Despite advances in the treatment of
psoriasis, 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 intracellular signalling of
cytokines of numerous cellular processes, important in both normal and pathological states of immune-mediated inflammatory diseases. Particularly in
psoriasis, where the
interleukin (IL)-23/IL-17 axis is currently considered the crucial pathogenic pathway, blocking the JAK-STAT pathway with small molecules would be expected to be clinically effective. However, relative non-specificity and low therapeutic index of the available
JAK inhibitors have delayed their integration into the therapeutic armamentarium of
psoriasis. Current research appears to be focused on
Tyrosine kinase 2 (TYK2), the first described member of the JAK family. Data from the Phase II trial of BMS-986165-a selective TYK2 inhibitor-in
psoriasis have been published and clinical results are encouraging, with a large Phase III programme ongoing. Further, the selective TYK2 inhibitor
PF-06826647 is being tested in moderate-to-severe
psoriasis in a Phase II clinical trial. Brepocitinib, a potent TYK2/JAK1 inhibitor, is also being evaluated, as both oral and topical treatment. Results of studies with TYK2 inhibitors will be important in assessing the clinical efficacy and safety of these drugs and their place in the therapeutic armamentarium of
psoriasis. This article reviews current data on the impact of
JAK inhibitors in the treatment of adult patients with moderate-to-severe
psoriasis.