Comparison of Long-Term Effectiveness and Safety of Upadacitinib for Atopic Dermatitis Between Dupilumab-Exposed and Dupilumab-Naïve Patients.

ABSTRACT

BACKGROUND AND OBJECTIVES: Upadacitinib is an oral selective Janus kinase-1 inhibitor approved for the treatment of moderate-to-severe atopic dermatitis (AD) in patients [Formula see text] 12 years of age. In real life, upadacitinib currently represents a valid therapeutic option for patients failing available systemic therapies, in particular patients who discontinued dupilumab because of lack of efficacy or occurrence of adverse events. The objectives of the present study were to compare the effectiveness and safety of upadacitinib in patients affected by AD who had previously failed dupilumab therapy versus biologic naïve patients. METHODS: A retrospective, multi-centre, observational, real-life study was conducted in four Italian dermatological referral centres (Milan, Perugia, Naples and Vicenza). Baseline characteristics included age, sex, AD history and severity, prior treatments, comorbidities and concomitant therapies. AD severity was assessed at baseline and at week 4 (W4), W16, W24 and W52, using Eczema Area Severity Index (EASI), Dermatology Life Quality Index (DLQI) and Pruritus Numerical Rating Scale (P-NRS) scores. Full blood count, hepatic and renal function, lipid panel, and muscle enzymes [lactate dehydrogenase (LDH) and creatine phosphokinase (CPK)] were assessed at baseline and at each follow-up visit. RESULTS: A total of 113 patients (72 males, 63.7%; mean age 37.22 ± 16.8 years) were included in the analysis, all patients were in treatment and underwent follow-up period until W16, whilst 91 (80.5%) and 75 (66.4%) patients were in treatment and in follow-up period until W24 and W52, respectively. Mean EASI score significantly changed from 24.30 ± 10.27 to 1.28 ± 4.34, 0.74 ± 2.31 and 0.25 ± 1.34 at W16, W24 and W52, respectively (p < 0.0001). Specifically, at W16 the percentage of patients achieving EASI-75, EASI-90 and EASI-100 was 85.21, 76.35 and 66.11%, respectively. At W24, EASI-75, EASI-90 and EASI-100 were reached by 88.54, 85.42, and 78.37% of patients, respectively. Finally, 90.1% of patients achieved EASI-75, 88.3% achieved EASI-90 and 83.0% achieved EASI-100 at W52. CONCLUSIONS: This study confirmed the clinical effectiveness of upadacitinib treatment in adult patients in a real-world setting with moderate-to-severe AD who had discontinued dupilumab due to poor effectiveness or adverse events and who were biologic naïve; therefore, previous treatments do not seem to affect the response to upadacitinib treatment.