SANTA MONICA, California (EGMN) – Treatment of rheumatoid arthritis has undergone a sea change, word of which has not reached beyond rheumatology in many cases.

Primary among the new rules of RA care is the admonition to use the best drug first and that overtreatment is good. Physicians should move more quickly to using combinations of agents, because “data show we undertreat,” said Dr. John J. Cush, director of clinical rheumatology for the Baylor Research Institute and professor of medicine and rheumatology at Baylor University Medical Center at Dallas.

In addition to aggressive use of disease-modifying antirheumatic drugs (DMARDs), the optimal treatment of RA requires that rheumatologists seize the opportunity to diagnose and manage cases of early disease. Numerous measures can be adopted to ensure the rheumatologist’s role in this effort, but Dr. Cush specifically advocates for the “promotion of practice policies to facilitate referral and [ensure] that every patient seeking an appointment for joint pain should be seen within 2 week or sooner.”

The integration of disease activity metrics can enhance outcomes by guiding treatment changes to achieve a specific goal. “Use of metrics yields a fourfold increase in remission rates,” Dr. Cush said at a meeting sponsored by Rheumatology News and Skin Disease Education Foundation.

Word of the negative impact of comorbidities in RA has not spread far beyond rheumatology to primary care specialties. Given the cardiovascular disease (CVD) risks alone, physicians need to identify and treat comorbidities in this population, he said.

RA is not just a joint disease. Affected patients develop CVD 10 years earlier than their unaffected peers, they have twice the malignancy rate of the general population, their rate of serious infection is six to nine times that of the general population, and their risk for both pulmonary disease and gastrointestinal bleeding is elevated. As a result, the life expectancy of RA patients is shorter than that of their age-matched peers (10 years shorter for women and 4 years shorter for men).

Data from the Mayo Clinic in Rochester, Minnesota, however, show that survival has improved significantly over the past decade. Research presented at the 2009 annual meeting of the American College of Rheumatology, but not yet published, indicated that survival was 70.7% among 147 RA patients who were followed in 1955-1994. In 1995-2007, survival increased to 79.5% in a group of 463 RA patients. Both patient groups were from the Olmsted County, Minnesota, cohort.

Earlier diagnosis and the use of methotrexate and biologic DMARDs may have contributed to this finding, he said.

Although many are enamored with the potential benefits of new biologics, rheumatologists should remain resolute in their use of methotrexate, according to Dr. Cush. Findings from a recent meta-analysis suggest that the optimal methotrexate dosage may be achieved by starting at 15 mg/wk orally, then escalating by 5 mg/month to a maximum dosage of 25-30 mg/wk or the highest tolerable dose. In cases of insufficient response, the route of administration can be switched from oral to subcutaneous administration (Ann. Rheum. Dis. 2009;68:1094-9).

Several studies have compared methotrexate vs. tumor necrosis factor inhibitors with regard to efficacy and x-ray–protective effects. Methotrexate appears to be as potent as TNF inhibitors in terms of clinical outcomes. When x-ray outcomes are analyzed, however, the biologic has a margin of benefit over methotrexate that becomes more pronounced when the TNF inhibitor is combined with methotrexate.

Other data have documented the cost-effectiveness of therapy in early RA. Very early DMARD therapy is cost effective in reducing RA progression, but the cost-effectiveness of early biologics remains uncertain (Ann. Intern. Med. 2009;151:612-21).

When methotrexate monotherapy does not produce enough benefit, the recommended course is to add a biologic DMARD, usually a TNF inhibitor. The top five indications for the use of a TNF blocker in rheumatology are failure of methotrexate monotherapy, failure of multiple DMARDs, physician assessment of activity, presence of erosions on x-rays, and functional disability.

There remains room for improvement in RA therapy. “Despite improved responses with current approaches, a remission response is not seen in many,” said Dr. Cush. In addition, biologic DMARDs are beset by associated adverse events, high costs, and the need for improved production and administration technology. The next generation of agents should also lessen comorbidities and improve patients’ likelihood of remission and achievement of a low-disease state.

Dr. Cush reported being a clinical investigator, advisor, or consultant for numerous pharmaceutical companies.

SDEF and this news organization are owned by Elsevier.

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加利福尼亚州圣莫尼卡(EGMN)——类风湿性关节炎(RA)的治疗有了重大改变，但在多数情况下，治疗并未超出风湿病学范畴。

 

类风湿性关节炎新的治疗原则建议首先使用最好的药物，提倡过度治疗。医生应该迅速改变观念，采用药物联合治疗，因为“资料显示我们现有的治疗不充分，”达拉斯的贝勒研究所临床风湿病学主任和贝勒大学医学中心内科学和风湿病学教授John J. Cush博士说道。

 

除了积极采用改善病情的抗风湿药物(DMARD)，治疗类风湿性关节炎最好的方法要求风湿病学家抓住早期诊断和早期治疗的机会。风湿病学家可以采用很多方法努力做到尽早诊断、尽早治疗，Cush博士特别提倡“改进医疗政策，方便转诊，确保患关节疼痛的每名患者都应该在2周内或更短的时间内就诊。”

 

疾病活动指标可用于指导治疗，达到特定目标，从而提高疗效。“使用疾病活动指标能使缓解率增至4倍，”Cush博士在风湿病学新闻和皮肤病教育基金会主办的一次会议上说道。

 

类风湿性关节炎合并疾病负面影响的有关知识仅为风湿病学家知晓，初级保健医生还不太了解。倘若存在单一心血管疾病风险，医生需要在该人群中进行识别，处理合并疾病，他说到。

 

类风湿性关节炎不只是关节疾病。受累患者患心血管疾病比未受累的同等人群早10年，他们患恶性肿瘤的几率是普通人群的两倍，患严重感染的几率是普通人群的6~9倍，患肺部疾病和胃肠道出血的几率也增高。因此，类风湿性关节炎患者的预期寿命短于年龄相近的同类人群(女性少10年，男性少4年)。

 

然而，明尼苏达州罗彻斯特Mayo医院的资料显示，在过去10年里，生存率已显著提高。美国风湿病学会2009年会的一项研究报告，147名类风湿性关节炎患者的生存率为70.7%，随访期为1955~1994年。1995~2007年，463名类风湿性关节炎患者的生存率提高至79.5%。这两个患者组均来自明尼苏达州奥姆斯特德县。

 

这一结果可能归功于早期诊断、采用甲氨喋呤和生物制剂DMARD治疗。

 

尽管多数人倾心于新的生物制剂的潜在益处，风湿病学家仍然应该坚持采用甲氨蝶呤，Cush博士认为。一项最新的荟萃分析提示，甲氨蝶呤最佳剂量为开始时每周口服15 mg，之后每月增加5 mg，最大剂量为每周25~30 mg，或者采用最大耐受剂量。疗效不佳者，用药途径可以从口服改为皮下注射(Ann. Rheum. Dis. 2009;68:1094-9)。

 

一些研究比较了甲氨蝶呤和肿瘤坏死因子抑制剂的疗效和X线证实的保护作用。在临床疗效方面，甲氨蝶呤与肿瘤坏死因子抑制剂一样有效。然而，分析X线证实的结果时，生物学制剂稍优于甲氨蝶呤，肿瘤坏死因子抑制剂联合甲氨蝶呤时，效果更加显著。

 

其他数据也证明了类风湿性关节炎早期治疗的成本效益。很早期的DMARD治疗在抑制类风湿性关节炎进展方面经济有效，但是早期采用生物制剂的成本效益仍不确定(Ann. Intern. Med. 2009;151:612-21)。

 

采用甲氨蝶呤单一治疗并不能产生足够好的收益，建议联合应用生物制剂DMARD，通常采用肿瘤坏死因子抑制剂。风湿病学领域采用肿瘤坏死因子抑制剂的前5种适应证为甲氨蝶呤单一治疗无效、多种DMARD无效、医生评价疾病活动度、X线摄影出现侵蚀，以及功能障碍。

 

类风湿性关节炎治疗仍能够得到改进。“尽管目前治疗方法的疗效获得改善，但疾病缓解的患者还不太多，”Cush博士说。另外，生物制剂DMARD存在相关不良事件、花费高、需要提高产品和用药技术等缺陷。下一代制剂应该减轻并发疾病，提高患者缓解的可能性，并达到疾病低度活动状态。

 

Cush博士报告担当多家制药公司的临床研究者、顾问。

 

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