Real-world data on treatment persistence and measures to minimize cardiovascular risk in rheumatic patients using upadacitinib.

Abstract

Upadacitinib (UPA), like other Janus kinase inhibitors (JAKis), has regulatory safety warnings related to cardiovascular risk (CVR) and malignancy. This study aims to identify clinical and demographic factors associated with UPA treatment persistence and to assess the impact of CVR safety regulatory recommendations on its prescription patterns in real-world clinical settings. The UPAreal is an observational, multicentre study involving 306 RA and SpA patients who initiated treatment with UPA (n = 153) or TNF inhibitors (TNFis) (n = 153) between January 2021 and December 2023. Data collected included baseline demographics, CVR assessed by SCORE2, concomitant medications, treatment line, treatment history and disease activity. Kaplan-Meier curves and Cox regression were used to analyse UPA persistence and its associated factors. Changes in baseline CVR for UPA- and TNFi-treated patients were examined over time using contingency tables and a general linear model with a treatment * date interaction. RA and SpA patients showed a similar UPA persistence with averages of 23.9 ± 1.5 and 22.8 ± 1.7 months, respectively. Cox analysis only identified prior use of IL-6 inhibitors (IL-6is) as associated with reduced UPA persistence in RA patients (HR: 2.05, 95%CI: 1.2; 3.49, P = 0.008). Disease activity indices showed significant improvements over 3 years (P < 0.001). From February 2022, patients initiating UPA exhibited a significantly lower basal CVR (P = 0.042) compared with those beginning TNFi. In real-world clinical settings, UPA persistence is lower among RA patients who have received prior IL-6i treatment. Treatment strategies to avoid UPA in patients with CVR appear to be primarily driven by pivotal safety studies rather than regulatory guidance.