Moving beyond the Janus kinase signaling kinases in the pathogenesis and treatment of psoriasis and psoriatic arthritis

Abstract

Psoriatic disease encompasses psoriasis and psoriatic arthritis. It is a chronic, progressive condition and leads to irreversible joint destruction. Conventional treatments used are disease-modifying antirheumatic drugs and biologics. Janus kinase (JAK) signal transducers and activators of transcription (STAT) cell signaling protein inhibitors have shown promising results in psoriatic disease. However, JAK inhibitors have been associated with some concerning safety issues, such as cardiac risks, venous thrombotic episodes, malignancy, and infection. There are other developing molecules beyond JAK inhibitors, such as tyrosine kinase 2 (TYK2) inhibitors, RAR-related orphan receptor gamma (RORγ) inhibitors, mammalian target of rapamycin inhibitors, nerve growth factor inhibitors, and STAT kinase inhibitors. In this narrative review, we have discussed such molecular targets beyond JAK inhibitors to examine their role in the treatment of psoriatic disease. This review discusses the potential of these new options, particularly TYK2 inhibitors, which is already Food and Drug Administration approved for psoriasis. These advancements offer promising options for the management of psoriatic disease.