Real‐life efficacy and safety of upadacitinib in adolescents with moderate‐to‐severe atopic dermatitis unresponsive to dupilumab: A case series

Dear Editor, Upadacitinib, an oral Janus kinase 1 inhibitor, was recently approved by the European Medicines Agency for the treatment of moderatetosevere atopic dermatitis (AD) in patients aged ≥12 years and candidates for systemic treatment. Its efficacy and safety in the management of adult AD was reported by clinical trials, 6 and confirmed by reallife studies. 11 However, realworld experiences on adolescents are absent. Herein, we report a case series on four adolescent patients (three male, 75.0%; mean age: 16.25 ± 0.96 years, range 14– 17 years), affected by moderatetosevere AD undergoing treatment with upadacitinib for at least 16 weeks (W). Upadacitinib was administered at the dose of 15 mg once a day (QD). The effectiveness of upadacitinib was assessed evaluating the following scores at baseline, W4 and W16: Eczema Area Severity Index (EASI), children's Dermatology Life Quality Index (cDLQI), Pruritus Numerical Rating Scale (PNRS) and Sleep Numerical Rating Scale (SNRS). In order to assess safety, at baseline, W4 and W16 the following parameters were evaluated: full blood count, renal and hepatic function, muscle enzymes [lactate dehydrogenase and creatine phosphokinase (CPK)] and lipid panel. Furthermore, B and C hepatitis, and tubercular infections were ruled out before starting treatment. Statistical analysis using GraphPad Prism 4.0 (GraphPad Software Inc.) was carried out. Student's ttest was used to assess the statistical significance of the differences in values obtained at the different timepoints of treatment. p values <0.05 were considered to be statistically significant. The baseline demographic and clinical features of the patients are reported in Table 1. Three (75.0%) patients had developed AD before 1 year of age. Conjunctivitis was the most frequent atopic comorbidity (3; 75.0%), followed by rhinitis (2; 50.0%) and asthma (1; 25.0%). All the patients had received at least one systemic treatment for AD. In particular, they all had received dupilumab (mean treatment duration: 17.25 ± 1.26 months), discontinuing therapy for loss of efficacy (1; 25.0%), severe conjunctivitis (2; 50.0%) or red face (1; 25.0%). At baseline, all the patients showed the combination of flexural eczema and head and neck dermatitis; the mean values of EASI, cDLQI, PNRS and SNRS were 27.5 ± 1.29, 27.75 ± 2.22, 9.25 ± 0.96 and 9.0 ± 0.82, respectively. A statistically significant improvement of EASI was observed at W4 and W16 compared with baseline [W4: 9.75 ± 2.22, W16: 2.25 ± 1.70, p < 0.0001 for both]. At W16, all the patients achieved a 75% reduction of EASI value (EASI75) and two of them (50.0%) EASI90. A statistically significative reduction of cDLQI, PNRS and SNRS was also assessed at each timepoint [DLQI: W4 = 6.25 ± 2.75, W16 = 1.75 ± 1.71 (p < 0.0001 for both); PNRS: W4 = 1.50 ± 1.29, W16 = 0.75 ± 0.96 (p < 0.0001 for both); SNRS: W4 = 2.0 ± 1.15, W16 = 0.5 ± 0.58 (p < 0.0001 for both)] (Table 1). Regarding the safety, only one(25.0%) patient experienced not clinically relevant CPK increase. No serious adverse events (AEs) were reported. Upadacitinib showed promising results in the management of moderatetosevere AD. 11 Some clinical trials evaluated the efficacy and safety of upadacitinib in severe AD patients, including adolescents. 6 However, reallife data on adolescent patients are scant. To the best of our knowledge, our case series is the first realworld experience reporting the effectiveness and safety of upadacitinib in adolescent AD patients. Comparing our results with those obtained in clinical trials on AD adolescents undergoing treatment with 15 mg upadacitinib, we observed higher rates of EASI75 responses at W16. Indeed, in replicate studies Measure Up1 (n = 42 adolescents) and Measure Up2 (n = 33 adolescents), 71% and 67%, respectively, of adolescents assuming upadacitinib in monotherapy achieved EASI75. In our study this rate was 100%; this was also probably due to the concomitant use of medium potency topical corticosteroids in our patients in case of AD flare, as per good clinical practice. However, in phase 3 clinical trials AD Up (n = 39 adolescents) and Rising up (n = 10 adolescents, only Japanese), in which the application of mediumhigh potency corticosteroid was permitted, the rate of adolescent patients achieving EASI75 at W16 was 56% and 70.0%, respectively. Furthermore, in our experience 50.0% of patients achieved EAS90, compared to 40.0% in Rising Up study. Finally, one AE was observed in our patients, while in Rising Up study 27 AEs were registered among adolescent patients, one leading to the interruption of the treatment; however, in this trial a 24week analysis was considered. Even if limited, our experience suggests Received: 9 December 2022 | Accepted: 23 February 2023