Achievement and Maintenance of Disease Targets with Upadacitinib in Rheumatoid Arthritis: 2-Year Outcomes from the UPHOLD Real-World Study.

IF 3.1 3区医学 Q2 RHEUMATOLOGY

Rheumatology and Therapy Pub Date : 2026-06-01 Epub Date: 2026-03-19 DOI:10.1007/s40744-026-00826-5

Andrew Östör, Eugen Feist, Prodromos Sidiropoulos, Jérôme Avouac, Martin Rebella, Rajaie Namas, Frank Buttgereit, Philip G Conaghan, Ana B Romero, Erin L McDearmon-Blondell, Ivan Lagunes-Galindo, Tianming Gao, Aditi Kadakia, Tim Shaw, Suzan Attar

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引用次数: 0

Abstract

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.

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Upadacitinib治疗类风湿关节炎的疾病目标的实现和维持：来自秉持真实世界研究的2年结果

Upadacitinib是一种口服Janus激酶抑制剂，在类风湿关节炎（RA）临床试验中显示出良好的获益-风险分析。该分析旨在评估upadacitinib在24个月的长期有效性和安全性。方法：主要终点为：(1)28个关节中c反应蛋白（DAS28[CRP]）缓解达到疾病活动性评分的患者比例(结果：总共有1029/1715例（60.0%）患者完成了24个月的随访。6个月时DAS28（CRP）反应良好地维持到24个月（mNRI/AO缓解，分别为62.9%/83.9%；LDA，分别为65.7%/90.1%）。24个月时，维持联合治疗和单一治疗的患者缓解率一致（分别为81.1%和87.4%；AO）。在先前的治疗亚组中，反应也大致相似。在12个月期间取得的PROs改善维持到24个月。大多数在基线接受gc治疗的患者在24个月时达到无gc缓解。在选定的teae中，带状疱疹、严重感染和肝脏疾病的发生率分别为3.5、3.1和2.6 E/100 PY。没有发现新的安全信号。结论：Upadacitinib在现实世界的实践中对RA的长期治疗是有效的，在6个月时达到的反应维持到2年，没有新的安全性发现。试验注册：NCT04497597。

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来源期刊

Rheumatology and Therapy RHEUMATOLOGY-

CiteScore

6.00

自引率

5.30%

发文量

审稿时长

6 weeks

期刊介绍： Aims and Scope Rheumatology and Therapy is an international, open access, peer reviewed, rapid publication journal dedicated to the publication of high-quality clinical (all phases), observational, real-world and health outcomes research around the discovery, development, and use of rheumatologic therapies. Studies relating to diagnosis, pharmacoeconomics, public health, quality of life, and patient care, management, and education are also welcomed. Areas of focus include, but are not limited to, rheumatoid arthritis, gout, gouty arthritis, psoriatic arthritis, osteoarthritis, juvenile idiopathic/rheumatoid arthritis, systemic lupus erythematosus, axial spondyloarthritis, Pompe’s disease, inflammatory joint conditions, musculoskeletal conditions, systemic sclerosis, and fibromyalgia. The journal is of interest to a broad audience of healthcare professionals and publishes original research, reviews, case reports, trial protocols, communications and letters. The journal is read by a global audience and receives submissions from all over the world. Rheumatology and Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an international and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of all scientifically and ethically sound research. Ethics and Disclosures The journal is a member of the Committee on Publication Ethics (COPE) and subscribes to its principles on how to deal with acts of misconduct thereby committing to investigate allegations of misconduct in order to ensure the integrity of research. Content in this journal is peer-reviewed (Single-blind). For more information on our publishing ethics policies, please see here: https://www.springer.com/gp/editorial-policies Rapid Publication The journal’s rapid publication timelines aim for a peer review decision within 2 weeks of submission. If an article is accepted it will be published online 3-4 weeks from acceptance. These rapid timelines are achieved through the combination of a dedicated in-house editorial team, who closely manage article workflow, and an extensive Editorial and Advisory Board who assist with rapid peer review. This allows the journal to support the rapid dissemination of research, whilst still providing robust peer review. Combined with the journal’s open access model this allows for the rapid and efficient communication of the latest research and reviews, allowing the advancement of rheumatologic therapies. 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