Selective TYK2 Inhibition in the Treatment of Moderate to Severe Chronic Plaque Psoriasis

Melinda J. Gooderham, MSc, MD, FRCPC; H. Chih-ho Hong, MD, FRCPC; Ivan V. Litvinov, MD, PhD, FRCPC

Skin Therapy Letter. 2022;27(6):1-5.

Abstract and Introduction

Abstract

Moderate to severe chronic plaque psoriasis may be difficult to control using current therapies, which has led to development of a novel class of therapy, selective tyrosine kinase 2 (TYK2) inhibitors, to address this unmet need. Oral deucravacitinib is a first-in-class selective TYK2 inhibitor, which has shown efficacy in moderate to severe chronic plaque psoriasis from two phase III pivotal trials (POETYK PSO-1 and PSO-2), whereby response rates were significantly higher with deucravacitinib vs. placebo or apremilast for Psoriasis Area Severity Index (PASI) 75 and static Physician's Global Assessment (sPGA) 0/1. Deucravacitinib was generally well tolerated and safe compared to placebo and apremilast. Although deucravacitinib is a type of Janus kinase (JAK) inhibitor, it only blocks specific cytokine-driven responses, potentially reducing off-target effects more commonly associated with other JAK inhibitors on the market. Incidence rates of serious adverse events, such as serious infections, malignancies, thrombosis, cardiovascular events, creatinine kinase elevation, hematologic changes, and lipid profile abnormalities were absent or low.

Introduction

Psoriasis is a common, chronic, immune-mediated inflammatory disease, estimated to affect 1 million people in Canada.^[1,2] The most common type is chronic plaque psoriasis, which affects 90% of this patient population.^[1]

Moderate chronic plaque psoriasis is typically defined as involving ≥3–10% body surface area (BSA), with severe disease involving more than 10% BSA.^[3] When inadequately treated, this can cause severe psychosocial impact and impair patients' quality of life (QoL).^[3]

Currently, various oral systemic agents, biologic agents, and phototherapy have Health Canada-approved indications for management of moderate to severe chronic plaque psoriasis. Despite numerous treatment options, unmet needs still exist. An emerging class of therapy in development are selective tyrosine kinase 2 (TYK2) inhibitors, which may meet those needs. Oral deucravacitinib is a first-in-class selective TYK2 inhibitor, recently US FDA approved and currently under review by Health Canada. Other oral selective TYK2 inhibitors for treatment of moderate to severe plaque psoriasis in various stages of development include GLPG3667 and NDI-034858.^[4,5]

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Table 1. POETYK PSO-1 and PSO-2 efficacy results
Endpoint	POETYK PSO-1 (n=666) POETYK PSO-2 (n=1,020)					POETYK PSO-1 (n=666) POETYK PSO-2 (n=1,020)
Endpoint	Deucravacitinib 6 mg QD (n=332)	Apremilast 30 mg BID (n=168)	Placebo (n=166)	P value vs. apremilast	P value vs. placebo	Deucravacitinib 6 mg QD (n=511)	Apremilast 30 mg BID (n=254)	Placebo (n=255)	P value vs. apremilast	P value vs. placebo
PASI 75, %
Week 16	58.4%*	35.1%	12.7%*	<0.0001	<0º.0001	53.6%*	40.2%	9.4%*	0.0003	<0.0001
Week 24	69.3%	38.1%	-	<0.0001	-	59.3%	37.8%	-	<0.0001	-
sPGA 0/1, %
Week 16	53.6%*	32.1%	7.2%*	<0.0001	<0.0001	50.3%*	34.3%	8.6%*	<0.0001	<0.0001
Week 24	58.7%	31.0%	-	<0.0001	-	50.4%	29.5%	-	<0.0001	-
ss-PGA 0/1, %
Week 16	70.3%	39.1%	17.4%	<0.0001	<0.0001	60.3%	37.3%	17.3%	<0.0001	<0.0001
Week 24	72.2%	42.7%	-	<0.0001	-	59.7%	41.3%	-	0.0002	-
DLQI 0/1, %
Week 16	41.0%	28.6%	10.6%	0.0088	<0.0001	38.0%	-28.3	9.8%	<0.0001	<0.0001
Week 24	48.1%	24.2%	-	<0.0001	-	41.8%	-29.1	-	<0.0001	-
Change from baseline PSSD symptom score, adjusted mean
Week 16	-26.7	-17.8	-3.6	<0.0001	<0.0001	-28.3	-21.1	-4.7	<0.0001	<0.0001
Week 24	-31.9	-20.7	-	<0.0001	-	-29.1	-21.4	-	<0.0001	-

*Coprimary endpoints: response rates for PASI 75 and sPGA 0/1 with deucravacitinib vs. placebo at week 16.BID, twice daily; DLQI, Dermatology Life Quality Index; PASI 75, ≥75% reduction from baseline in Psoriasis Area and Severity Index; PSSD, Patient-reported symptoms and signs of psoriasis, evaluated using the Psoriasis Symptoms and Signs Diary; QD, once daily; SE, standard error; sPGA 0/1, static Physician's Global Assessment score of 0 or 1; ss-PGA, scalp-specific Physician's Global Assessment. Adapted from Armstrong AW, et al. 2022 and Armstrong A, et al. 2021.^15,16