The preclinical discovery and development of deucravacitinib for the treatment of psoriasis

IntroductionPsoriasis is a chronic inflammatory skin disease that most commonly presents as plaque psoriasis. The understanding of the pivotal pathogenetic role of the IL-23/IL-17 axis has dramatically changed the therapeutic approach to the disease. The identification of intracellular signaling pathways mediating IL-23 activity provided the rationale for targeting TYK2.Areas coveredThis review assesses the underlying rationale that led to development of deucravacitinib, a novel oral TYK2 inhibitor, as a therapeutic option for the treatment of moderate-to-severe psoriasis, primarily focusing on pre-clinical and early phase clinical studies.Expert opinionInnovative therapies used in patients with moderate-to-severe psoriasis include biologic agents and small molecules, which are associated with less adverse events than traditional systemic agents. Deucravacitinib, which selectively targets TYK2, has demonstrated to be effective in treating psoriasis, preserving a more favorable safety profile compared to other JAK inhibitors approved for the treatment of other immune diseases that block the ATP-binding site. Because of its oral administration, deucravacitinib represents an intriguing option in the therapeutic armamentarium of psoriasis, though the evaluation of long-term efficacy and safety is necessary to establish its place-in-therapy.

Automated summary

Psoriasis is a chronic inflammatory skin disease, with plaque psoriasis being the most common form. Understanding the role of the IL-23/IL-17 axis has led to a new approach in treating the disease. The development of deucravacitinib, an oral TYK2 inhibitor, as a therapeutic option for moderate-to-severe psoriasis is based on pre-clinical and early phase clinical studies.