Risk Stratification of Patients with Psoriatic Arthritis and Ankylosing Spondylitis for Treatment with Tofacitinib: A Review of Current Clinical Data

IF 2.9 3区医学 Q2 RHEUMATOLOGY

Rheumatology and Therapy Pub Date : 2024-05-02 DOI:10.1007/s40744-024-00662-5

Lars Erik Kristensen, Atul Deodhar, Ying-Ying Leung, Ivana Vranic, Mahta Mortezavi, Lara Fallon, Arne Yndestad, Cassandra D. Kinch, Dafna D. Gladman

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Abstract

In this commentary, we review clinical data which helps inform individualized benefit–risk assessment for tofacitinib in patients with psoriatic arthritis (PsA) and ankylosing spondylitis (AS). ORAL Surveillance, a safety trial of patients ≥ 50 years of age with rheumatoid arthritis (RA) and cardiovascular risk factors, found increased rates of safety outcomes (including major adverse cardiovascular events [MACE], malignancies excluding non-melanoma skin cancer, and venous thromboembolism) with tofacitinib versus tumor necrosis factor inhibitors (TNFi). Post hoc analyses of ORAL Surveillance have identified subpopulations with different relative risk versus TNFi; higher risk with tofacitinib was confined to patients ≥ 65 years of age and/or long-time current/past smokers, and specifically for MACE, patients with a history of atherosclerotic cardiovascular disease (ASCVD). In patients without these risk factors, risk differences between tofacitinib and TNFi could not be detected. Given differences in demographics, pathophysiology, and comorbidities, we sought to examine whether the risk stratification observed in RA is also appropriate for PsA and AS. Data from the PsA tofacitinib development program show low absolute risk of safety outcomes in patients < 65 years of age and never smokers, and low MACE risk in patients with no history of ASCVD, consistent with results from ORAL Surveillance. No MACE, malignancies, or venous thromboembolism were reported in the tofacitinib AS development program. The mechanism of the ORAL Surveillance safety findings is unknown, and there are no similar prospective studies of sufficient size and duration. Accordingly, it is appropriate to use a precautionary approach and extrapolate differentiating risk factors identified from ORAL Surveillance (age ≥ 65 years, long-time current/past smoking, and history of ASCVD) to PsA and AS. We recommend an individualized approach to treatment decisions based on these readily identifiable risk factors, in line with updated labeling for Janus kinase inhibitors and international guidelines for the treatment of PsA and AS.

Trial Registration: NCT02092467, NCT01262118, NCT01484561, NCT00147498, NCT00413660, NCT00550446, NCT00603512, NCT00687193, NCT01164579, NCT00976599, NCT01059864, NCT01359150, NCT02147587, NCT00960440, NCT00847613, NCT00814307, NCT00856544, NCT00853385, NCT01039688, NCT02281552, NCT02187055, NCT02831855, NCT00413699, NCT00661661, NCT01877668, NCT01882439, NCT01976364, NCT00678210, NCT01710046, NCT01241591, NCT01186744, NCT01276639, NCT01309737, NCT01163253, NCT01786668, NCT03502616.

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银屑病关节炎和强直性脊柱炎患者接受托法替尼治疗的风险分层：当前临床数据回顾

在这篇评论中，我们回顾了有助于为银屑病关节炎（PsA）和强直性脊柱炎（AS）患者进行托法替尼个体化获益-风险评估提供信息的临床数据。ORAL Surveillance是一项针对年龄≥50岁、患有类风湿性关节炎（RA）和心血管风险因素的患者进行的安全性试验，结果发现，与肿瘤坏死因子抑制剂（TNFi）相比，托法替尼的安全性结果（包括主要不良心血管事件[MACE]、恶性肿瘤（不包括非黑色素瘤皮肤癌）和静脉血栓栓塞）发生率更高。ORAL监测的事后分析确定了与TNFi相比具有不同相对风险的亚人群；使用托法替尼的较高风险仅限于年龄≥65岁和/或目前/过去长期吸烟的患者，特别是对于MACE而言，仅限于有动脉粥样硬化性心血管疾病（ASCVD）病史的患者。在没有这些风险因素的患者中，无法发现托法替尼和 TNFi 之间的风险差异。鉴于人口统计学、病理生理学和合并症方面的差异，我们试图研究在RA中观察到的风险分层是否也适用于PsA和AS。PsA托法替尼开发项目的数据显示，65岁以上从不吸烟的患者绝对安全风险较低，无ASCVD病史的患者MACE风险较低，这与ORAL Surveillance的结果一致。在托法替尼AS开发项目中，没有出现MACE、恶性肿瘤或静脉血栓栓塞的报道。ORAL Surveillance安全性研究结果的机制尚不清楚，也没有规模足够大、持续时间足够长的类似前瞻性研究。因此，采用预防性方法并将ORAL监测中发现的不同风险因素（年龄≥65岁、当前/过去长期吸烟以及ASCVD病史）外推至PsA和AS是合适的。我们建议根据这些易于识别的风险因素采取个体化的治疗决策，以符合Janus激酶抑制剂的最新标签以及治疗PsA和AS的国际指南：NCT02092467, NCT01262118, NCT01484561, NCT00147498, NCT00413660, NCT00550446, NCT00603512, NCT00687193, NCT01164579、NCT00976599, NCT01059864, NCT01359150, NCT02147587, NCT00960440, NCT00847613, NCT00814307, NCT00856544, NCT00853385、NCT01039688, NCT02281552, NCT02187055, NCT02831855, NCT00413699, NCT00661661, NCT01877668, NCT01882439, NCT01976364、NCT00678210, NCT01710046, NCT01241591, NCT01186744, NCT01276639, NCT01309737, NCT01163253, NCT01786668, NCT03502616.

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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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