.

• As several key elements of the central pathogenic axis of psoriasis are also involved in comorbidities of psoriasis, namely psoriatic arthritis and inflammatory bowel disease, the use of biologics to treat psoriasis represents a first step towards personalized medicine in the management of this disease.

Declaration of interest

WH Boehncke has received honoraria as a speaker and/or advisor from Abbvie, Almirall, Amgen, Bristol Myers Squibb, Celgene, Janssen, Leo, Lilly, Novartis, Pfizer, and Union Chimique Belge. 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.

Reviewer disclosures

A reviewer on this manuscript has disclosed that they have worked on clinical trials with all medications cited in this article and is an advisor or paid speaker for Abbvie, Amgen, Eli Lilly, and Bristol Myers Squibb. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.