Methotrexate, Tofacitinib, and Biologic Disease-Modifying Antirheumatic Drug Safety and Effectiveness Among Patients with Rheumatoid Arthritis in Japan: CorEvitas Registry Observational Study

IF 2.9 3区医学 Q2 RHEUMATOLOGY

Rheumatology and Therapy Pub Date : 2024-07-27 DOI:10.1007/s40744-024-00700-2

Yoshiya Tanaka, Mitsumasa Kishimoto, Koshiro Sonomoto, Koichi Amano, Masayoshi Harigai, Alina Onofrei, Jacqueline O’Brien, Zachary Margolin, Christine Barr, Yasushi Mizuno, Ekta Agarwal, Naonobu Sugiyama, Hisashi Yamanaka

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引用次数: 0

Abstract

Introduction

The evolution of disease-modifying antirheumatic drugs (DMARDs) for the treatment of rheumatoid arthritis (RA) has improved patient prognosis. However, more real-world safety/effectiveness data comparing methotrexate (MTX), tofacitinib, tumor necrosis factor inhibitors (TNFi), and non-TNFi biologic DMARDs (bDMARDs) are warranted.

Methods

The CorEvitas RA Japan registry was used to identify patients with rheumatologist-diagnosed RA who initiated MTX/tofacitinib/TNFi/non-TNFi bDMARDs. Safety outcomes included incidence of major adverse cardiovascular events (MACE), total cardiovascular disease, total serious infections, total herpes zoster, and total malignancies (excluding non-melanoma skin cancer). Effectiveness outcomes included change from baseline (Δ) in Clinical Disease Activity Index (CDAI) and proportion of patients achieving a minimum clinically important difference (MCID) in CDAI at month 6. Adjusted regression models were fit; marginal means were estimated.

Results

Overall, 1972 patients were included in the safety cohort: MTX (N = 298); tofacitinib (N = 253); TNFi (N = 663); non-TNFi (N = 758). Mean follow-up time was 3.8, 2.9, 3.0, and 2.9 years for MTX, tofacitinib, TNFi, and non-TNFi, respectively. Adjusted incidence rates (IRs, patients with events/100 patient-years [95% confidence intervals]) for MACE and total cardiovascular disease, respectively, were numerically lower for MTX (0.34 [0, 0.83]; 0.42 [0, 0.92]) and TNFi (0.09 [0, 0.27]; 0.61 [0.15, 1.07]) versus tofacitinib (0.48 [0, 1.20]; 2.30 [0.38, 4.22]) and non-TNFi (0.77 [0.35, 1.19]; 1.28 [0.73, 1.82]). Serious infections were numerically higher for non-TNFi (4.47 [3.38, 5.56]); herpes zoster was higher for tofacitinib (7.41 [4.52, 10.29]), versus other groups. IRs for malignancies were comparable between groups. Mean ΔCDAI and rates of achieving MCID in CDAI at month 6 were generally greater with tofacitinib versus other groups.

Conclusion

Some variations in incidence of safety outcomes were observed between treatments, while certain effectiveness outcomes favored tofacitinib. Sample size variation between groups and low number of safety events limited the analysis. Further studies are warranted to investigate observed differences.

ClinicalTrials.gov

NCT05572567.

Abstract Image

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日本类风湿关节炎患者服用甲氨蝶呤、托法替尼和生物制剂改变病情抗风湿药物的安全性和有效性：CorEvitas 登记观察研究

导言用于治疗类风湿性关节炎（RA）的改变病情抗风湿药（DMARDs）的发展改善了患者的预后。然而，我们需要更多真实世界的安全性/有效性数据，对甲氨蝶呤（MTX）、托法替尼、肿瘤坏死因子抑制剂（TNFi）和非TNFi生物DMARDs（bDMARDs）进行比较。方法：CorEvitas RA日本登记处用于识别经风湿免疫科确诊、开始使用MTX/托法替尼/TNFi/非TNFi bDMARDs的RA患者。安全性结果包括主要心血管不良事件（MACE）发生率、心血管疾病总数、严重感染总数、带状疱疹总数和恶性肿瘤总数（不包括非黑色素瘤皮肤癌）。疗效结果包括临床疾病活动指数（CDAI）与基线相比的变化（Δ）以及第6个月时CDAI达到最小临床意义差异（MCID）的患者比例。结果总体而言，1972名患者被纳入安全性队列：MTX（N = 298）；托法替尼（N = 253）；TNFi（N = 663）；非TNFi（N = 758）。MTX、托法替尼、TNFi和非TNFi的平均随访时间分别为3.8年、2.9年、3.0年和2.9年。MACE和总心血管疾病的调整后发病率（IRs，事件患者/100患者年[95%置信区间]）分别为MTX较低（0.34[0，0.83]；0.42[0，0.92]）和 TNFi（0.09[0，0.27]；0.61[0.15，1.07]）在数值上低于托法替尼（0.48[0，1.20]；2.30[0.38，4.22]）和非 TNFi（0.77[0.35，1.19]；1.28[0.73，1.82]）。非 TNFi（4.47 [3.38, 5.56]）的严重感染率更高；托法替尼（7.41 [4.52, 10.29]）的带状疱疹感染率高于其他组别。各组间恶性肿瘤的IR值相当。平均ΔCDAI和第6个月时CDAI的MCID达标率，托法替尼普遍高于其他组。组间样本量的差异和较低的安全事件数量限制了分析。有必要开展进一步研究，以调查观察到的差异。ClinicalTrials.govNCT05572567。

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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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