Clinical Efficacy and Potential Biomarkers of Response to Upadacitinib Therapy in Patients with Severe Atopic Dermatitis and Comorbidities

Introduction. Atopic dermatitis (AD) is a chronic inflammatory skin disease. Its pathogenesis involves key roles of Th2-cell and type 2 innate lymphoid cell (ILC2) cytokines — IL-4, IL-13, and IL-31 — which activate JAK/STAT signaling pathways (primarily JAK1/STAT6). Despite the proven efficacy of JAK inhibitors, including upadacitinib, additional real-world clinical data are needed, especially in patients with refractory AD and comorbid conditions.

Aim — to evaluate the long-term efficacy, safety, and dynamics of potential biomarkers during upadacitinib therapy in patients with severe AD and comorbid pathology.

Materials and Methods. This case series presents data from 5 adult patients with severe refractory AD who received upadacitinib 30 mg/day for 52 weeks. Efficacy was assessed by dynamics in SCORAD, EASI, IGA, NRS, DLQI, and POEM scores. Gene expression of cytokines (TARC/CCL17, MDC/CCL22, PARC/CCL18, CTACK/CCL27, eotaxin-3/CCL26, IL-4, IL-13, IL-17, IL-22, TSLP, IL-25, IL-33) was analyzed using PCR at baseline and week 16 of therapy.

Results. Disease control was achieved in all patients: by week 40, 100% of patients (5/5) achieved EASI-90 response, which was maintained until the end of the observation period. Median SCORAD decreased from 65.3 to 2.7 by week 16, while median EASI score decreased from 47.6 to 0.7 by week 28. Pruritus intensity (NRS) decreased from 5 to 1 (median) by week 16. Twenty-six mild adverse events were recorded; no serious adverse events were reported. Complete drug-induced remission was observed in one female patient with comorbid alopecia areata. No statistically significant changes were detected in the profile of the studied biomarkers.

Conclusion. In this case series, upadacitinib demonstrated high efficacy and a favorable safety profile in patients with severe refractory AD over 52 weeks of therapy. The observed remission of comorbid alopecia areata expands understanding of the drug's therapeutic potential. Larger prospective studies are needed to confirm these findings and to identify predictive biomarkers.