Interleukin-31 targeting and other novel drugs in itch

Chronic pruritus is a debilitating symptom of several inflammatory skin conditions, presenting severe quality-of-life decreasing effects and major clinical challenges in terms of disease management. In the past decade, novel biological therapies have offered increasingly effective targeted interventions for the treatment of chronic pruritus, in which traditional approaches were often lacking or presented suboptimal safety profiles. However, recent advancements in the molecular characterization of sensory neuronal subsets helped to shed light on specific mechanisms of pruriception and thus have furthered our understanding of the peripheral nervous system and disease-relevant neuroimmune crosstalk. These developments have highlighted the targeting of interleukin-31, a major pruritus-associated cytokine, as a highly promising therapeutic target for chronic pruritus in inflammatory skin conditions. In this review, we therefore provide a focused overview of inflammatory conditions in which pruritus represents the major burden, the fundamental immune pathways, and sensory circuits involved, alongside the efficacies and safety profiles of novel therapies addressing chronic pruritus.