Upadacitinib in Patients with Moderate-to-Severe Rheumatoid Arthritis: 2-Year Data from Germany, Austria, and Switzerland in the Observational UPHOLD Study

INTRODUCTION: Upadacitinib (UPA), an oral JAK inhibitor, has demonstrated efficacy and an acceptable safety profile in rheumatoid arthritis (RA) clinical trials, but real-world (RW) long-term data are limited. This sub-analysis of UPHOLD evaluated the long-term effectiveness and safety of UPA over 2 years in adults with moderate-to-severe RA in Germany, Austria, and Switzerland. METHODS: UPHOLD (NCT04497597) is an international, observational cohort study of adults with moderate-to-severe RA in whom the treating physician decided to initiate treatment with UPA 15 mg once daily prior to study enrollment. Effectiveness was assessed using disease activity measures, including the Disease Activity Score in 28 joints using C-reactive protein (DAS28-CRP), as well as patient-reported outcomes (PROs). Endpoints were analyzed by modified nonresponder imputation (mNRI) and as observed (AO). All treatment-emergent adverse events (TEAEs), including selected TEAEs of interest, are reported as exposure-adjusted event rates (events per 100 patient-years [E/100PY]). RESULTS: Of the 268 patients who were enrolled, 262 received at least one UPA dose and 150 (56.0%) completed 2 years. More than half achieved DAS28-CRP responses at month 6 (mNRI/AO remission, 58.8%/71.0%; and LDA, 66.3%/80.0%, respectively) and these responses were maintained through year 2 (mNRI/AO remission, 59.6%/82.4%; and LDA, 61.5%/89.3%, respectively). Among patients with available data at year 2, 68.3% achieved DAS28-CRP remission. Remission rates were consistent between monotherapy and combination therapy, regardless of prior treatments. Improvements in PROs were seen at 3 months and maintained or improved through 2 years. There were 435 TEAEs (50 serious). Due to the limited sample size and exposure time, caution is advised in interpreting safety; however, the safety profile was similar to prior phase 3 trials. CONCLUSIONS: UPA showed sustained effectiveness and a consistent safety profile over 2 years in routine RW practice. Among month-6 responders, remission was maintained through year 2 in the majority of patients. Among all patients assessed at year 2, two-thirds were in DAS28-CRP remission.