Role of Janus Kinase Inhibitors in Therapy of Psoriasis

Abstract

Janus kinases inhibitors are molecules that target Janus kinases—signal transducers and activators of transcription (JAK/STAT). They inhibit this intracellular signal pathway, blocking the gene transcription of crucial proinflammatory cytokines that play a central role in the pathogenesis of many inflammatory and autoimmune diseases, including psoriasis. This process reduces psoriatic inflammation. The JAK inhibitors are divided into two generations. The first generation of JAK inhibitors blocks two or more different Janus kinases. The second generation is more specified and blocks only one type of Janus kinase and has less side effects than the first generation. Tofacitinib, ruxolitinib and baricitinib belong to first generation JAK inhibitors and decernotinib and filgotinib belong to second group. This narrative review summarizes the role of Janus kinase inhibitors in the therapy of psoriasis. Oral JAK inhibitors show promise for efficacy and safety in the treatment of psoriasis. Studies to date do not indicate that JAK inhibitors are superior to recent biologic drugs in terms of efficacy. However, JAK inhibitors, due to their lack of increased incidence of side effects compared to other biologic drugs, can be included in the psoriasis treatment algorithm because they are orally taken. Nevertheless, further studies are needed to evaluate long-term treatment effects with these drugs.

Concurrent bullous pemphigoid and plaque psoriasis successfully treated with Janus kinase inhibitor Baricitinib

“…The favorable response to Baricitinib in this patient appears to support our hypothesis. In addition, clinical trials of Baricitinib have shown encouraging effects without serious side effects in treatment of various other autoimmune skin diseases including psoriasis, 14,15 which is in line with the results of our case. Other benefits of Baricitinib include its easy oral administration and lower cost compared to other intravenous/ subcutaneous agents which are invasive and more expensive.…”

The Cytokine Mediated Molecular Pathophysiology of Psoriasis and Its Clinical Implications

“…Currently, there are no FDA-approved JAK inhibitors in the treatment of psoriasis, however, oral tofacitinib is approved for psoriatic arthritis. Oral tofacitinib, is a JAK1 and JAK2 inhibitor and is the most studied oral JAK inhibitor in moderate to severe plaque psoriasis ( Table 6 ) [ 108 ]. Deucravacitinib, formerly known as BMS986165, is an oral selective TYK2 inhibitor.…”

“…JAK inhibitors are also an emerging class of small molecule inhibitors, and oral tofacitinib is the most studied oral JAK inhibitor in psoriasis [ 108 , 111 , 112 ]. Although JAK inhibitors present a new small molecule inhibitor with efficacy in psoriasis, it is associated with numerous black box warnings, and careful consideration must be used when opting for these medications [ 55 , 113 ].…”

Unmet Medical Needs in Chronic, Non-communicable Inflammatory Skin Diseases

“…In late stages of clinical development is the TYK2 inhibitor deucravacitinib, which in clinical trials offers quite convincing clinical effects with a good safety profile. The background for the latter development is the recognition that many mediators, for example type I interferons or IL-23, mediate their inflammatory signals via Janus kinases (JAK, to which TYK2 also belongs) ( 85 , 86 ). Thus, by blocking these signaling molecules, an (indirect) inhibition of inflammatory mechanisms can be achieved.…”