Janus kinase inhibitors are novel therapeutics for treating atopic dermatitis, and can be administered both orally or topically. This meta-analysis focuses on the safety and efficacy of oral janus kinase inhibitors.
Atopic dermatitis (AD) is one of the most common inflammatory skin diseases, and its pathogenesis involves skin barrier disruption and immune activation of T-helper 2, T-helper 22, and varying amounts of T-helper 1 and T-helper 17 cells, depending on the patient subtype. AD is clinically heterogeneous, and more efficacious treatments are needed that can target multiple immune axes. Janus kinase (JAK) inhibitors are new therapies that mainly block various AD-related proinflammatory cytokines across different immune pathways.
Two oral JAK inhibitors: abrocitinib and upadacitinib, recently gained UDA approval, and many others are currently being investigated in clinical trials. Although these oral systemic treatments have provided very good skin clearance, they are associated with various health concerns. This review, published in Annals of Allergy, Asthma, and Immunology, summarizes the current literature on the safety and efficacy of oral JAK inhibitors.
AD Challenges and Meta-Analysis Techniques to Determine Efficacy and Safety
AD presents with distinct endotypes based on age, filaggrin status, ethnicity, disease chronicity, and immunoglobulin E levels. T-helper 2 skewing is common to all subtypes of AD, but variably activates other immune axes in different subtypes. AD pathogenesis is similarly varied, and involves genetics, immune aberrations, skin barrier dysfunction, and environmental factors, although increased activated T-cell infiltration is common in all forms.
For this study, the literature on JAK inhibitors was reviewed through July 2022. Data on the efficacy and safety of a number of systemic oral JAK inhibitors are described, including, upadacitinib, an oral selective JAK1 inhibitor that has been approved by the FDA for rheumatoid arthritis, as well as for AD in 2022; baracitinib, a first-generation JAK1/2 selective inhibitor that has not been approved for AD in the U.S., but has been approved in Europe; and tofacitinib, a pan-JAK inhibitor that is mainly selective for JAK1 and JAK2, although it retains some efficacy for JAK2 and TYK2. Oral tofacitinib has been FDA-approved for various conditions, but has yet to be approved for treating AD.
JAK Inhibitors: The Promising Future of AD Treatment
This meta-analysis shows that JAK inhibitors are largely efficacious in patients with moderate-to-severe AD. Some patients with AD who received treatment using upadacitinib and abrocitinib reached EASI-100, which has not previously been reported in patients with AD, regardless of the treatment they received. EASI-90 responses with upadacitinib and abrocitinib occurred at sufficiently high rates, as well, showing that these treatment options are a very promising way to treat AD more comprehensively than has been possible, so far. However, additional long-term clinical trials are needed in order to characterize the safety profile of these treatments.
Source:
Mikhaylov, D., Ungar, B., Renert-Yuval, Y., & Guttman-Yassky, E. (2023). Oral Janus kinase inhibitors for atopic dermatitis. Annals of Allergy, Asthma, and Immunology. https://doi.org/10.1016/j.anai.2023.01.020
