Real-world effectiveness and safety of upadacitinib in moderate-to-severe rheumatoid arthritis: Subgroup analysis for 1-year outcomes of UPHOLD study in Gulf Cooperation Council

BACKGROUND: Rheumatoid arthritis (RA), a chronic autoimmune disease, is increasingly prevalent in the Middle East. Although treatment guidelines are informed by randomized controlled trials, real-world evidence on the long-term effectiveness and safety of Janus kinase inhibitors such as upadacitinib (UPA) in Gulf Cooperation Council (GCC) countries remains limited. OBJECTIVE: To evaluate the effectiveness and safety of long-term UPA 15 mg once daily in patients from GCC countries with moderate-to-severe RA, focusing on treatment targets and response maintenance in real-world settings. METHODOLOGY: This is a subgroup analysis of the UPHOLD trial (NCT04497597), a prospective, multicenter, noninterventional study. UPA-naïve adults with moderate-to-severe RA received UPA 15 mg once daily as monotherapy or combined with other disease-modifying antirheumatic drugs. Co-primary endpoints were DAS28-CRP remission (<2.6) at 6 months and its maintenance at 12 months. Safety was also assessed. RESULTS: Of 94 patients enrolled, 43.9% achieved DAS28-CRP remission at 6 months, and 81.8% maintained remission at 12 months. In addition, 52.6% achieved low disease activity (LDA) at 6 months, with 81.8% maintaining it at 12 months. Patient-reported outcomes (Patient’s Global Assessment and Health Assessment Questionnaire Disability Index scores) improved significantly. Treatment-emergent adverse events (TEAEs) were reported in 45.7%, most of which were mild (33%) or moderate (27.7%) in severity. Severe and serious TEAEs occurred in 6.4% and 8.5%, respectively. No new safety signals were identified. CONCLUSION: UPA 15 mg once daily demonstrated effectiveness in achieving and maintaining remission and LDA in patients with moderate-to-severe RA in real-world clinical practice from GCC countries, with a manageable safety profile.