Introduction: Upadacitinib, an oral Janus kinase inhibitor, has shown a favorable benefit-risk profile in rheumatoid arthritis (RA) clinical trials. This analysis aimed to assess the long-term effectiveness and safety of upadacitinib through 24 months in the UPHOLD real-world observational study.
Methods: The coprimary endpoints were: (1) proportion of patients achieving disease activity score in 28 joints using C-reactive protein (DAS28[CRP]) remission (< 2.6) at 6 months; and (2) proportion of those patients who maintained remission at 12 months. Additional endpoints assessed through 24 months included: achievement and maintenance of DAS28(CRP) low disease activity (LDA; ≤ 3.2); maintenance of response by treatment strategy and prior therapy; disease category by visit; improvements in patient-reported outcomes (PROs); and achievement of glucocorticoid (GC)-free remission. Endpoints were analyzed by modified nonresponder imputation (mNRI) and as observed (AO). Exposure-adjusted event rates (events/100 patient-years [E/100 PY]) for treatment-emergent adverse events (TEAEs) were reported through May 15, 2024.
Results: In total, 1029/1715 (60.0%) patients completed the 24-month follow-up. DAS28(CRP) responses at 6 months were well maintained through 24 months (mNRI/AO remission, 62.9%/83.9%; and LDA, 65.7%/90.1%, respectively). Remission rates at 24 months were consistent between patients maintaining combination therapy and those maintaining monotherapy (81.1% and 87.4%, respectively; AO). Responses were also largely similar across prior therapy subgroups. Improvements in PROs achieved by 12 months were maintained through 24 months. Most patients receiving GCs at baseline who achieved GC-free remission maintained GC-free remission at 24 months. Among selected TEAEs of interest, herpes zoster, serious infection, and hepatic disorder occurred at 3.5, 3.1, and 2.6 E/100 PY, respectively. No new safety signals were identified.
Conclusions: Upadacitinib was effective for the long-term treatment of RA in real-world practice, with responses achieved at 6 months maintained through 2 years, and no new safety findings.
Trial registration: NCT04497597.
Keywords: Effectiveness; Real-world; Rheumatoid arthritis; Safety; Upadacitinib.
© 2026. The Author(s).