Not just another klass (JAK) of inhibitors for allergies

Abstract

In the past decade, Janus kinase (JAK) inhibitors have emerged as a new therapeutic class for treating allergies. Based on new insights from genetic studies and increased knowledge regarding pathophysiology, JAK1 and downstream STAT6 have been characterized as the main therapeutic target pathway in allergies. As a consequence, oral JAK1/2 (baricitinib) and specific JAK1 inhibitors (abrocitinib, upaticinib) have received approval in atopic dermatitis and a dual inhibitor targeting JAKs and SYK, another important tyrosine kinase implicated in allergies, is in development (gusacitinib). Moreover, JAK inhibitors have demonstrated their efficacy in animal models for food allergies and in humans for asthma. In atopic dermatitis, JAK inhibitors are effective as early as 1-week post-administration in reducing eczema disease activity, pruritus, skin pain, and by improving sleep and quality of life. In 2023, a warning label was placed on JAK inhibitors based on an excess risk for serious heart-related events and cancer reported in rheumatoid arthritis (RA) patients undergoing JAK inhibitor treatment. More studies are necessary to evaluate the safety and efficacy of this approach applied to allergies with regards to usage of glucocorticoids and distinct risk factors.