Long-Term Effectiveness of Upadacitinib in Difficult-to-Treat Psoriatic Arthritis: A 104-week Real-World Clinical and Ultrasound Study.

Background: Difficult-to-treat psoriatic arthritis (D2T PsA) represents a challenging condition characterized by inadequate response to multiple therapeutic agents. Real-world data on the effectiveness of Janus kinase inhibitors (JAKi) in this population remain limited. Objective: To evaluate the effectiveness, safety, and treatment persistence of Upadacitinib (UPA) in patients with D2T PsA using both clinical and ultrasound assessments. Patients and Methods: This observational retrospective study included patients with PsA who failed at least one conventional DMARD and two biologic DMARDs with different mechanisms of action. All patients received UPA 15 mg once daily as monotherapy. Treatment persistence was assessed over 140 weeks, while effectiveness data were collected at four time points following baseline (12, 24, 48, and 104 weeks). Clinical measures included: PASI; cDAPSA score; swollen/tender joints count; assessment of enthesitis and dactylitis; VAS scores for disease activity/pain; HAQ. At baseline and during the follow-up, ultrasound imaging was performed according to the EULAR-OMERACT ultrasound score. Results: Twenty-five patients were enrolled. After 140 weeks, treatment persistence was 68%. A rapid and sustained improvement in disease activity was observed, with mean cDAPSA decreasing from 27.88±5.2 at baseline to 12.04±8.17 at week 12 and 4.88±4.54 at week 52. At one year, 70.6% of patients achieved complete remission and 23.6% low disease activity. Ultrasound findings confirmed the clinical improvement, with a significant reduction in the EULAR-OMERACT score and complete resolution of enthesitis after one year of treatment. Most patients (94.1%) maintained complete remission or low disease activity up to week 104. Skin condition also improved significantly as demonstrated by the marked reduction in PASI score which decreased from a baseline value of 2.22 ± 2.62 to 0.21 ± 0.36 after 52 weeks of treatment. The safety profile was favorable, with mild lipid and CPK abnormalities being the most common adverse events. Conclusion: In this real-world cohort of patients with D2T PsA, UPA demonstrated sustained clinical and ultrasound effectiveness with a favorable safety profile and good long-term treatment persistence.