Effectiveness and safety of upadacitinib retreatment after withdrawal in moderate-to-severe atopic dermatitis: a retrospective study

Background Upadacitinib, a Janus kinase 1 (JAK1) inhibitor, is effective for moderate-to-severe atopic dermatitis (AD). Upadacitinib treatment may be discontinued in some patients; however, the effectiveness and safety of retreatment after its withdrawal have not been examined in detail in real-world practice.Objectives To evaluate the effectiveness and safety of upadacitinib retreatment after withdrawal in real-world clinical practice for Japanese patients with AD.Methods This retrospective study included 62 Japanese patients with moderate-to-severe AD treated with upadacitinib 15 mg (n = 38) or 30 mg (n = 24). Effectiveness was assessed using the Eczema Area and Severity Index (EASI) and Peak Pruritus Numerical Rating Scale (PP-NRS) before treatment (baseline), at timepoints of discontinuation, at retreatment, and at week 12 after retreatment with upadacitinib. Safety was evaluated through the incidence of treatment-emergent adverse events (TEAEs).Results EASI and PP-NRS scores significantly decreased at week 12 after upadacitinib retreatment compared with baseline in both the 15-mg and 30-mg groups (P = 0.01 for EASI and PP-NRS in both groups). At week 12 after retreatment, achievement rates of at least a 75%, 90% or 100% reduction in EASI from baseline (EASI 75, EASI 90 or EASI 100, respectively) were 84%, 57% and 19% in the 15-mg group, and 87%, 57% and 17% in the 30-mg group, respectively. TEAEs were mild or moderate, and no serious AEs or deaths were reported.Conclusions Retreatment with upadacitinib after withdrawal effectively improved clinical signs and pruritus in patients with AD, with a manageable safety profile, supporting its use for long-term management of AD. Our study demonstrates that retreatment with upadacitinib after withdrawal effectively restores treatment responsiveness in patients with atopic dermatitis. Both 15-mg and 30-mg upadacitinib retreatments were associated with significant improvements in clinical signs and pruritus, with favourable safety profiles. These findings support the proposal that retreatment with upadacitinib may act as a useful treatment option for patients showing relapses of skin symptoms after drug withdrawal.