Deucravacitinib for the Treatment of Psoriatic Disease

Abstract

Psoriasis is an immune-mediated disease, with the interleukin (IL)-23/IL-17 axis currently considered its main pathogenic pathway. Tyrosine kinase 2 (TYK2) is responsible for mediating immune signalling of IL-12, IL-23 and type I interferons, without interfering with other critical systemic functions as other JAK proteins do. This article aims to review the current knowledge on deucravacitinib, a new oral drug that selectively inhibits TYK2, granting it a low risk of off-target effects. After good efficacy and safety results in a phase II, placebo-controlled trial, two phase III, 52-week trials evaluated deucravacitinib 6 mg against placebo and apremilast-an active comparator. POETYK PSO-1 and PSO-2 involved 1688 patients with moderate-to-severe psoriasis. After 16 weeks, in both studies, over 50% of patients treated with deucravacitinib reached PASI75, which was significantly superior to placebo and apremilast. In POETYK PSO-1, these results improved until week 24 and were maintained through week 52, with over 65% of patients achieving PASI75 at this point. A reduction in signs and symptoms was also reported by patients, with greater impact on itch. Deucravacitinib was well tolerated and safe. There were no reports of serious infections, thromboembolic events, or laboratory abnormalities, which are a concern among other JAK inhibitors. Persistent efficacy and consistent safety profiles were reported for up to 2 years. Despite advances in the treatment of psoriasis, namely among biologic agents, an oral, effective and safe new drug can bring several advantages to prescribers and patients. Further investigation is required to understand where to place deucravacitinib among current psoriasis treatment options.

Fig. 1

Schematic representation of Janus Kinase Signal Transducer and Activator of Transcription (JAK/STAT) pathway and respective activating cytokines. Circulating cytokines couple to their receptors in the cell membrane. That connection triggers a conformational change of the receptor, which recruits a combination of autophosphorylated JAKs. Different receptors associate with different JAKs, each of them associated with specific biologic functions. JAKs create conditions to phosphorylate STAT proteins, causing their dimerization, which enables them to move into the cell nucleus and modulate gene expression. EPO erythropoietin, G-CSF granulocyte colony-stimulating factor, GH growth hormone, GM-CSF granulocyte–macrophage colony-stimulating factor, IL interleukin, IFN interferon, TPO thrombopoietin, TYK tyrosine kinase