Real-world effectiveness and safety of upadacitinib in Japanese patients with rheumatoid arthritis: impact of age, renal function, and low-dose therapy

Upadacitinib (UPA) is an important therapeutic option for rheumatoid arthritis (RA), but evidence in older adults and patients with renal impairment remains limited. This study evaluated the real-world effectiveness and safety of UPA in Japanese patients with RA, including older adults and those with renal impairment. This multicenter retrospective study included 112 patients with RA who received UPA (7.5 or 15 mg/day), with clinical outcomes assessed up to 52 weeks based on medical record review. Effectiveness was assessed using the Disease Activity Score 28–erythrocyte sedimentation rate (DAS28-ESR), Clinical Disease Activity Index (CDAI), and Health Assessment Questionnaire–Disability Index (HAQ-DI). Safety was evaluated based on adverse events and laboratory findings. Predictors of response were explored using multivariable regression, and prespecified subgroup analyses were performed by age (≥ 75 vs. <75 years), renal function (eGFR < 60 vs. ≥60 mL/min/1.73 m²), and UPA dose (7.5 vs. 15 mg/day). At week 52, 87.5% of patients continued UPA, and 62.5% achieved DAS28-ESR remission (< 2.6). Significant improvements in DAS28-ESR and CDAI were observed and maintained through week 52. Similar improvements in disease activity were observed in patients aged ≥ 75 years and in those with renal impairment. Clinical response was associated with baseline disease activity, anti-cyclic citrullinated peptide antibody levels, rheumatoid factor titers, and prior biologic or targeted synthetic DMARD use. The 7.5 mg/day regimen was more frequently prescribed to older patients and those with renal impairment. UPA demonstrated sustained effectiveness and acceptable safety across clinically important subgroups of Japanese patients with RA, including older adults and those with renal impairment. These findings suggest the feasibility of individualized treatment strategies; however, dose comparisons should be interpreted cautiously given physician-driven prescribing.