Upadacitinib for the Management of Atopic Dermatitis in Patients Aged ≥60 Years: A Long-Term Multicenter Real-World Study

Background: Atopic dermatitis (AD) in the elderly is increasing worldwide and presents therapeutic challenges due to age-related comorbidities that often contraindicate systemic therapies. Although oral Janus kinase (JAK) inhibitors show efficacy in moderate-to-severe AD, older adult patients are underrepresented in clinical trials, and regulators recommend caution in this population. Materials and Methods: We conducted a multicenter, retrospective, observational study at 15 Italian university hospitals, including patients with moderate-to-severe AD aged ≥60 years treated with upadacitinib 15 or 30 mg once daily, to evaluate the real-world effectiveness and safety of this selective JAK1 inhibitor at weeks 16, 32, 52, and 104. Results: Seventy-two patients were included (mean age 65.9 ± 6.4 years); 48/72 (66.7%) of patients showed a classical flexural phenotype; 34/72 (47.2%) presented with head-and-neck involvement. Upadacitinib led to marked and sustained improvement in both clinician-and-patient-reported outcomes, with mean Eczema Area and Severity Index decreasing from 23.9 ± 9.2 at baseline to 1.5 ± 3.0 at week 52 and 0.9 ± 2.5 at week 104. Mean itch-Numeric Rating Scales (NRS) decreased from 8.2 ± 2.0 at baseline to 1.0 ± 1.9 at week 52 and 1.0 ± 2.4 at week 104, with concomitant amelioration in sleep-NRS (6.5 ± 3.1 to 0.5 ± 1.6 and 0.3 ± 1.3) and Dermatology Life Quality Index (16.8 ± 6.9 to 1.6 ± 4.2 and 1.0 ± 3.2). Adverse events occurred in 37/72 (51,4%) patients and included dyslipidemia in 22/72 (30.6%) patients, creatine phosphokinase elevation in 15/72 (20.8%), and blood count abnormalities in 13/72 (18.1%); they were mostly mild and manageable. Overall, 16/72 patients (22.2%) discontinued treatment, including 11/72 (15.3%) due to AEs. Conclusions: In our multicenter real-world cohort of patients aged ≥60 years, upadacitinib demonstrated rapid, sustained efficacy and an overall favorable safety profile through 104 weeks, supporting its long-term use in clinical practice with appropriate monitoring.