Abstract
Psoriasis and psoriatic arthritis (PsA), together known as psoriatic disease, are prevalent chronic inflammatory conditions affecting the skin, joints, or both and are associated with several comorbidities. Advances in understanding molecular and cellular pathways have identified tumor necrosis factor α (TNF-α), interleukin (IL) 17, 23 and 22 as major contributors to psoriasis pathogenesis and have led to the development of highly effective therapeutic agents targeting these cytokines.
However, there is an unmet need for effective and safe oral treatments. The Janus kinase / signal transducer and activator of transcription (JAK/STAT) pathway plays a significant role in the pathogenesis of these diseases.
Inhibition of the JAK/STAT pathway by tofacitinib and upadacitinib appears to be effective in psoriatic arthritis and resulted in approval for therapeutic use. Secondary outcomes from phase III trials point towards efficacy on psoriasis as well.
However, relative non-specificity and low therapeutic index of JAK inhibitors have delayed their integration into the therapeutic armamentarium of psoriasis. On the other hand, selective tyrosinkinase 2 (TYK2) inhibitors that can prevent IL-23/IL-17 axis signaling have raised significant expectations regarding oral treatment of moderate-to-severe psoriasis.