Real-World Evidence of Effectiveness and Safety of Abrocitinib, Baricitinib and Upadacitinib in Atopic Dermatitis: A Systematic Review and Meta-Analysis.

backgroundOral Janus kinase inhibitors (JAKi) have proven effective in the treatment of atopic dermatitis (AD) in multiple clinical trials, providing rapid response, deep efficacy when given at the highest formulated dose, and in the case of abrocitinib and upadacitinib, superiority to biologics treatments in the first 4-16 weeks. However, it is unclear how this translates to real-world efficacy and safety.

objectivesTo assess the real-world effectiveness and safety of abrocitinib, baricitinib and upadacitinib in the treatment of AD.

methodsPubMed and EMBASE were systematically searched from inception until 3 January 2025 for observational studies investigating effectiveness and safety of abrocitinib, baricitinib and upadacitinib for the treatment of AD. The primary outcomes were the proportion of patients achieving a ≥ 75% improvement in the Eczema Area and Severity Index (EASI-75) following treatment with abrocitinib, baricitinib or upadacitinib after 12 and 16 weeks. Secondary outcomes included the proportion of patients achieving EASI-50, EASI-90 and the proportion of patients experiencing adverse events (AE). Tertiary outcomes included the Dermatology Life Quality Index (DLQI) and the Peak-Pruritus Numerical rating scale (PP-NRS).

resultsA total of 63 studies including 517 patients treated with abrocitinib (50 mg [0.2%], 100 mg [50.9%], 200 mg [34.2%], mixed/unknown [14.7%]), 574 with baricitinib (2 mg [14.8%], 4 mg [71.9%], mixed/unknown [13.3%]) and 2779 with upadacitinib were included (15 mg [46.6%], 30 mg [33.3%], mixed/unknown [20.0%]). Most studies reported outcomes for doses combined. Across all doses, the proportion of patients achieving EASI-75 and -90 was 75% and 38% for abrocitinib, 51% and 24% for baricitinib and 83% and 55% for upadacitinib after 16 weeks, respectively. Acne and herpes simplex virus (HSV) were frequently reported across all doses of abrocitinib (21%, 2%), baricitinib (8%, 6%) and upadacitinib (15%, 6%), but patients treated with 100 mg abrocitinib and 30 mg upadacitinib reported the highest prevalence of acne and HSV, respectively. Few studies reported serious AEs across all treatments and doses.

conclusionsData from real-world studies of JAKis in AD show effectiveness and safety similar to clinical trials using the highest treatment doses. It is important to be aware of HSV and acne risk as these AEs are the most common reasons for discontinuation. Interpretation of results was complicated by the lack of studies reporting dosage information.