clinical topic updates

Current Data on Interleukin-23 Inhibition in the Clinical Spectrum of Psoriasis

by Alice B. Gottlieb, MD, PhD

Overview

Interleukin 23 (IL-23) plays an important role in the development of psoriatic disease, and IL-23 inhibitors are effective and well tolerated for the treatment of patients with plaque psoriasis.

Expert Commentary

Alice B. Gottlieb, MD, PhD

Clinical Professor and Medical Director
Mount Sinai Beth Israel Hospital
Department of Dermatology
Icahn School of Medicine at Mount Sinai
New York, NY

“IL-23 blockers have emerged as effective and well-tolerated options for the treatment of moderate to severe plaque psoriasis. Their advantages are infrequent dosing, high efficacy, and high degree of safety.”

Alice B. Gottlieb, MD, PhD

IL-23 blockers have emerged as effective and well-tolerated options for the treatment of moderate to severe plaque psoriasis. Their advantages are infrequent dosing, high efficacy, and high degree of safety. Studies of IL-23 blockers in psoriatic arthritis have evaluated all of the domains of psoriatic arthritis, and they have shown positive results. Guselkumab is currently the only selective IL-23 blocker that is US Food and Drug Administration approved for psoriatic arthritis, and it is effective at controlling signs and symptoms and improving quality of life. The agent also has some positive data for use in patients with axial psoriatic arthritis. Studies assessing IL-23 blockers for the inhibition of radiographic progression in psoriatic arthritis are in progress.

It is important that clinicians who treat psoriasis determine whether the patient has psoriatic arthritis. It is not true that only patients with moderate to severe psoriasis develop psoriatic arthritis; in fact, those with psoriasis with very little skin involvement can develop psoriatic arthritis. I recently saw a patient with lesions on his penis that went undiagnosed for 20 years, as well as tips on his nails. At his first visit, I asked him if he had symptoms of psoriatic arthritis, and he said “no.” But during his follow-up visit, he told me, “You’re right. I’ve had plantar fasciitis.” This patient had psoriatic arthritis with minimal skin disease. So, if you do not ask, you may not get the information that you need from the patient.

The safety profiles of IL-23 blockers are good. Most of the serious adverse events reported in clinical trials, including serious infection, major adverse cardiovascular events, malignancy, and death, are in line with the expected proportions observed in the general population of patients with moderate to severe psoriasis. It is rare to see a reduction in white blood cell counts or to have liver function test elevations when these agents are used as monotherapy in patients with psoriasis. The risk of these 2 adverse events might be higher in those with psoriatic arthritis.

References

Baeten D, Østergaard M, Wei JC-C, et al. Risankizumab, an IL-23 inhibitor, for ankylosing spondylitis: results of a randomised, double-blind, placebo-controlled, proof-of-concept, dose-finding phase 2 study. Ann Rheum Dis. 2018;77(9):1295-1302. doi:10.1136/annrheumdis-2018-213328

Blair HA. Risankizumab: a review in moderate to severe plaque psoriasis. Drugs. 2020;80(12):1235-1245. doi:10.1007/s40265-020-01357-1

Brownstone ND, Hong J, Mosca M, et al. Biologic treatments of psoriasis: an update for the clinician. Biologics. 2021;15:39-51. doi:10.2147/BTT.S252578

Deodhar A, Helliwell PS, Boehncke W-H, et al; DISCOVER-1 Study Group. Guselkumab in patients with active psoriatic arthritis who were biologic-naive or had previously received TNFα inhibitor treatment (DISCOVER-1): a double-blind, randomised, placebo-controlled phase 3 trial [published correction appears in Lancet. 2020;395(10230):1114]. Lancet. 2020;395(10230):1115-1125. doi:10.1016/S0140-6736(20)30265-8

Ghoreschi K, Balato A, Enerbäck C, Sabat R. Therapeutics targeting the IL-23 and IL-17 pathway in psoriasis. Lancet. 2021;397(10275):754-766. doi:10.1016/S0140-6736(21)00184-7

Light JG, Su JJ, Feldman SR. Clinical utility of guselkumab in the treatment of moderate-to-severe plaque psoriasis. Clin Cosmet Investig Dermatol. 2021;14:55-63. doi:10.2147/CCID.S235242

Mease PJ, Rahman P, Gottlieb AB, et al; DISCOVER-2 Study Group. Guselkumab in biologic-naive patients with active psoriatic arthritis (DISCOVER-2): a double-blind, randomised, placebo-controlled phase 3 trial [published correction appears in Lancet. 2020;395(10230):1114]. Lancet. 2020;395(10230):1126-1136. doi:10.1016/S0140-6736(20)30263-4

Näslund-Koch C, Zachariae C, Skov L. Tildrakizumab: an evidence-based review of its use in the treatment of moderate-to-severe chronic plaque psoriasis. Ther Clin Risk Manag. 2020;16:903-916. doi:10.2147/TCRM.S227880

Salimi S, Yamauchi PS, Thakur R, et al. Interleukin 23p19 inhibitors in chronic plaque psoriasis with focus on mirikizumab: a narrative review. Dermatol Ther. 2020;33(4):e13800. doi:10.1111/dth.13800

Yang K, Oak ASW, Elewski BE. Use of IL-23 inhibitors for the treatment of plaque psoriasis and psoriatic arthritis: a comprehensive review. Am J Clin Dermatol. 2021;22(2):173-192. doi:10.1007/s40257-020-00578-0

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