抗TNF与DMARD治疗RA 缺血性卒中发生率相当

华盛顿——英国风湿病学会生物制剂注册-类风湿关节炎研究(BSRBR-RA)结果显示，与暴露于非生物性缓解病情抗风湿药物(nbDMARD)相比，暴露于抗肿瘤坏死因子(anti-TNF)药物并不增加类风湿关节炎(RA)患者的短期缺血性卒中风险。

英国曼彻斯特大学的Audrey S. Low博士在美国风湿病学会(ACR)年会上报告称，在这项大规模前瞻性RA患者队列研究中，共计确认130例缺血性脑血管意外患者，其中109例出现在anti-TNF药物治疗组(11,642例)，发病率为178/100,000例·年；21例发生于nbDMARD治疗组(3,271例)，发病率为175/100,000例·年，两组发病率未见显著差异。

采用倾向评分方法校正年龄、性别、种族、体重指数、疾病活动度评分、病程、健康评估问卷评分、既往nbDMARD应用情况、基线类固醇使用情况、入组年龄、吸烟、基线药物使用情况，以及癌症、高血压、缺血性心脏病、糖尿病、抑郁、慢性肺病等混淆因素后，也未见anti-TNF药物暴露与缺血性卒中风险之间存在关联[危险比(HR)，0.88]。

BSRBR-RA研究入组时间为2001~2008年，前3年每半年随访1次，然后每年随访1次，报告卒中等所有严重不良事件以及所有药物治疗情况，截止2010年10月21日的报告事件被纳入此次分析。研究者还将受试者情况与全国死亡注册与病例资料进行关联分析，力图对卒中类型进行分类。

两组受试者在以下几个方法存在差异：anti-TNF治疗队列年龄较低，女性较多，疾病活动性较强，病程较长且残疾程度较高。该队列应用DMARD、类固醇药物和非甾类环氧化酶-2(Cox-2)抑制剂也相对较多。但两组高血压和糖尿病发病率相似。

该研究是目前规模最大的表明anti-TNF与nbDMARD相比不增加RA患者卒中风险的研究之一。

研究者指出，其他多项观察性研究和Meta分析表明RA患者的卒中等心血管疾病发病率和死亡率增加，但有关anti-TNF药物治疗患者与对照患者的比较研究结果却不尽相同，某些研究显示缺血性卒中风险增加60%，而另一些研究则显示风险下降30%。

这项针对欧洲RA患者的大规模队列研究也再次表明，anti-TNF治疗的长期风险评估尚需进一步随访研究。

Low博士报告无相关利益冲突。

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By: SHARON WORCESTER, Cardiology News Digital Network

WASHINGTON – Exposure to anti-tumor necrosis factor therapy does not appear to be associated with a greater short-term risk of ischemic stroke in patients with rheumatoid arthritis when compared with exposure to nonbiologic disease-modifying antirheumatic drug therapy, according to findings from the British Society for Rheumatology Biologics Register-Rheumatoid Arthritis.

Of 130 verified incident ischemic cerebrovascular accidents that occurred among participants in that large prospective cohort study of RA patients, 109 occurred in 11,642 patients treated with anti–tumor necrosis factor drugs (anti-TNFs) for an incidence rate of 178/100,000 person-years, and 21 occurred in 3,271 patients in a comparator group of biologic-naive patients who had been treated with only nonbiologic disease-modifying antirheumatic drugs (nbDMARDs) for an incident rate of 175/100,000 person-years, Dr. Audrey S. Low reported at the annual meeting of the American College of Rheumatology.

The incident rates did not differ significantly, and no association was seen between ever exposure to anti-TNF drugs and ischemic stroke risk after adjustment for confounders using a propensity score based on age, sex, ethnicity, body mass index, disease activity score, disease duration, Health Assessment Questionnaire score, prior nbDMARD use, steroid use at baseline, year of entry to the study, smoking, baseline drugs, and history of cancer, hypertension, ischemic heart disease, diabetes, depression, and chronic lung disease (hazard ratio, 0.88), said Dr. Low of the University of Manchester (England).

Patients in the British Society for Rheumatology Biologics Register–Rheumatoid Arthritis (BSRBR-RA) were recruited during 2001-2008 and were followed semiannually for 3 years, then annually thereafter. All serious adverse events, such as stroke, and all drug therapy were reported. Events reported through Oct. 21, 2010, were included in this analysis.

The investigators also linked study subjects to the national death register and collected information from medical records; a concerted effort was made to classify stroke types.

The anti-TNF and nbDMARD groups differed with respect to several factors: The anti-TNF cohort was younger, included more women, and had higher disease activity, longer disease duration, and higher levels of disability. That cohort also used more DMARDs, more steroids, and more nonsteroidal cyclo-oxygenase-2 (COX-2) inhibitors. However, the rates of hypertension and diabetes were similar in the anti-TNF and nbDMARD cohorts.

This study is among the largest to show that anti-TNF therapy does not increase stroke risk in RA patients, when compared with nbDMARDS, Dr. Low said.

"We know that patients with RA are at risk of increased cardiovascular morbidity and mortality, and that includes stroke," she said, noting that several other observational studies and meta-analyses have demonstrated an overall increase in that risk.

However, outcomes have varied in studies comparing anti-TNF–treated RA patients and controls, with some showing as much as a 60% increase in ischemic stroke risk and others demonstrating a 30% reduction in risk.

In this large cohort of European patients with RA, no association was seen between the short-term risk of ischemic stroke and the use of anti-TNF therapy, she said, adding that additional follow-up is needed to assess risk over time.

Dr. Low reported having no relevant financial disclosures.