Clinical pharmacokinetics and pharmacodynamics of oral systemic nonbiologic therapies for psoriasis patients

ABSTRACT

Introduction

Psoriasis is a chronic inflammatory immune condition. Treatments for psoriasis vary with disease severity, ranging from topicals to systemic biologic agents. The pharmacokinetic (PK) and pharmacodynamic (PD) properties of these therapies establish drug efficacy, toxicity, and optimal dosing to ensure therapeutic drug levels are sustained and adverse effects are minimized.

Areas Covered

A literature search was performed on PubMed, Google Scholar, and Ovid MEDLINE for PK and PD, efficacy, and safety data regarding oral systemic nonbiologic therapies utilized for moderate-to-severe plaque psoriasis. The findings were organized into sections for each drug: oral acitretin, methotrexate, cyclosporine, apremilast, tofacitinib, and deucravacitinib.

Expert Opinion

Some psoriasis patients may not respond to initial therapy. Ongoing research is evaluating genetic polymorphisms that may predict an improved response to specific medications. However, financial and insurance barriers, as well as limited genetic polymorphisms correlated with treatment response, may restrict the implementation of genetic testing necessary to personalize treatments. How well psoriasis patients adhere to treatment may contribute greatly to variation in response. Therapeutic drug monitoring may help patients adhere to treatment, improve clinical response, and sustain disease control.

KEYWORDS:

• Nonbiologic
• oral
• psoriasis
• safety
• pharmacokinetics
• pharmacodynamics

Article highlights

• Oral nonbiologic systemic treatments can be used to treat moderate-to-severe plaque psoriasis.

• The pharmacokinetic and pharmacodynamic properties of oral systemic agents help determine their efficacy, toxicity, and dosing.

• Oral acitretin is a well-tolerated drug with common but usually mild adverse effects such as cheilitis, skin peeling, pruritus, alopecia, and rhinitis.

• Methotrexate and cyclosporine carry risk of liver and renal toxicity, respectively.

• Apremilast is more efficacious than methotrexate with an improved safety profile and no need for laboratory monitoring.

• Tofacitinib is a Janus kinase inhibitor and deucravacitinib is a more selective TYK2 inhibitor. Both are efficacious in the treatment of plaque psoriasis and psoriatic arthritis with common adverse effects of nasopharyngitis and upper respiratory infection.

Declaration of interest

S Feldman has received research, speaking and/or consulting support from Eli Lilly and Company, GlaxoSmithKline/Stiefel, AbbVie, Janssen, Alovtech, vTv Therapeutics, Bristol-Myers Squibb, Samsung, Pfizer, Boehringer Ingelheim, Amgen, Dermavant, Arcutis, Novartis, Novan, UCB, Helsinn, Sun Pharma, Almirall, Galderma, Leo Pharma, Mylan, Celgene, Ortho Dermatology, Menlo, Merck & Co, Qurient, Forte, Arena, Biocon, Accordant, Argenx, Sanofi, Regeneron, the National Biological Corporation, Caremark, Teladoc, BMS, Ono, Micreos, Eurofins, Informa, UpToDate and the National Psoriasis Foundation. He is founder and part owner of Causa Research and holds stock in Sensal Health. The other 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.