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Clinical Pharmacokinetic and Pharmacodynamic Considerations in the Treatment of Moderate-to-Severe Psoriasis

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Abstract

Psoriasis is a common inflammatory immune disorder due to chronic activation of the adaptive and innate immune responses. Therapies for psoriasis target reducing inflammatory cytokines such as tumor necrosis factor-alpha, interleukin-17, and interleukin-22. Patients with inflammatory disorders have reduced metabolism by cytochrome P450 enzymes in the liver. The pharmacokinetic and pharmacodynamic changes due to psoriasis also have an impact on reaching therapeutic concentrations of the drug. Pharmacokinetic and pharmacodynamic data help determine the safety and clinical considerations necessary when utilizing drugs for plaque psoriasis. A literature search was performed on PubMed and Ovid MEDLINE for the pharmacokinetic and pharmacodynamic data of oral therapies and biologics utilized for moderate-to-severe plaque psoriasis. The findings from the literature search were organized into two sections: oral therapies and biologics. The pharmacokinetic and pharmacodynamic parameters in healthy patients, patients with psoriasis, and special populations are discussed in each section. The oral therapies described in this review include methotrexate, cyclosporine, apremilast, tofacitinib, and deucravacitinib. Biologics include tumor necrosis factor-alpha inhibitors, interleukin-17 inhibitors, ustekinumab, and interleukin-23 inhibitors. Clinical considerations for these therapies include drug toxicities, dosing frequency, and anti-drug antibodies. Methotrexate and cyclosporine have a risk for hepatoxicity and renal impairment, respectively. Moreover, drugs metabolized via cytochrome P450, including tofacitinib and apremilast have decreased clearance in patients with psoriasis, requiring dose adjustments. Patients treated with therapies such as adalimumab can develop anti-drug antibodies that reduce the long-term efficacy of the drug. Additionally, overweight patients benefit from more frequent dosing to achieve better psoriasis clearance.

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Fig. 1

Adapted from Reis, J., Vender, R., & Torres, T. (2019). Bimekizumab: the first dual inhibitor of interleukin (IL)-17A and IL-17F for the treatment of psoriatic disease and ankylosing spondylitis. BioDrugs, 33, 391-399. Licensing number: 5595510452417

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  1. Department of Dermatology, Center for Dermatology Research, Wake Forest University School of Medicine, 475 Vine St, Winston-Salem, NC, 27101, USA

    Jonathan Greenzaid & Steven Feldman

  2. Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, NC, USA

    Steven Feldman

  3. Department of Social Sciences & Health Policy, Wake Forest University School of Medicine, Winston-Salem, NC, USA

    Steven Feldman

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Steven 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 a founder and part owner of Causa Research and holds stock in Sensal Health. Jonathan Greenzaid has no conflicts of interest that are directly relevant to the content of this article.

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SF and JG contributed to the conception and design of the manuscript. JG collected, analyzed, and interpreted the data and drafted the manuscript. SF critically revised the manuscript and approved the final version to be published.

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Greenzaid, J., Feldman, S. Clinical Pharmacokinetic and Pharmacodynamic Considerations in the Treatment of Moderate-to-Severe Psoriasis. Clin Pharmacokinet 63, 137–153 (2024). https://doi.org/10.1007/s40262-023-01341-4

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