Upadacitinib for Refractory Paediatric Atopic Dermatitis: A Real-World Study on Effectiveness and Safety in Dupilumab Nonresponders

To evaluate the efficacy and safety of upadacitinib use in pediatric patients with atopic dermatitis (AD) refractory to conventional corticosteroid therapy and dupilumab in a real-world study.Pediatric patients aged 6 to 14 years with AD refractory to dupilumab treated at Beijing Children’s Hospital. Inclusion criteria included treatment failure with conventional topical corticosteroid treatment and nonresponsiveness to dupilumab as defined by a minimum 16-week trial period with less than a 50% reduction in the Eczema Area and Severity Index (EASI).Prospective, open-label trial of upadacitinib 15-mg daily treatment over a 16-week period. Patients’ response to therapy was conducted at follow-up visits at weeks 4, 8, and 16. Treatment efficacy was measured using the EASI, Numerical Rating Scale (NRS), Investigator’s Global Assessment (IGA), and Children’s Dermatology Life Quality Index (CDLQI).Twelve children were enrolled. Significant improvements (P < .01) in median scores were observed in the EASI, NRS, IGA, and CLDQI scoring tools. At 16 weeks, 50.3% of patients achieved a 75% reduction in EASI scores, 91.7% of patients had at least a 4-point reduction in NRS, and 66.7% of patients concluded the study with an IGA of 0/1. The most common adverse reaction was acne (33.3%). Twenty-five percent of patients had an infection during the observation period (upper respiratory infection, n = 2; acute otitis media, n = 1). Several laboratory abnormalities were noted, including elevations in gamma-glutamyl transferase, alanine aminotransferase, direct bilirubin, creatine kinase–myocardial band, and anemia.The use of upadacitinib in pediatric patients with refractory AD led to significant improvements across several AD scoring tools. It is a well-tolerated medication, but it requires monitoring for infection, anemia, and biochemical laboratory abnormalities.Upadacitinib targets the Janus Kinase/Signal Transducers and Activators of Transcription pathway, and it exerts its effects downstream of several cytokines (compared with dupilumab, which selectively targets the interleukin 4 [IL-4]/IL-13 pathway). The broader scope of this mechanism of action may lead to greater efficacy in patients unresponsive to conventional therapy and dupilumab. The study demonstrated promising improvements in AD disease burden in difficult-to-treat pediatric patients younger than the approved 12-year-and-older indication, but it was limited by sample size and duration of follow-up, which should be addressed in larger studies.