背景:在口腔监测中,在心血管(CV)风险高的类风湿关节炎(RA)患者中,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])的发生率(IR)在北美使用托法替尼的数值上高于世界其他地区。由于潜在的风险因素。这里,我们评估了托法替尼与肿瘤坏死因子抑制剂(TNFi)在不同地区RA患者中的安全性和有效性.
方法:RA患者的口腔监测(NCT02092467),年龄≥50岁,有≥1个附加CV危险因素的人,服用托法替尼5或10mg,每日2次或TNFi;45.9%来自波兰或北美.这项事后分析按地区对患者进行了分层(波兰,北美,其他国家)。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,与C反应蛋白(DAS28-4[CRP]),健康评估问卷-残疾指数(HAQ-DI)。报告了不良事件的IRs和风险比。
结果:4362例患者(波兰,N=759;北美,N=1243;其他国家,N=2360),与波兰/其他国家/地区相比,来自北美的更多患者有CV危险因素,如体重指数≥30kg/m2和糖尿病/高血压病史;然而,与其他地区相比,来自波兰的更多患者曾吸烟,与其他国家相比,来自波兰/北美的更多患者有冠状动脉疾病史.MACEIR在北美和波兰相似,与其他国家相比,数字更高。与使用托法替尼的波兰/其他国家相比,北美的恶性肿瘤(不包括NMSC)的IR在数字上较高。在各种治疗中,北美的严重感染IR在数字上高于波兰。静脉血栓栓塞/全因死亡率IRs在不同地区通常具有可比性。DAS28-4(CRP)/HAQ-DI改善在北美通常最低。
结论:安全性结果的差异是由基线危险因素的存在驱动的;与其他国家相比,北美和波兰显示出具有某些基线CV危险因素/合并症的患者比例更高。
背景:NCT02092467(ClinicalTrials.gov)。
BACKGROUND: 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.
BACKGROUND: NCT02092467 (ClinicalTrials.gov).