按心血管风险富集度划分的托法替尼在加拿大类风湿关节炎患者中的安全性和有效性：CANTORAL 研究的子分析。

IF 2.9 3区医学 Q2 RHEUMATOLOGY

Rheumatology and Therapy Pub Date : 2024-12-01 Epub Date: 2024-11-01 DOI:10.1007/s40744-024-00719-5

Boulos Haraoui, Majed Khraishi, Denis Choquette, Isabelle Fortin, Cassandra D Kinch, Corina Galos, Patrice Roy, David Gruben, Julie Vaillancourt, John S Sampalis, Edward C Keystone

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引用次数: 0

摘要

简介：ORAL Surveillance是一项针对类风湿性关节炎（RA）患者进行的授权后安全性研究，研究结果显示，与肿瘤坏死因子抑制剂（TNFi）相比，托法替尼增加了主要不良CV事件（MACE）和恶性肿瘤（不包括非黑色素瘤皮肤癌[NMSC]）的风险。这项对加拿大真实世界观察性研究的分析评估了符合或不符合CV风险标准的患者服用托法替尼的安全性/有效性：CANTORAL纳入了开始服用托法替尼的中重度RA患者（10/2017-07/2020；N = 504）。中期数据（数据截止日期：2021年7月）被分层为有CV风险（CV+；患者年龄≥50岁，有≥1个额外的CV风险因素）或无CV风险（CV-；年龄≥50岁，无额外的CV风险因素，18-49岁，有/无CV风险因素）。安全性和持续性评估持续到第 36 个月。M18的疗效结果包括临床疾病活动指数（CDAI）定义的低疾病活动度（LDA）/缓解（CANTORAL共同主要终点）和28个关节的疾病活动度评分、C反应蛋白（DAS28-4[CRP]）结果：总体而言，272/232 名患者被纳入 CV+ /CV- 组群（完整分析集）（435/356 患者年[安全分析集]）。CV+ /CV-队列中治疗突发不良事件（AEs）的发生率（事件/100 患者年）为 138.5/112.5；严重 AEs 为 17.0/5.6；死亡为 1.2/0.3；严重感染为 5.严重感染为5/1.7；带状疱疹为1.4/1.1；MACE为1.6/0.0；恶性肿瘤（不包括NMSC）为2.1/0.3；NMSC为0.7/0.6；静脉血栓栓塞事件为0.5/0.0。各组间的持续率基本相当。在CV+/CV-队列中，M6时，CDAI LDA和缓解率分别为51.5%/54.6%和12.0%/19.6%；DAS28-4(CRP)结论：与背景风险研究一致，AEs在有CV风险的患者中更为常见，尤其是年龄≥65岁的患者。无论是否有冠心病风险，托法替尼的有效性/持久性基本相似。这些研究结果支持个体化治疗获益-风险评估，包括CV评估/管理，以优化RA预后。

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Tofacitinib Safety and Effectiveness in Canadian Patients with Rheumatoid Arthritis by Cardiovascular Risk Enrichment: Subanalysis of the CANTORAL Study.

Introduction: ORAL Surveillance, a post-authorisation safety study of patients with rheumatoid arthritis (RA) enriched for cardiovascular (CV) risk, demonstrated increased risk of major adverse CV events (MACE) and malignancies (excluding non-melanoma skin cancer [NMSC]) for tofacitinib versus tumour necrosis factor inhibitors (TNFi). This analysis of a real-world Canadian observational study evaluated tofacitinib safety/effectiveness in patients meeting or not meeting CV risk criteria.

Methods: CANTORAL included patients with moderate-to-severe RA initiating tofacitinib (10/2017-07/2020; N = 504). Interim data (data-cut: 07/2021) were stratified as CV risk-enriched (CV+ ; patients ≥ 50 years with ≥ 1 additional CV risk factor) or not CV risk-enriched (CV-; ≥ 50 years without additional CV risk factors and 18-49 years with/without CV risk factors). Safety and persistence were evaluated to month (M) 36. Effectiveness outcomes to M18 included Clinical Disease Activity Index (CDAI)-defined low disease activity (LDA)/remission (CANTORAL co-primary endpoints) and Disease Activity Score in 28 joints, C-reactive protein (DAS28-4[CRP]) < 3.2/ < 2.6.

Results: Overall, 272/232 patients were included in CV+ /CV- cohorts (full analysis set) (435/356 patient-years [safety analysis set]). Incidence rates (events/100 patient-years) in CV+ /CV- cohorts were 138.5/112.5 for treatment-emergent adverse events (AEs); 17.0/5.6 for serious AEs; 1.2/0.3 for deaths; 5.5/1.7 for serious infections; 1.4/1.1 for herpes zoster; 1.6/0.0 for MACE; 2.1/0.3 for malignancies (excluding NMSC); 0.7/0.6 for NMSC; 0.5/0.0 for venous thromboembolic events. Persistence was generally comparable between cohorts. In CV+ /CV- cohorts, at M6, CDAI LDA and remission rates were 51.5%/54.6% and 12.0%/19.6%; DAS28-4(CRP) < 3.2/ < 2.6 rates were 44.0%/39.3% and 31.5%/28.8%, respectively; effectiveness was generally maintained to M18.

Conclusions: In concordance with studies of background risk, AEs were more common in patients with CV risk enrichment, particularly those aged ≥ 65 years. Tofacitinib effectiveness/persistence were generally similar regardless of CV risk enrichment. These findings support individualised treatment benefit-risk assessment, including CV assessment/management, to optimise RA outcomes.

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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

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