LAUSR

Background. Blocking agent for immune cytokine pathways is a novel treatment for atopic dermatitis (AD). Janus kinase (JAK) family is one of the cytoplasmic tyrosine kinases that mediate a variety of cytokines. Eight randomized controlled trials (RCTs) of JAK1 inhibitors (upadacitinib and abrocitinib) in AD have been published in the past three years. Objective. To evaluate the efficacy and safety of JAK1 inhibitors and compare upadacitinib with abrocitinib for the treatment of moderate-to-severe AD. Methods. Two independent reviewers searched Medline, Embase, Web of Science, and Cochrane databases updated on Apr 11th, 2023. We included data from phase two and three RCTs. Primary outcomes included the proportion of Investigator’s Global Assessment (IGA) responders and Eczema Area and Severity Index-75 (EASI-75) responders. Results. In all, eight RCTs were included in our study with 4634 moderate-to-severe AD patients. Both JAK1 inhibitors showed apparent therapeutic effects, but the 200 mg abrocitinib group demonstrated less efficacy than the 30 mg upadacitinib group in IGA responders (end of treatment) and EASI-75 responders (after 2 weeks of treatment). However, both JAK1 inhibitor groups demonstrated significantly higher risks of acne (9.0%) and headache (6.3%). Besides, upadacitinib showed significantly higher risks of upper respiratory tract infection (7.6%) and nasopharyngitis (9.7%), and abrocitinib showed significantly higher risks of nausea (9.6%). Conclusion. JAK1 inhibitors demonstrate promising efficacy in AD with rapid response and dose-dependent response and significantly higher risks of acne and headache. Based on existing data, oral 30 mg upadacitinib QD has better outcome than oral 200 mg abrocitinib QD and is a recommended dosage regimen for moderate-to-severe AD patients. Oral 15 mg upadacitinib QD might be an alternative dosage regimen in case of treatment-emergent adverse events.