新数据催生新痛风指南

美国风湿病学会(ACR)发布的首部痛风治疗指南建议老药新用和调整预防策略。

这部指南包含两部分，9月28日发表在《关节炎治疗研究》杂志在线版上。加州大学洛杉矶分校风湿病学系执行主任John D. FitzGerald博士在接受采访时表示，该指南旨在促进痛风的有效治疗，使医生能将患者的尿酸水平降至6 mg/dl以下，从而改善其症状。“近年来在痛风治疗方面出现了相当多的新进展，包括别嘌呤醇和秋水仙碱的新替代药物，更安全地使用传统药物的新数据，等等。”据此，该指南在欧洲、荷兰和日本等国医学组织发布的指南的基础上作出了多项更新。

ACR指南的第一部分涵盖高尿酸血症的非药物治疗和药物治疗(Arthritis Care Res. 2012;64:1431-46 [doi:10.1002/acr.21772])。第二部分则聚焦于急性痛风性关节炎的预防和治疗(Arthritis Care Res. 2012;64:1447-61 [doi.wiley.com/10.1002/acr.21773])。

FitzGerald博士及另外2位共同主席——密歇根大学的Dinesh Khanna博士、加州大学圣迭戈分校的Robert Terkeltaub博士，对上世纪50年代以来的痛风相关医学文献进行了综述，继而描述了9种常见的临床情境。指南撰写组包含7位风湿病学家、2位初级保健医生、1位肾病专家和1位患者，由他们围绕上述情境拟定共识建议。

例如，关于别嘌呤醇的使用，撰写组建议从100 mg/d(而不是临床实践中常用的300 mg/d)的小剂量开始给药，对于合并慢性肾病的患者初始剂量甚至要更低，然后每2~5周增加1次剂量，逐渐达到靶剂量。这一建议支持此前美国食品药品管理局(FDA)和欧洲抗风湿病联盟(EULAR)的声明。

此外，在使用别嘌呤醇时必须进行严密监测和患者随访，以确保尿酸达标。“绝不能开完处方后就自认为任务完成了。这就跟给高血压患者开降压药一样，假如不追踪患者的血压，治疗效果就会大打折扣。”别嘌呤醇预防急性痛风发作的维持剂量可以超过300 mg，甚至对于合并慢性肾病的患者也是如此，不过前提是进行了充分的患者教育和监测。

新指南也降低了口服秋水仙碱治疗急性痛风发作的初始剂量，降至负荷量1.2 mg，1 h后服用0.6 mg，12 h后开始以每1~2天0.6 mg的剂量进行预防。“我们曾经将给药剂量提高到多达每天8片，但新数据显示增加秋水仙碱剂量实际上并不能改善结局，而且较小剂量更加安全，因此我们将发作初期的给药剂量降至3/4片。”作者将这一建议称为“一次范式转换”，从而与FDA批准的药品标签用语相一致。

新指南的其他要点包括：在别嘌呤醇严重不良反应风险高的患者中进行HLA-B*5801筛查的选择，当尿酸无法达标时的联合治疗，包括新药在内的药物选择，等等。

尽管这篇报告名为“指南”，但文中明确指出这些知识专家建议，临床医生应当主动、灵活地为特定患者选择最佳的治疗策略。撰写组并未对费用和成本效益进行评估，因此临床医生除了要考虑药物的疗效之外，还要考虑到其他诸方面因素。

ACR计划在获得更多新数据之后进一步更新这部指南。撰写组还提出了应用影像学检查的特定指征，原因是预计在今后数年内就会有针对痛风患者的高分辨率超声和双能CT研究结果问世。

据估计，美国约有4%(超过800万人)的成人患有痛风。FitzGerald博士表示：“我非常愿意将这些建议推荐给内科医生和家庭医生，因为如今他们遇到的痛风患者比风湿科医生遇到的还要多。”

FitzGerald博士无利益冲突披露。撰写组的若干成员报告称与多家药企有经济利益关系，不过大多数成员无潜在利益冲突。

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By: SHERRY BOSCHERT, Internal Medicine News Digital Network

The first guidelines on the management of gout from the American College of Rheumatology recommend new ways of using old drugs and changes in prophylaxis strategies, among other things.

The two-part guidelines, published online Sept. 28, should help speed up effective treatment of gout and get physicians to treat patients to a target urate level of less than 6 mg/dL in order to improve symptoms, Dr. John D. FitzGerald said in an interview.

"There has been a fair amount of recent movement on gout medications" including new alternatives to allopurinol and colchicine and new data on how to use those traditional drugs in safer ways, said Dr. FitzGerald, acting chief of the rheumatology division at the University of California, Los Angeles. "It’s a fair number of changes for medications that people had been using for decades."

The documents update previous guidelines from medical organizations in Europe, the Netherlands, and Japan. The new guidelines will be published in October 2012 by the journal Arthritis Care & Research.

Part 1 of the American College of Rheumatology (ACR) guidelines covers nonpharmacologic and pharmacologic approaches to managing hyperuricemia (Arthritis Care Res. 2012;64:1431-46 [doi:10.1002/acr.21772]).

Part 2 addresses prophylaxis and treatment for acute gouty arthritis (Arthritis Care Res. 2012;64:1447-61 [doi.wiley.com/10.1002/acr.21773]).

Dr. FitzGerald and two other co-leaders of the project, Dr. Dinesh Khanna of the University of Michigan, Ann Arbor and Dr. Robert Terkeltaub of the University of California, San Diego, reviewed the medical literature on gout from the 1950s to the present and drew up nine clinical case scenarios commonly seen in practice. A task force panel comprising seven rheumatologists, two primary care physicians, a nephrologist, and a patient representative used the scenarios to create consensus recommendations.

Among the recommendations, for example, on the use of allopurinol is to start at a low dose of 100 mg/day (instead of the common practice of starting with 300 mg/day), or even lower for patients with chronic kidney disease, and then gradually titrate upward every 2-5 weeks. That recommendation supports previous statements from the Food and Drug Administration and the European League Against Rheumatism.

Also, allopurinol therapy should be actively managed and patients followed to make sure the uric acid target is achieved. "You can’t just give a prescription and say your job is done," though some recent studies suggest that many physicians do just that, Dr. FitzGerald said. "The corollary would be if someone gave blood pressure medication and then didn’t follow the patient’s blood pressure. That wouldn’t be seen as good medicine."

Maintenance doses of allopurinol to prevent acute gout attacks can exceed 300 mg even in patients with chronic kidney disease provided there is adequate patient education and monitoring.

A new recommendation drops the starting dose of oral colchicine for acute gout attacks to a loading dose of 1.2 mg, followed by 0.6 mg an hour later, and then starting prophylaxis 12 hours later at dosing of 0.6 mg once or twice daily.

"We used to give up to eight tablets a day," Dr. FitzGerald said. "That is dropped down to three to four tablets at the start of an attacks, because of findings that more colchicine didn’t really help outcomes" and that smaller doses are safer. The authors called this recommendation from ACR "a paradigm shift" that’s in accordance with Food and Drug Administration-approved label language.

Other highlights of the new ACR recommendations include sections on screening for HLA-B*5801 in patients at high risk of severe adverse reaction to allopurinol, combination therapy when target urate levels are not achieved, medication options including new drugs, and more.

Although the reports are titled "Guidelines," the text makes clear that they are expert recommendations and that clinicians are expected to take active roles in choosing the best management strategies for their particular patients. The authors were "very concerned" that the guidelines not be used by third-party payers to restrict access to medications or to promote one drug over another if there isn’t clear evidence to support it, Dr. FitzGerald said.

The methodology of the project precluded evaluations of costs and cost effectiveness, instead focusing on efficacy. So, for example, the guidelines say that allopurinol and febuxostat can be used equivalently in some circumstances, but clinicians need to consider all other aspects of these options including cost, patient preference, and more.

The ACR plans to update the guidelines as new data become available. The task force panel did create specific indications for use of imaging studies because results should be available in the next few years from studies on the use of high-resolution ultrasound and dual-energy CT for patients with gout.

In the United States, gout affects an estimated 4% of adults – more than 8 million people.

"I’m most excited and hopeful about trying to get this out to internal medicine and family practice doctors," Dr. FitzGerald said. "They see more gout than rheumatologists."

Dr. FitzGerald reported having no financial disclosures. Some members of the task force reported financial associations with multiple pharmaceutical companies but, by design, a majority of task force members had no perceived potential conflicts of interest.