OARSI发布新版膝骨关节炎指南

国际骨关节炎研究学会(OARSI)发布的新版膝骨关节炎指南(前一版本于2010年发布)提出了减重、教育和锻炼等建议，与近年来发布的美国风湿病学会(ACR)指南和美国整形外科医师协会(AAOS)指南有较大区别(Osteoarthritis Cartilage 2014 Jan. 23 [doi:10.1016/j.joca.2014.01.003])。

例如，AAOS的2013年指南对于皮质类固醇和对乙酰氨基酚膝部注射剂持折中态度，指出缺乏证据；而OARSI指南建议在没有相关合并症的情况下使用这两种药物。近期有关类固醇膝部注射剂的研究显示，此类药物可带来临床显著的短期疼痛缓解，显著优于关节内注射透明质酸。

同时，透明质酸膝部注射剂在另一项研究中提供了更长时间的缓解，这一发现使得OARSI提出了与ACR相似的建议，将透明质酸膝部注射剂列为“不明确”。AAOS反对使用透明质酸，认为该药缺乏疗效。

OARSI的建议是基于近期文献和13人评审委员会的专家意见；多数委员是风湿病学家且多数来自欧洲。委员会对13项非药物治疗和16项药物治疗进行了投票，将其分为“适用”、“不适用”或对膝骨关节炎价值“不明确”(当缺乏证据时)。

被判定为对所有膝骨关节炎患者都“适用”的治疗方法包括生物力学干预、皮质类固醇膝部注射剂、地面和水中锻炼、自我管理和教育、力量训练和体重管理。其他获得委员会认可的治疗方法包括对乙酰氨基酚、浴疗(采用富含矿物质的热水)、局部使用辣椒素、步行手杖、度洛西汀(欣百达)，以及在没有禁忌证的情况下是使用NSAID。

多种治疗方法被判定为“不确定”：针灸、鳄梨-大豆提取物补充剂、软骨素、拐杖、双醋瑞因、葡糖胺、关节内注射透明质酸、阿片类、野玫瑰果、经皮神经电刺激和治疗性超声。由于缺乏证据，委员会将利塞膦酸钠(Actonel)和神经肌肉电刺激判定为“不适用”于膝骨关节炎。

作者指出，更近期的研究结果已“加剧了对运用诸如对乙酰氨基酚和阿片类之类治疗的安全性担忧，与此同时，支持使用诸如度洛西汀、浴疗法和地面运动(如太极拳)的证据正在加强”。

OARSI比其他组织更加支持生物力学干预，主要原因是当前研究提示膝部角撑和足部矫形器可改善功能，减少疼痛、僵直和药物使用。另一项试验支持用楔形鞋垫作为外翻足支撑的替代品。

与ACR指南相似，而与AAOS的更强烈建议不同的是，OARSI也支持多数患者口服NSAID，但不确定患有心脏病和其他相关问题的患者是否也应口服NSAID。OARSI建议在担心胃出血的情况下伴随使用质子泵抑制剂。

他们指出，萘普生在心血管系统安全性方面似乎优于COX-2抑制剂。双氯芬酸似乎有更高几率发生肝酶异常，而塞来昔布(西乐葆)似乎较少引起溃疡但较多引起心血管问题。局部NSAID对于膝骨关节炎疼痛的疗效与口服剂型相当而问题更少。

与ACR不同的是，OARSI还认为局部辣椒素“适用于无相关合并症的患者”，度洛西汀“适用于多数临床亚型”，尽管不良事件——恶心、疲乏和其他——和“更具靶向性的治疗的可供选择，意味着对仅有膝部受累的骨关节炎且有合并症的患者的适用性存在不确定性”。

OARSI资助了指南编撰工作，并获得了关节炎产品生产商的支持。多数评审委员与赛诺菲、辉瑞、默克、Don-Joy等公司有关联，但主动要求在必要时不参与投票。

专家点评

OARSI并未详述各种疗法在联用时如何发挥作用。这是所有指南的通病。关于联合治疗的文献非常有限，因此指南只能考虑单独使用这些疗法，然而实际上联合治疗是风湿病学临床的惯常做法。

OARSI指南在很大程度上收到了欧洲同行的影响。这并不是坏事，但美国风湿科医生治疗患者的方式并不总是与欧洲同行一样。例如双醋瑞因并未在美国上市，鳄梨补充剂也不流行。

此外，OARSI并未将硫酸葡糖胺和盐酸葡糖胺分开描述。盐酸葡糖胺显然是无效的，至于硫酸葡糖胺是否有效，文献中尚未得出一致结论。我也不确定是否应当将所有关节内透明质酸一概而论，或许它们之间是存在差异的。

一般来说，指南的影响不大。目前已有太多指南可供临床医生依循，而且有时候这些指南之间是矛盾的。

点评专家Roy Altman医生是加州大学洛杉矶分校风湿病学教授。他参与了Ferring、辉瑞等公司的关节炎研究项目，并且是《风湿病学新闻》的编委会成员。他还是2012年美国风湿病学会《手、膝与髋骨关节炎指南》的作者之一。

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By: M. ALEXANDER OTTO, Internal Medicine News Digital Network

New knee osteoarthritis guidelines from Osteoarthritis Research Society International, an update of the group’s 2010 guidelines, recommend weight loss, education, exercise, and much more that’s familiar to practicing rheumatologists.

However, the group’s advice varies a bit from recent osteoarthritis (OA) guidelines separately issued by the American College of Rheumatology (ACR) and the American Academy of Orthopaedic Surgeons (AAOS).

For instance, the AAOS was neutral on acetaminophen and corticosteroid knee shots in its 2013 recommendations, citing a lack of evidence, but Osteoarthritis Research Society International (OARSI) guidelines recommend both in the absence of relevant comorbidities. Recent studies of steroid knee shots demonstrate "clinically significant short-term decreases in pain" that are "significantly greater" than are those with intra-articular hyaluronic acid, according to guidelines lead author Dr. Timothy McAlindon, chief of rheumatology at Tufts University in Boston, and his colleagues (Osteoarthritis Cartilage 2014 Jan. 23 [doi:10.1016/j.joca.2014.01.003]).

Meanwhile, hyaluronic acid knee injections provided greater long-term relief in another study, one of the findings that led OARSI, like the ACR, to suggest that the jury’s still out on hyaluronic acid. The AAOS rejected hyaluronic acid because of a lack of efficacy.

OARSI’s advice is based on recent literature and the expert opinion of its 13-member review panel; most members were rheumatologists and most were European. They voted on 13 nonpharmaceutical and 16 pharmaceutical treatments, deciding if they were appropriate, inappropriate, or – when evidence was scanty – of uncertain value for knee OA.

Treatments that made the cut as appropriate for all knee OA patients included biomechanical interventions, corticosteroid knee injections, land and water-based exercise, self-management and education, strength training, and weight management. Other treatments approved by the panelists included acetaminophen, warm soaks in mineral-rich water (balneotherapy), topical capsaicin, walking canes, duloxetine (Cymbalta), and NSAIDs when comorbidities don’t rule them out.

A variety of therapies fell into the "uncertain" category: acupuncture, avocado-soybean unsaponfiable supplements, chondroitin, crutches, diacerein, glucosamine, intra-articular hyaluronic acid, opioids, rose hip, transcutaneous electrical nerve stimulation, and therapeutic ultrasound. The group voted risedronate (Actonel) and neuromuscular electrical stimulation as inappropriate for knee OA because of a lack of evidence.

Newer findings have "increased safety concerns regarding use of treatments such as acetaminophen and opioids ... while evidence for use of treatments such as duloxetine, balneotherapy, and land-based exercises such as t’ai chi has strengthened," the authors noted.

OARSI reviewed biomechanical interventions more favorably than did the other groups, mostly because research now suggests that knee braces and foot orthoses improve function and decrease pain, stiffness, and drug use. Another trial supported wedged insoles as an alternative to valgus bracing.

Similar to the ACR guidelines but unlike stronger recommendations from the AAOS, OARSI also supported oral NSAIDs for most patients but was unsure about them when patients have heart disease and other relevant problems. The group recommended concomitant proton-pump inhibitors when gastric bleeding is a worry.

They noted that naproxen seems safer on the cardiovascular system than COX-2 inhibitors. Diclofenac appears to carry the highest risk for abnormal liver values, while celecoxib (Celebrex) seems to cause fewer ulcers but more cardiovascular problems. Topical NSAIDs work as well as oral formulations for OA knee pain, with fewer problems.

Unlike the ACR, the group also considered topical capsaicin "appropriate in patients without relevant comorbidities" and duloxetine "appropriate for most clinical subphenotypes," although adverse events – nausea, fatigue, and others – and the "availability of more targeted therapies predicated uncertain appropriateness for individuals with knee-only OA and comorbidities," they said.

OARSI funded the work, and is supported by companies promoting arthritis products. Most of the panelists have financial ties to Sanofi, Pfizer, Merck, Don-Joy, and other companies, but recused themselves when needed from voting.

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Lack of multimodal therapy guidance

OARSI didn’t tell us a lot about how treatments work in combination. That’s a major fault with all the guidelines. There’s very little literature on multimodal therapy, so guidelines consider treatments in isolation, whereas in rheumatology, we combine treatments.

OARSI’s guidelines were also very much influenced by Europeans. That’s not a bad thing, but in the United States, we don’t always treat people the same way as they do in Europe. Diacerein isn’t available here, and avocado-soy unsaponfiables aren’t popular.

Dr. Roy D Altman

Also, OARSI doesn’t separate glucosamine sulfate from glucosamine hydrochloride. Glucosamine HCl clearly is not effective, but the literature has some confusion about whether glucosamine sulfate works. I’m also not sure it’s appropriate to lump all the intra-articular hyaluronics together; there may be differences among them.

Guidelines, in general, have minimal impact. There are too many for practicing physicians to track, and sometimes they contradict each other.

Dr. Roy Altman is a professor of medicine in the division of rheumatology at the University of California, Los Angeles. He works with Ferring, Pfizer, Novartis, and other companies on arthritis research projects, and is an editorial advisory board member of RHEUMATOLOGY NEWS. He was also an author of the 2012 American College of Rheumatology hand, knee, and hip OA guidelines.