Upadacitinib has demonstrated efficacy in psoriatic arthritis in clinical trials, but its real-world performance in difficult-to-treat PsA remains underexplored. This observational, multicenter, open-label study evaluated the efficacy and safety of upadacitinib in 134 patients with psoriatic arthritis (97 women, mean age 51.8 ± 11.2 years, mean disease duration 9.94 ± 7.72 years) who showed inadequate response to advanced therapies. Most patients (74.6%) had received at least two biological/targeted synthetic disease-modifying antirheumatic drugs with different mechanisms of action. Upadacitinib was initiated at 15 mg daily, and within one month, significant improvements were observed: DAS28-ESR decreased from 4.7 to 3.77 (p < 0.001), DAPSA from 25 to 17 (p < 0.001), and CRP from 2.90 to 1.50 mg/L (p = 0.001). These reductions persisted throughout the study. Prednisone dosage decreased significantly (p = 0.049). Adverse events led to upadacitinib discontinuation in 8.2% of patients, but no serious adverse events were reported. Compared to the SELECT-PsA 2 trial, our cohort had a higher proportion of females and greater prior exposure to biologic agents but showed comparable efficacy and safety outcomes. These findings suggest that upadacitinib is a rapid, effective, and relatively safe therapeutic option for difficult-to-treat psoriatic arthritis under real-world conditions, supporting its use despite differing patient characteristics from clinical trial populations.

Background Upadacitinib (UPA) is an inhibitor of JAK kinases recently approved by EMA for the treatment of psoriatic arthritis (PsA) in Europe (January 2021) ^1. UPA has shown efficacy in refractory patients to anti-TNF ^2. Objectives A) to assess efficacy and safety of UPA in the first cases in Spain in clinical practice. B) to compare the profile of clinical practice patients with clinical trial of UPA in PsA refractory to biologics ². Methods Study of 39 patients of clinical practice with PsA treated with UPA in Spain. The diagnosis of PsA was made using CASPAR criteria. Patients who received at least one dose of UPA were included. Results are expressed as percentage, mean±SD or median [IRQ]. Results 39 patients (29♀/10♂), mean age of 51.5 ± 11.4 years (Table 1). Pattern joint involvement was as follows: peripheral (n=19), axial (3) and mixed (17) During the PsA evolution, patients also presented enthesitis (59%) nail involvement (28.2%) and dactylitis (35.9%). Prior to UPA, most patients (59%) had received oral prednisone or equivalent (max 9.03±12.12mg/d), synthetic immunosuppressants (mean1.8±0.9) and biological therapy (TB) (4.5±2.1). TB were as follows: etanercept (25), adalimumab (28), infliximab (12), golimumab (16), certolizumab (15), secukinumab (29), ustekinumab (21) Abatacept (2), brodalumab (1) and ixekizumab (17). Apremilast was used in 13, Tofacitinib in 11 and filgotinib in 1. After a mean follow-up of 12.41± 8.68.3 years after the PsA diagnosis, UPA was started (15 mg/24 h), 43.6% associated prednisone (7.35±3.36 mg/d). In 16 (41%) UPA was started in combined therapy: methotrexate (9), salazopyrin (3) and leflunomide (4); in the remaining 23 (59%), monotherapy was prescribed. At UPA onset patients presented peripheral arthritis (76.9%), axial involvement (35.8%), skin involvement (25.6%), enthesitis (41%), and dactylitis (10.3%). Patients of clinical practice compared with clinical trial there were more women, have a longer duration of PsA, and received a higher proportion of previous TB (Table 1). After a median follow-up of 4.28 ± 2.6 months, patients showed prompt improvement in activity indexes (DAS28, DAPSA) (Figure 1) and laboratory test (CRP mg/L decreased from 4.00 [1.5;10.0] to 0.40 [0.30;4.00] (p 0.024) at the sixth month. Extra-articular manifestations also improved: dactylitis in 25% patients, enthesitis (43.8%), skin involvement (40%) and onychopathy (50%). No serious events were reported. Minor side effects were reported in 7 patients (17.9%), and UPA was discontinued in 9 due to inefficiency. Conclusion In this preliminary study, first patients of clinical practice in Spain with UPA in PsA had a longer evolution and received a greater number of TB than those of clinical trial. As in the UPA clinical trial, it seems effective, rapid and relatively safe in daily clinical practice for refractory PsA. References [1]https://www.ema.europa.eu/en [2]Mease PJ, et al. Ann Rheum Dis 2021;80:312–320 Disclosure of Interests None declared