Geographical Differences in the Safety and Efficacy of Tofacitinib Versus TNFi: A Post Hoc Analysis of ORAL Surveillance.

IF 2.9 3区医学 Q2 RHEUMATOLOGY Rheumatology and Therapy Pub Date : 2024-10-01 Epub Date: 2024-07-26 DOI:10.1007/s40744-024-00693-y

Bogdan Batko, Slawomir Jeka, Piotr Wiland, Agnieszka Zielińska, Maria Stopińska-Polaszewska, Marcin Stajszczyk, Magdalena Kosydar-Piechna, Mary Jane Cadatal, Jose L Rivas

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Abstract

Introduction: In ORAL Surveillance, incidence rates (IRs) of major adverse cardiovascular events (MACE) and malignancies (excluding non-melanoma skin cancer [NMSC]) in cardiovascular (CV)-risk-enriched patients with rheumatoid arthritis (RA) were numerically greater with tofacitinib in North America versus the rest of the world, due to underlying risk factors. Here, we evaluated the safety and efficacy of tofacitinib versus tumor necrosis factor inhibitors (TNFi) among patients with RA across geographical regions.

Methods: Patients with RA in ORAL Surveillance (NCT02092467), who were aged ≥ 50 years with ≥ 1 additional CV risk factor, received tofacitinib 5 or 10 mg twice daily or TNFi; 45.9% were from either Poland or North America. This post hoc analysis stratified patients by region (Poland, North America, Other countries). Efficacy endpoints included Clinical Disease Activity Index, Disease Activity Score in 28 joints, with C-reactive protein (DAS28-4[CRP]), and Health Assessment Questionnaire-Disability Index (HAQ-DI). IRs and hazard ratios for adverse events were reported.

Results: Of 4362 patients (Poland, N = 759; North America, N = 1243; Other countries, N = 2360), more patients from North America versus Poland/Other countries had CV risk factors such as body mass index ≥ 30 kg/m² and history of diabetes/hypertension; however, more patients from Poland versus other regions were ever smokers and more patients from Poland/North America versus Other countries had history of coronary artery disease. MACE IRs were similar in North America and Poland, and numerically higher versus Other countries. IRs for malignancies (excluding NMSC) were numerically higher in North America versus Poland/Other countries with tofacitinib. Serious infections IRs were numerically higher in North America versus Poland across treatments. Venous thromboembolism/all-cause mortality IRs were generally comparable across regions. DAS28-4(CRP)/HAQ-DI improvements were generally lowest in North America.

Conclusions: Differences in safety outcomes were driven by the presence of baseline risk factors; North America and Poland demonstrated a higher proportion of patients with some baseline CV risk factors/comorbidities versus Other countries.

Trial registration: NCT02092467 (ClinicalTrials.gov).

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托法替尼与 TNFi 的安全性和有效性的地域差异：口服监测的事后分析。

简介：在ORAL监测中，由于潜在风险因素的影响，北美地区类风湿关节炎（RA）患者使用托法替尼后，主要不良心血管事件（MACE）和恶性肿瘤（不包括非黑色素瘤皮肤癌[NMSC]）的发病率（IRs）高于世界其他地区。在此，我们评估了不同地区类风湿关节炎患者使用托法替尼与肿瘤坏死因子抑制剂（TNFi）的安全性和有效性：ORAL监测（NCT02092467）中的RA患者年龄≥50岁，有≥1个额外的CV风险因素，接受托法替尼5或10毫克，每天两次或TNFi治疗；45.9%的患者来自波兰或北美。这项事后分析按地区（波兰、北美、其他国家）对患者进行了分层。疗效终点包括临床疾病活动指数、28个关节的疾病活动评分和C反应蛋白（DAS28-4[CRP]），以及健康评估问卷-残疾指数（HAQ-DI）。结果：在4362名患者中（波兰，759人；北美，1243人；其他国家，2360人），北美与波兰/其他国家相比，有更多患者存在CV风险因素，如体重指数≥30 kg/m2和糖尿病/高血压病史；然而，波兰与其他地区相比，有更多患者曾经吸烟，波兰/北美与其他国家相比，有更多患者有冠心病病史。北美洲和波兰的 MACE IRs 相似，但在数量上高于其他国家。使用托法替尼治疗恶性肿瘤（不包括NMSC）的IR值在北美高于波兰/其他国家。在所有治疗方法中，北美的严重感染 IRs 在数值上高于波兰。不同地区的静脉血栓栓塞症/全因死亡率IR值基本相当。北美地区的DAS28-4（CRP）/HAQ-DI改善率普遍最低：基线风险因素的存在导致了安全性结果的差异；与其他国家相比，北美和波兰具有某些基线 CV 风险因素/合并症的患者比例更高：NCT02092467（ClinicalTrials.gov）。

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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. Personal Service The journal’s dedicated in-house editorial team offer a personal “concierge service” meaning that authors will always have a personal point of contact able to update them on the status of their manuscript. The editorial team check all manuscripts to ensure that articles conform to the most recent COPE, GPP and ICMJE publishing guidelines. This supports the publication of ethically sound and transparent research. We also encourage pre-submission enquiries and are always happy to provide a confidential assessment of manuscripts. Digital Features Rheumatology and Therapy offers a range of additional features designed to increase the visibility, readership and educational value of the journal’s content. Each article is accompanied by key summary points, giving a time-efficient overview of the content to a wide readership. 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For further information about digital features, please contact the journal editor (see ‘Contact the Journal’ for email address), and see the ‘Guidelines for digital features and plain language summaries’ document under ‘Submission guidelines’. For examples of digital features please visit: https://springerhealthcare.com/expertise/publishing-digital-features/ Preprints We encourage posting of preprints of primary research manuscripts on preprint servers, authors'' or institutional websites, and open communications between researchers whether on community preprint servers or preprint commenting platforms. Posting of preprints is not considered prior publication and will not jeopardize consideration in our journals. Authors should disclose details of preprint posting during the submission process or at any other point during consideration in the journal. 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At least two extensive reviews are required to make the editorial decision. Where reviewer recommendations are conflicted, the editorial board will be contacted for further advice and a presiding decision. Manuscripts are then either accepted, rejected or authors are required to make major or minor revisions (both reviewer comments and editorial comments may need to be addressed). Once a revised manuscript is re-submitted, it is assessed along with the responses to reviewer comments and if it has been adequately revised it will be accepted for publication. Accepted manuscripts are then copyedited and typeset by the production team before online publication. Appeals against decisions following peer review are considered on a case-by-case basis and should be sent to the journal editor, and authors are welcome to make rebuttals against individual reviewer comments if appropriate. Considering the time and effort required for a detailed peer review we reward our regular reviewers with the opportunity to publish without publication fees (pending peer review) for every three reviews completed per calendar year. Copyright Rheumatology and Therapy is published under the Creative Commons Attribution-Noncommercial License, which allows users to read, copy, distribute, and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited. The author assigns the exclusive right to any commercial use of the article to Springer. For more information about the Creative Commons Attribution-Noncommercial License, click here: http://creativecommons.org/licenses/by-nc/4.0. Publication Fees Upon acceptance of an article, authors will be required to pay the mandatory Rapid Service Fee of €5,250/$6,000/£4,300. 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