Ab0215 Patterns of Use, Persistence and Cardiovascular Risk in Patients With Inflammatory Arthritis Treated With Upadacitinib in a Real-World Setting. Upareal Study

Background: Based mainly on results from a randomized clinical trial (RCT) in rheumatoid arthritis (RA) patients (ORAL Surveillance), major regulatory agencies have concluded that JAK inhibitors, including Upadacitinib (UPA), a selective and reversible JAK1 inhibitor, may be associated with an increased risk of serious cardiovascular events and cancer compared with tumor necrosis factor inhibitors (TNFi). In this context, evidence on safety, effectiveness and risk minimization measures in patients treated with UPA in routine clinical practice are of particular interest. Objectives: To evaluate changes in prescribing habits of one of the JAK inhibitors after the publication of the Oral Surveillance data. To assess the effectiveness and safety of UPA in real life. Methods: Observational, retrospective, multicenter study including patients diagnosed with RA, and spondyloarthritis (SpA) (psoriatic arthritis, and axial-SpA), who received UPA for at least 3 months between January 1, 2021 and March 31, 2023. For a comparison of baseline cardiovascular risk (CVR), RA and SpA patients who initiated TNFi treatment during this same period were also analyzed. Baseline demographic and disease characteristics, changes over time in DAS28 or BASDAI, baseline CVR by Systemic Coronary Risk Estimation (SCORE)2 or SCORE2_OP (patients >70 years), concomitant medications, line and persistence of UPA treatment, and adverse events data were collected. Cox regression and Kaplan-Meier curves were used to analyze the UPA persistence, and a general mixed linear model to study the variation of disease activity over time. Results: A total of 104 patients treated with UPA, 80 RA (77%) and 24 (23%) SpA, were included. Table 1 shows baseline demographic and disease characteristics, disease activity, and CVR factors, including baseline SCORE2 of patients treated with UPA and TNFi. To examine changes over time in CVR minimization in UPA-treated patients, 109 patients who initiated TNFi during the same period with similar demographic characteristics and clinical activity (Table 1) were analyzed as a comparator. SCORE2, both as a percentage (p=0.471) and categorized as low, moderate, or high risk (p=0.212), were similar between patients treated with UPA or TNFi (Table 1). However, when SCORE2 was categorized and analyzed by trimester, a significant reduction (p=0.033) was observed in moderate-high risk patients who initiated UPA versus TNFi since April 2022 (Table 2). UPA showed significant effectiveness in controlling RA disease activity by DAS28 during follow-up (p<0.001). UPA persistence in both RA and SpA patients was similar with apparently better persistence in SpA (log rank: 2.91, p=0.088). According to the COX regression analysis, the only factor associated with lower UPA persistence was its use in 2nd or higher line (HR 7.1 95%CI 0.98-52.08, p= 0.052). The main reason for discontinuation of UPA was adverse events (n=11, 44%), followed by ineffectiveness (n=8, 32%) and loss to follow-up (n=6, 24%). Conclusion: The recommendations of the regulatory authorities to minimize CVR in patients treated with JAKi seem to have been adopted and even anticipated in daily clinical practice. UPA shows sustained effectiveness in patients with RA and especially in those with SpA, with a safety profile equivalent to that shown in RCTs. Table 2. Contingency table of patients initiating UPA or TNFi with moderate-high cardiovascular risk by SCORE2 before and after April 2022. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests: María Vanesa Hernández Hernández Abbvie, Pfizer, BMS, Novartis, Cellgene, UCB, Grünenthal, Jannsen, Galapagos, Novartis, UCB, Cristina Martínez González: None declared, Cristina Rodriguez Regalado: None declared, Alicia García Dorta Abbvie, Novartis, Sonia Peña Montelongo: None declared, Elena Naveda: None declared, Enrique González Dávila: None declared, Federico Diaz Gonzalez Abbvie, Pfizer, Bristol, UCB, Galapagos, Novartis, Cellgene., Abbvie, UCB, Lilly, Galapagos, Novartis, Cellgene.