Oral small molecules: new therapeutic targets in psoriasis

Abstract

Psoriasis is a chronic immune-mediated skin disease frequently associated with different comorbidities, among which psoriatic arthritis stands out, with a high impact on the quality of life of patients. We have an important therapeutic arsenal that includes topical agents, phototherapy and systemic drugs. In recent years, biological therapy has brought about a true revolution in the treatment of moderate to severe psoriasis, due to its great efficacy and safety. However, it has some limitations such as its exclusively parenteral administration, its high cost and the lack of efficacy and tolerance in some cases. Therefore, based on a better knowledge of the pathophysiology of psoriasis, new therapeutic options have emerged: the small molecules. They represent an enrichment for the clinician in the therapeutic management of psoriasis. Some of those have approved indication and others under investigation. The objective of this review is to analyze the efficacy and safety data of these molecules that include phosphodiesterase inhibitors (apremilast), Janus kinase inhibitors (tofacitinib, baricitinib), selective tyrosine kinase 2 inhibitors (deucravacitinib), agonists G protein-associated A3 adenosine receptor (piclidenoson), orphan T-gamma receptor inverse agonists (vimirogant), and sphingosine-1-phosphate receptor antagonists (ponesimod). In addition, new molecular targets are discussed. In short, the frontline of new systemic treatment for psoriasis.