Malignancy in the Upadacitinib Clinical Trials for Rheumatoid Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis, and Non-radiographic Axial Spondyloarthritis.

IF 2.9 3区医学 Q2 RHEUMATOLOGY

Rheumatology and Therapy Pub Date : 2024-02-01 Epub Date: 2023-11-20 DOI:10.1007/s40744-023-00621-6

Andrea Rubbert-Roth, Adriana M Kakehasi, Tsutomu Takeuchi, Marc Schmalzing, Hannah Palac, Derek Coombs, Jianzhong Liu, Samuel I Anyanwu, Ralph Lippe, Jeffrey R Curtis

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引用次数: 0

Abstract

Introduction: This article aims to describe malignancies in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), or non-radiographic axial spondyloarthritis (nr-axSpA) treated with upadacitinib (UPA) or active comparators.

Methods: This integrated safety analysis includes data from 11 phase 3 UPA trials across RA (6 trials), PsA (2 trials), AS (2 trials; one phase 2b/3), and nr-axSpA (1 trial). Treatment-emergent adverse events (TEAEs) were summarized for RA (pooled UPA 15 mg [UPA15], pooled UPA 30 mg [UPA30], adalimumab 40 mg [ADA], methotrexate monotherapy [MTX]), PsA (pooled UPA15, pooled UPA30, ADA), AS (pooled UPA15), and nr-axSpA (UPA15). TEAEs were reported as exposure-adjusted event rates (events/100 patient-years).

Results: Median treatment duration ranged from 1.0 to 4.0 years (with a maximum of 6.6 years in RA). Across treatments and indications, rates of malignancy excluding nonmelanoma skin cancer (NMSC) ranged from 0.2 to 1.1, while NMSC ranged from 0.0 to 1.4. In RA, rates of malignancy excluding NMSC were generally similar between UPA15, UPA30, ADA, and MTX (breast and lung cancer were the most common). In RA and PsA, Kaplan-Meier analyses revealed no differences in event onset of malignancy excluding NMSC with UPA15 versus UPA30 over time. In RA, NMSC rates were higher with UPA30 than UPA15; both UPA15 and UPA30 were higher than ADA and MTX. In PsA, rates of malignancy excluding NMSC and NMSC were generally similar between UPA15, UPA30, and ADA. In AS and nr-axSpA, malignancies were reported infrequently. Few events of lymphoma were reported across the clinical programs.

Conclusion: Rates of malignancy excluding NMSC were generally similar between UPA15, UPA30, ADA, and MTX and were consistent across RA, PsA, AS, and nr-axSpA. A dose-dependent increased rate of NMSC was observed with UPA in RA.

Trial registration: ClinicaTrials.gov identifier: NCT02706873, NCT02675426, NCT02629159, NCT02706951, NCT02706847, NCT03086343, NCT03104400, NCT03104374, NCT03178487, and NCT04169373.

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Upadacitinib临床试验治疗类风湿关节炎、银屑病关节炎、强直性脊柱炎和非影像学中轴性脊柱炎的恶性肿瘤。

简介:本文旨在描述用upadacitinib (UPA)或活性比较物治疗类风湿关节炎(RA)、银屑病关节炎(PsA)、强直性脊柱炎(AS)或非放射性轴性脊柱炎(nr-axSpA)患者的恶性肿瘤。方法:这项综合安全性分析包括11项3期UPA试验的数据，包括RA(6项试验)、PsA(2项试验)、AS(2项试验;1个2b/3期)和nr-axSpA(1个试验)。总结了RA(合并UPA15 mg [UPA15]、合并UPA30 mg [UPA30]、阿达木单抗40 mg [ADA]、甲氨喋呤单药[MTX])、PsA(合并UPA15、合并UPA30、ADA)、AS(合并UPA15)和nn - axspa (UPA15)的治疗不良事件(teae)。teae以暴露调整事件率(事件数/100患者年)报告。结果:中位治疗时间范围为1.0至4.0年(RA最长为6.6年)。在治疗和适应症中，不包括非黑色素瘤皮肤癌(NMSC)的恶性肿瘤发生率从0.2到1.1不等，而NMSC的发生率从0.0到1.4不等。在RA中，UPA15、UPA30、ADA和MTX的恶性肿瘤发生率(不包括NMSC)大致相似(乳腺癌和肺癌最常见)。在RA和PsA中，Kaplan-Meier分析显示，随着时间的推移，UPA15与UPA30在排除NMSC的恶性肿瘤事件发作方面没有差异。在RA中，UPA30组的NMSC发生率高于UPA15组;UPA15和UPA30均高于ADA和MTX。在PsA中，UPA15、UPA30和ADA之间除NMSC和NMSC外的恶性肿瘤发生率大致相似。在AS和nr-axSpA中，恶性肿瘤的报道很少。在整个临床项目中很少有淋巴瘤的报道。结论:除NMSC外，UPA15、UPA30、ADA和MTX的恶性肿瘤发生率基本相似，RA、PsA、AS和nr-axSpA的恶性肿瘤发生率基本一致。在RA中，UPA可使NMSC呈剂量依赖性增加。试验注册:ClinicaTrials.gov识别码:NCT02706873、NCT02675426、NCT02629159、NCT02706951、NCT02706847、NCT03086343、NCT03104400、NCT03104374、NCT03178487和NCT04169373。

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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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