COMMENTARY

New Psoriasis Treatments: A Primer

Jeffrey Liu; April W. Armstrong, MD, MPH

Disclosures

August 17, 2021

Oral Systemic Therapies — An Unmet Need

Despite the various novel systemic treatment options available for plaque psoriasis, there is still a need for additional oral therapies. Although older-generation oral agents such as methotrexate, retinoids, and cyclosporine can effectively treat plaque psoriasis, these drugs are associated with serious reactions and health risks and carry black box warnings. Currently, apremilast, a phosphodiesterase-4 (PDE-4) inhibitor, is the only oral nonbiologic medication in its class approved by the US Food and Drug Administration for moderate to severe plaque psoriasis. However, clinical trial data show tyrosine kinase-2 (TYK2) inhibitors, such as deucravacitinib, to be a promising therapeutic option in the treatment of plaque psoriasis.

Deucravacitinib is a novel, selective, oral TYK2 inhibitor that has shown robust efficacy and good tolerability and safety in patients with moderate to severe plaque psoriasis. By selectively targeting TYK2, deucravacitinib inhibits the effects of IL-12, IL-23, and interferon alfa and beta — the key cytokines that drive psoriasis. Two randomized, double-blind global phase 3 studies (POETYK PSO-1 and POETYK PSO-2) assessed the efficacy and safety of deucravacitinib 6 mg once daily compared with placebo and apremilast 30 mg twice daily in patients with moderate to severe plaque psoriasis. At week 16, among patients randomized to receive deucravacitinib, about 54% (POETYK PSO-1) and just over 50% (POETYK PSO-2) achieved static Physician Global Assessment scores of 0 (clear) or 1 (almost clear). These response rates were significantly higher than the little more than 7% (POETYK PSO-1) and almost 9% (POETYK PSO-2) observed in the placebo groups, and the little more than 32% (POETYK PSO-1) and just over 34% (POETYK PSO-2) in the apremilast groups. Also, at week 16, nearly 59% (POETYK PSO-1) and approximately 54% (POETYK PSO-2) of patients in the deucravacitinib group achieved PASI 75 responses compared with almost 13% (POETYK PSO-1) and just over 9% (POETYK PSO-2) of patients in the placebo group, and a little more than 35% (POETYK PSO-1) and around 40% (POETYK PSO-2) in the apremilast group. Furthermore, deucravacitinib responses increased beyond week 16 and were also superior to apremilast at week 24. Overall, deucravacitinib was well tolerated. There was a low rate of localized herpes zoster (0.93 events per 100 patient-years) in patients receiving deucravacitinib, with no patients needing discontinuation of treatment over 52 weeks.

In addition to deucravacitinib, other Janus kinase (JAK) inhibitors have been investigated for the treatment of plaque psoriasis. Early-phase studies demonstrated proof of concept with baricitinib (JAK1 and JAK2 inhibitor) and brepocitinib (TYK2 and JAK1 inhibitor).

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