Potential Role of Leptin in JAK2 Inhibitor-Associated Weight Gain: A Monocentric Retrospective Study

• DOI: 10.1093/ced/llaf144
• Publication Date: 2025-03-31T21:19:30Z
• Authors: Luciano Ibba; Luigi Gargiulo; Matteo Bianco; Sara Di Giulio; Ruggero Cascio In...; Angela Alfano; Carlo A Vignoli; Mario Valenti; Paola Facheris; Chiara Perugini; Alessandra Narcisi; Antonio Costanzo

Abstract Janus kinase (JAK) inhibitors are widely used for treating atopic dermatitis (AD) and alopecia areata (AA). Weight gain is an emergent adverse event associated with JAK inhibitors, particularly those acting on the JAK2 pathway. We conducted a retrospective monocentric 2-cohort study, including 226 patients, to evaluate the prevalence of weight gain in patients with AD and AA who were treated with JAK inhibitors for at least one year. We included 142 patients in the JAK1/2 cohort (receiving upadacitinib 30 mg or baricitinib 4 mg) and 84 in the JAK1 cohort (receiving upadacitinib 15 mg or abrocitinib 100 mg). The JAK1/2 cohort showed an additional weight gain throughout the study period (at week 52: β=1.84, 95% C.I. 1.45-2.23, p<0.001). In conclusion, patients receiving JAK1/2 inhibitors for AD or AA are at a greater risk of weight gain than those treated with JAK1 inhibitors, likely due to impaired leptin signaling.