雷公藤多甙治疗类风湿关节炎遭质疑

    MedPage Today于2014年6月20发布了其职员Nacy Walsh所写以下报道。

    在中国有着悠久历史的雷公藤治疗类风湿关节炎（RA）的疗效得到一项为期24的随机对照研究的证实。但是有学者（唐纳德·马库斯，休斯顿贝勒医学院的一位教授）写信给风湿病领域学术期刊（Ann Rheum Dis）提出质疑，24周观察期太短。中国悠久使用历史也未确立雷公藤的安全性，并认为该研究的相关人员关于可能适用于绝经后妇女的建议是不完善的，因为还未考虑到雌激素长期低水平对绝经后妇女骨代谢、心血管安全性以及认知功能的影响。

    马库斯教授提到近期在台湾完成的一项研究表明, 约三分之一的人使用过含马兜铃（Aristolochia）的中草药，可能面临者肾功能不全以及泌尿系统肿瘤的发生风险。纽约石溪大学亚瑟·格罗曼在论文中称，马兜铃酸的肾毒性是不可逆的，它的致癌性要在长期使用30年后才会表现出来。格罗曼的研究显示，台湾60%的上尿路肿瘤患者可检测到马兜铃酸结合DNA所形成的加合物, 以及PF53抑癌基因特征性的突变，从而支持关于马兜铃酸可能导致泌尿道上皮癌的假说。

    马库斯教授建议，尽管雷公藤短期免疫抑制和抗炎特性与诸如甲氨蝶呤等传统DMARDs的单药疗效相似，在没有获知长期疗效和安全性之前，目前仍不能将雷公藤视为RA传统化药的一种“安全替代品”。

原文和网址如下。

http://www.medpagetoday.com/Rheumatology/Arthritis/46427

Rheuminations: Chinese Herb for RA Questioned

Published: Jun 20, 2014

By Nancy Walsh, Senior Staff Writer, MedPage Today

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We recently reported on a randomized study conducted in China in which a plant extract widely used in traditional Chinese medicine was found to be noninferior to methotrexate in patients with rheumatoid arthritis (RA), and had similar rates of adverse events as the drug.

But not everyone agrees that the herbal extract is safe.

In the Chinese study, which was published in Annals of the Rheumatic Diseases, 55.1% of patients receiving extracts of Tripterygium wilfordii Hook F had improved by 50% by 6 months, as had 46.4% of those given methotrexate, and 76.8% of patients using both.

The investigators, led by Xuan Zhang, MD, of the Chinese Academy of Medical Sciences in Beijing, reported that the herbal treatment improved disease activity, pain, tender and swollen joints, erythrocyte sedimentation rate, and patient assessment of function.

The most common adverse events were gastrointestinal, occurring in 29% of patients takingT. wilfordii, in 34.8% of those taking the plant extract plus methotrexate, and in 43.5% of those on methotrexate monotherapy.

Several female patients also developed menstrual irregularities, which is a recognized side effect of the herbal medication, and Zhang and colleagues suggested that the treatment "should be used in postmenopausal female patients and in patients who are no longer interested in having children."

But a letter to the editor just published in the Annals has raised notable safety concerns withT. wilfordii -- and Chinese herbal medicine in general.

"The history of long-term use in China does not establish the safety of [T. wilfordii]," wroteDonald M. Marcus, MD, who is professor emeritus at Baylor College of Medicine in Houston.

Among the points Marcus makes in his letter are that the duration of the study -- 24 weeks -- was too short to evaluate the safety of a treatment that is likely to be needed for years.

He also objects to the authors' suggestion that the treatment could be suitable for postmenopausal women, stating, "they do not consider the consequences of a long-term decrease in estradiol, which include osteoporosis, fractures, and possibly cardiovascular and cognitive problems."

In addition, the treatment can lead to impairments in renal function.

Finally, Marcus pointed out that in Chinese herbal medicine, extracts from other plants, specifically those of the Aristolochia species, have been used for hundreds of years and remain popular, despite their known nephrotoxicity.

He referenced a study conducted in Taiwan by Arthur P. Grollman, MD, of Stony Brook University in New York, who noted that more than 100 years ago, extracts derived from A. clematitis were shown to be nephrotoxic in animals.

Grollman's study found that about one-third of the Taiwanese population may have used herbal medicines containing Aristolochia and therefore may be at risk for renal insufficiency and urothelial cancer.

"Importantly, the nephrotoxic effects of [aristolochic acid] are irreversible and its carcinogenic effects may not become manifest until 30 or more years after exposure,"Grollman wrote in Environmental and Molecular Mutagenesis.

"The role of aristolochic acids in causing urothelial carcinoma was confirmed by the finding that 60% of upper urinary tract tumors in Taiwan contained aristolochic acid-DNA adducts and signature mutations in the PF53 tumor suppressor gene," Marcus explained.

While the short-term immunosuppressive and anti-inflammatory properties of T. wilfordiimay be similar to those of methotrexate, this herb shouldn't be thought of as a "safe alternative" for patients with RA until much more is known about long-term effects, according to Marcus.

"Although [T. wilfordii Hook F] is approved for use in China, it should be considered an experimental therapy whose safety requires further study," Marcus concluded.

Rheuminations is a blog by Nancy Walsh for readers with an interest in rheumatology.

Marcus disclosed no relevant relationships with industry.

 

Primary source: Annals of the Rheumatic Diseases
Source reference: Marcus D "Comparison of Tripterygium wilfordii Hook F with methotrexate in the treatment of rheumatoid arthritis" Ann Rheum Dis 2014; DOI: 10.1136/annrheumdis-2014-205971.