2012年ACR痛风指南解读与安康信的应用
2012年美国风湿病学会痛风治疗指南解读
的，在T 2相上大部分是中等信号，少数为高信号，并且造影后呈现明显的强化。
这种强化可能和组织学上看到的周围“纤维血管区”中占优势的血管成比例。
在T 2加权像上的低信号点倾向于钙化灶。
6痛风、其他结晶性关节病和感染的影像学区别临床上，痛风的表现可以和感染性关节炎相似，包括发热，关节红肿热痛，血白细胞计数增多，血沉、C 反应蛋白升高；但痛风骨侵蚀的典型表现，易发作部位及缺乏邻近软组织化脓，有助于痛风诊断的征象。
抽取关节腔积液在偏振光显微镜见绿色针样晶体，革兰染色为阴性，将有助于痛风诊断。
关节软骨表面的MSU 结晶沉积物在超声中表现平行于骨皮质的回波曲线带，形成“双轨征”。
这是和焦磷酸钙结晶疾病有明显区别的征象，焦磷酸盐沉积症通常导致结晶沉积在关节内而不是关节表面。
超声为能检查出这些区别的最敏感的方式。
7影像学监测治疗效果随着更多新型、有效降尿酸方法的出现，人们尝试用影像学手段监测治疗疗效。
影像学变化包括痛风石的缩小、“双轨征”的消失、滑膜增生停止、关节渗出和骨髓水肿的改善。
CT 和MRI 采用先进的痛风石3D 绘图，使CT 和MRI 描述病变更加准确和逼真。
DECT 基于化学成分能识别尿酸结晶，在治疗随访中，观察溶解的痛风石方面更确切、可靠。
MRI 在随访滑膜增生和骨髓水肿方面有它特殊的价值，而超声是可以显示上述（除骨髓水肿外）所有影像表现的一种极好的廉价的方法，从而可以替代评估方法，并能提供精确的细节和良好的空间分辨率。
尽管MRI 在临床和科研方面同样有助于监测疾病进展，但随访不便捷且花费高。
因此，超声有望成为监测治疗反应的最佳方法。
综上所述，长期以来，影像学在诊断和随访痛风疗效方面价值十分有限，随着影像学技术的发展和临床案例探索，超声可用来指导穿刺获得组织样本，甚至在深部组织中寻找尿酸沉积物，从而有助于诊断。
准确地评估痛风的疾病活动性，并能有助于非典型急性痛风及伴痛风石的慢性痛风的诊断，同时评估治疗反应。
安康信(依托考昔片)使用说明
安康信(依托考昔片)【用法用量】本品用于口服，可与食物同服或单独服用。
急性痛风性关节炎-推荐剂量为120毫克，每日1次。
本品120毫克只适用于症状急性发作期，最长使用8天。
使用剂量大于推荐剂量时，尚未证实有更好的疗效或目前尚未研究。
因此，上述剂量是最大推荐剂量。
因为选择性环氧化酶-2抑制剂的心血管危险性会随剂量升高和用药时间延长而增加，所以应尽可能减短用药时间和使用每日最低有效剂量。
应定期评估患者症状的缓解情况和患者对治疗的反应。
【注意事项】临床试验提示相比于安慰剂和一些非甾体抗炎药（萘普生），选择性环氧化酶－2抑制剂发生血栓事件（尤其是心肌梗塞和中风）的危险性增加。
因为选择性环氧化酶－2抑制剂的心血管危险性可能会随剂量升高和用药时间延长而增加，所以应尽可能缩短用药时间和使用每日最低有效剂量。
应定期评估患者症状的缓解情况和患者对治疗的反应。
对于有明显的心血管事件危险因素（如高血压﹑高血脂﹑糖尿病﹑吸烟）或末梢动脉病的患者,在接受本品治疗前应经过谨慎评估。
即使既往没有心血管症状，医生和患者也应对此类事件的发生保持警惕。
应告知患者严重心血管安全性的症状和/或体征以及如果发生应采取的步骤。
患者应该警惕诸如胸痛﹑气短﹑无力﹑言语含糊等症状和体征，而且当有任何上述症状或体征发生后应该马上寻求医生帮助。
因为选择性环氧化酶－2抑制剂对血小板不具有作用,因此不可以此类药物替代阿司匹林用于预防心血管疾病。
本品是此类药物中的一种，并不能抑制血小板凝集，所以不能停止抗血小板治疗。
避免与其它任何非甾体抗炎药或者阿司匹林合并用药。
当依托考昔﹑其他选择性环氧化酶－2抑制剂和非甾体抗炎药与阿司匹林（即使是低剂量）合用时，发生胃肠道不良事件（胃肠道溃疡或其他胃肠道并发症）的危险性增高。
目前尚未有长期临床试验充分评估比较选择性环氧化酶－2抑制剂与阿司匹林合用和非甾体抗炎药与阿司匹林合用对胃肠道安全性差异。
对晚期肾脏疾病患者，不推荐用本品治疗。
骨科精读老年难治性痛风用药细则，一文读懂！
骨科精读老年难治性痛风用药细则，一文读懂！高尿酸血症（HUA）是指在正常嘌呤饮食状态下，非同日2次空腹血尿酸水平男性>420μmol/L，女性>360μmol/L。
痛风与嘌呤代谢紊乱或尿酸排泄减少所致的HUA直接相关，是一种单钠尿酸盐沉积所致的晶体相关性关节病，属代谢性风湿病的范畴，为代谢综合征、糖尿病、血脂异常、心血管疾病、慢性肾脏病（CKD）和脑卒中等疾病发生的独立危险因素。
难治性痛风（RCG）是指急性痛风性关节炎反复发作数年后，出现慢性多发性、破坏性关节炎，伴痛风石形成和（或）尿酸性肾结石，常规剂量降尿酸药物难以使血尿酸达标的痛风，常表现为关节持续肿胀、疼痛、多发性痛风石和关节破坏等。
难治性痛风存在以下3条中至少1条情况，即单用或联用常规降尿酸药物足量、足疗程，但血尿酸仍≥360μmol/L；接受规范化治疗，痛风仍发作≥2次/年；存在多发性和/进展性痛风石。
《中国高尿酸血症与痛风诊疗指南（2019）》中指出，近年来多项难治性痛风的临床研究将基线血尿酸≥480μmol/L，且存在下列临床特征中的至少一条定义为难治性痛风，即在过去18个月，痛风发作3次以上；至少1个痛风石；持续性关节疼痛或影像学显示痛风相关的关节损伤；别嘌醇有禁忌，或使用最大剂量治疗3个月以上时血尿酸仍不达标者。
2012年美国风湿病学会（ACR）提出有以下临床特征之一即可定义为难治性痛风，即血尿酸难以达标；有持续的痛风相关临床表现（反复痛风发作、慢性痛风性关节炎、痛风石形成、尿酸性肾结石）。
年龄是HUA的独立危险因素，且老年患者因体力活动减少、代谢减慢、高嘌呤饮食、肥胖等可致痛风发生。
同时，老年患者共病多，常合并高血压（降压药物如氢氯噻嗪、β受体阻断剂可增加继发性高尿酸血症和痛风发生的风险）、糖尿病、高脂血症、慢性肾脏病（CKD）、冠心病（CAD）等疾病，还有基础肾功能差、肾脏排泄能力下降、多重用药（影响降尿酸药物的药代动力学）等，再者或因肝肾功能异常降尿酸药物的使用存在禁忌等都可能导致RCG。
2012版ACR痛风管理指南-宋立军
(tophi) deposited chiefly in and around joints, which
sometimes lead to deformity and crippling
反应;
中国指南未提及。
4、痛风关节炎急性发作的抗炎 镇痛药选择：
ACR指南推荐NSAIDs、秋水仙碱和糖皮质激素，3种
药同等推荐，医师根据患者偏好、以前治疗反应、合
并症综合考虑;
中国指南建议糖皮质激素用于不能耐受NSAIDs和秋水
仙碱或肾功能不全者。
5、分层治疗的强调：
ACR指南强调分层治疗，痛风关节炎根据疼痛程度及
鼓励食用：低脂乳制品和蔬菜。
急性痛风性关节炎发作的基本治疗原则
急性痛风性关节炎发作必须采取药物治疗，且最好在
发病之初的24小时内开始。如果在ULT过程中出现急
性痛风性关节炎发作，不须暂停降尿酸药物。
要让患者知道诱发痛风性关节炎急性发作的原因，一
旦发作，患者应知晓基本处理原则；
要让患者认识到痛风是体内尿酸过度积累所致，只有
嘌呤的肉类、海鲜及果糖饮料的摄入，推荐低脂或脱
脂乳制品和蔬菜；
② 减少酒精摄入（特别是啤酒、白酒和烈酒），避免
酗酒，疾病活动的患者须戒酒，尤其是药物无法有效
控制病情进展及慢性痛风性关节炎患者。
研究人员将食物建议分为三类：避免食用、限制食用
和鼓励食用。
客观的说，这些建议都是来自某些孤立的临床研究，
受累关节数，决定选单药还是联合治疗，对联合治疗
方案也做了建议;
《美国风湿病学会欧洲抗风湿联盟痛风分类标准》解读
3、病理学标准
2、对于疑似痛风患者，医生可以根据该标准进行初步诊断。如果患者的临床 表现符合标准，则可以进一步进行影像学和病理学检查以明确诊断。如果患者的 临床表现不符合标准，则可能需要进一步检查以排除其他疾病的可能性。
Hale Waihona Puke 3、病理学标准3、在治疗方面，医生可以根据该标准对痛风患者进行分期治疗。对于急性发 作期患者，医生可以采取非甾体抗炎药、糖皮质激素等药物治疗以缓解疼痛和炎 症。对于慢性期患者，医生可以采取降尿酸治疗以降低血尿酸水平，预防痛风发 作。同时，医生还需要对患者进行生活方式的干预，如控制饮食、增加运动等， 以降低痛风复发的风险。
痛风概述
痛风概述
痛风是一种由于嘌呤代谢紊乱或尿酸排泄障碍导致的慢性代谢性疾病。根据 国家卫健委2019年的数据，我国痛风患病率呈逐年上升趋势，且发病年龄日趋年 轻化。痛风的主要病理生理机制是尿酸盐结晶沉积，导致急性痛风性关节炎和痛 风石形成。痛风患者常伴发高血压、糖尿病、肥胖、高血脂等代谢性疾病。
指南解读
要点分析
要点分析
1、分类：该指南将痛风分为急性发作期、间歇期和慢性期三个阶段，有助于 更好地理解患者的病情和制定相应的治疗方案。
要点分析
2、诊断：指南强调了病史采集、体格检查、实验室检查和影像学检查的重要 性，有助于提高诊断的准确性。
要点分析
3、治疗：该指南提出了针对不同阶段的治疗方案，包括抗炎、降尿酸和尿酸 盐溶解等治疗措施，具有很强的实操性。
在影像学方面，有以下两个标准： （1）关节超声：超声检查发现关节内有结晶沉积或痛风石；
2、影像学标准
（2）关节X线检查：X线平片显示关节周围有骨质破坏或囊性变。
3、病理学标准
3、病理学标准
2012美国ACR痛风指南(第一部分)
16North Mississippi Medical Center, Tupelo, MS 17Southern California Permanente Medical Group, Downey, CA 18University of Florida, Gainesville, FL 19Cleveland Clinic, Cleveland, OH 20University of Pennsylvania and VA Medical Center, Philadelphia, PA 21Harvard Vanguard Medical Associates/Atrius Health, Somerville, MA 22VA Medical Center. Birmingham, Alabama and University of Alabama, Birmingham, AL Keywords Allopurinol; Febuxostat; Probenecid; Pegloticase; Uricosuric; Xanthine Oxidase; Tophi INTRODUCTION Gout is a disorder that manifests as a spectrum of clinical and pathologic features built on a foundation of an excess body burden of uric acid, manifested in part by hyperuricemia,which is variably defined as serum urate greater than either 6.8 or 7.0 mg/dL (1;2). Tissue deposition of monosodium urate monohydrate crystals in supersaturated extracellular fluids of the joint, and certain other sites, mediates most of the clinical and pathologic features of gout. Typically, the disease first presents as arthritis that is acute and episodic, but can become recurrent in the majority of individuals. Gout also can manifest as chronic arthritis of one or more joints (1;2). Tophi, mainly in articular, periarticular, bursal, bone, auricular,and cutaneous tissues are a pathognomonic feature of gout, and are detectable by physical exam, and/or by imaging approaches and pathology examination (3;4;5). Renal manifestations of gout include urolithiasis, typically occurring with an acidic urine pH (1;2).Chronic interstitial nephropathy, mediated by monosodium urate monohydrate crystal deposition in the renal medulla, can occur in severe disease, but is currently considered to be an uncommon clinical manifestation of gout.Gout is one of the most common rheumatic diseases of adulthood, with self-reportedprevalence in the USA recently estimated at 3.9% of adults (~8.3 million people)(6).Prevalence of gout has risen in many countries (e.g., New Zealand), and especially in theUSA over the last few decades, mediated by factors such as increased prevalence of co-morbidities that promote hyperuricemia, including hypertension, obesity, metabolicsyndrome, type 2 diabetes, and chronic kidney disease (CKD)(7–10). Other factors in therising prevalence of gout include certain dietary trends and widespread prescription ofthiazide and loop diuretics for cardiovascular diseases (11). Many gout patients, includingthe growing subset of affected elderly, have complex co-morbidities and medication profilesthat complicate overall management (12). Long-term morbidity and impairment of health-related quality of life are now better appreciated in many gout patients, particularly thosewith multiple co-morbidities and/or chronic gouty arthritis (13;14). Despite advancedunderstanding of the molecular bases of hyperuricemia and gouty inflammation, and theextensive practice experience of many providers, substantial quality of care gaps exist ingout management (15). Moreover, significant shortfalls in patient education and adherencehave been identified in gout (16).On behalf of the American College of Rheumatology (ACR), we were charged withdeveloping systematic non-pharmacologic and pharmacologic recommendations foreffective treatments in gout with acceptable risk-benefit ratio. Our assignment was to focuson four specific domains in gout management. Two of these domains are addressed herein,(i) Urate-lowering therapy (ULT), and (ii) chronic gouty arthritis with tophaceous diseasedetected on physical examination (designated by the ACR with the terminology “chronictophaceous gouty arthropathy” (abbreviated CTGA), and specifically represented in theNIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author Manuscriptfundamental case scenarios 7–9 described herein). Domains iii-iv (analgesic and anti-inflammatory management of acute gouty arthritis, and pharmacologic anti-inflammatory prophylaxis of attacks of gouty arthritis, respectively) are addressed in a separate manuscript (Part II of the guidelines)(17).There are multiple lines of epidemiologic and experimental evidence that hyperuricemia, via effects of excess soluble urate, may play a role in some human renal, cardiovascular, and metabolic co-morbidities also frequently associated with gout (7–10). We did not address pharmacologic management of asymptomatic hyperuricemia, due to a paucity of prospective, randomized, controlled human research trials in that area (18).We were charged by the ACR with developing gout recommendations based on evidence as available, at an international level, for rheumatologists and other health care providers,including other subspecialists, primary care practitioners, nurse practitioners, physician assistants, and allied health professionals. The ACR requested that we apply the established Research and Development/University of California at Los Angeles (RAND/UCLA)Appropriateness Method (19) to generate recommendations, and engaged a diverse,international panel of experts. Creating novel classification of gout as a disease, new gout diagnostic criteria, or definition of treatment outcomes were beyond the scope of this work.Instead, we generated multifaceted case scenarios to elucidate decision-making based primarily on clinical and laboratory test-based data that can be obtained on a gout patient in an office practice setting.Guidelines for gout management have been generated in the last decade, at the national or multinational society level, by the European League Against Rheumatism (EULAR)(20;21),the Dutch College of General Practitioners (22), the Japanese Society of Gout and Nucleic Acid Metabolism (23), and the British Society for Rheumatology (BSR)(24). Moreover, the National Institute for Health and Clinical Excellence (NICE) single technology appraisal (STA) process has been applied to ULT in gout using febuxostat (25). New guidelines wererequested by the ACR, as the understanding of gout risk factors has been greatly augmented by recent clinical research (12). Moreover, ULT options recently increased via clinicaldevelopment, and drug regulatory agency approval of new pharmacologic agents (febuxostat and the biologic drug pegloticase)(26;27). New imaging approaches for gout that can detect radiographic changes of early disease not visualized by plain radiography (e.g., highresolution ultrasound, dual energy computed tomography (DECT)(28;29), are beinginvestigated for impact on gout diagnosis, and assessment of disease burden and severity,and choices and effectiveness of management. Developments such as these are considered in the work of this committee, which was built on several key assumptions (Table 1).The ACR gout guidelines are designed to emphasize safety, and quality of therapy, and to reflect best practice, as evaluated by a diverse group of experts that examine the level ofevidence available at the time. Importantly, societal cost of health care, and cost and cost-effectiveness differences between therapies are excluded from analysis by the RAND/UCLA Appropriateness Methodology (19) (Table 1). Individual results of this work are designated as “recommendations” rather than guidelines, in order to reflect the non-prescriptive nature of decision-making evaluated by experts, and based on available evidence at the time. The recommendations cannot substitute for individualized, direct assessment of the patient,coupled with clinical decision making by a competent health care practitioner. Treatment recommendations also assume appropriate attention to potential drug interactions (eg, with anticoagulants, azathioprine, amoxicillin), and effects of co-morbidities such as diabetes,and renal, cardiac, gastrointestinal, and hepatic disease (Table 1). The motivation, financial circumstances, and preferences of the gout patient play a very important role. Moreover, the NIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author Manuscriptrecommendations for gout management presented here are not intended to limit or denythird party payer coverage of health care costs for groups, or individual patients, with gout.METHODSProject design and development of recommendations and grading of evidence The overall design of the project is schematized in Supplemental Figure 1. The RAND/UCLA consensus methodology, developed in the 1980s, incorporates both Delphi and nominal group methods (19;30), and was successfully used to develop other guidelines commissioned by the ACR. The purpose of this methodology is to reach a consensus among experts, with an understanding that published literature may not be adequate to provide sufficient evidence for day-to-day clinical decision-making. The RAND/UCLA method requires 2 groups of experts—a core expert panel (CEP) that provides input into case scenario development and preparation of a scientific evidence report, and a task force panel (TFP) that votes on these case scenarios. Our CEP consisted of leaders for each domain (Supplemental Figure 2). Pharmacologic approaches, and diet, lifestyle and non-pharmacologic measures (e.g., weight loss, exercise) were addressed within each domain.The CEP leaders communicated with an international panel of gout experts, and the PIs, to develop initial case scenarios that reflect broad differences in severity of the disease and its clinical manifestations. In addition, there were weekly interactive teleconferences between domain leaders and PIs to refine case scenarios. Though previous systematic review for gout has been performed by EULAR, as a prime example, we performed our own systematic review of pertinent literature. The resultant scientific evidence report given to the TFP in conjunction with clinical scenarios representing a broad scope of disease, with multiple questions of interest, and alternative options, for each case scenario.By ACR mandate, the TFP had a majority of members without perceived potential conflict of interest (COI), and had diverse experience and expertise, as described in detail inSupplemental Figure 2. The TFP included 7 rheumatologists (one of whom is a Chair ofInternal Medicine, and one an Internal Medicine Residency Training Program Director), 2primary care physicians, a nephrologist, and a patient representative. There were 2 rounds of ratings, the first anonymously with the members of the TFP instructed to rank each of the potential elements of the guidelines on a risk-benefit basis ranging from 1 to 9 on a Likert scale using Delphi process, followed by a face-to-face group discussion and then re-voting of the same scenarios. A vote of 1–3 on the Likert Scale was rated as Inappropriate = risks clearly outweigh the benefits. A vote of 4–6 on the Likert Scale was considered Uncertain =risk-benefit ratio is uncertain. A vote of 7–9 on the Likert Scale was rated as Appropriate =benefits clearly outweigh the risks. Samples of votes taken and results are provided inSupplemental Figure 3. Votes on case scenarios were translated into recommendations if the median voting score was graded 7–9 (“appropriate”) and if there was no significantdisagreement, defined as no more than 1/3 of the votes graded (“inappropriate”) for thescenario. The final rating was done anonymously in a 2-day face-to-face meeting, facilitated by an experienced moderator (Neil Wenger). During the face-to-face TFP meeting, some case scenarios were clarified for content or verbiage, and re-voted on by the TFP.The level of evidence supporting each recommendation was ranked based on previousmethods used by the American College of Cardiology (31) and applied to recent ACRrecommendations (32;33). Level A grading was assigned to recommendations supported by multiple (i.e., more than one) randomized clinical trials or meta-analyses. Level B grading was assigned to the recommendations derived from a single randomized trial, ornonrandomized studies. Level C grading was assigned to consensus opinion of experts, case studies, or standard-of-care.NIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author ManuscriptSystematic reviewPubMed and Cochrane Central Register of Controlled Trials (CENTRAL) from the 1950s to the present were searched to find articles on gout with help of an experienced librarian(Rikke Ogawa). We used a search strategy based on the Cochrane Highly Sensitive Search Strategy for identifying randomized trials. The search was expanded to include articlesdiscussing research designs such as cohort, case control and cross sectional studies. Limits included English Language and the exclusion of “animal only” studies. The exact terms,process and results of the search are summarized in Supplemental Figure 4.Clinical Case DescriptionsThe TFP evaluated scenarios with a broad spectrum of clinical gout, similar to what aclinician might see in a busy practice, and divided into mild, moderate, and severe disease activity in each of three distinct “treatment groups” (Figure 1A–B). In generating these nine fundamental clinical case scenarios, mild disease activity levels in each “treatment group”were meant to represent patients at the lowest disease activity level for which mostclinicians would consider initiating or altering a specific medication regimen. Conversely,severe disease activity level was intended to represent patients with disease activity equal or greater to that of the “average” subject studied in a clinical trial. The case scenarios were not intended to serve as classification criteria. To allow the TFP to focus on managementdecisions, each case scenario had the assumption not only that the diagnosis of gout was correct, and that there was some clinical evidence of gout disease activity. This included intermittent symptoms of variable frequency, specifically presented to the TFP as episodes of acute gouty arthritis of at least moderate to severe pain intensity (17). Clinical evidence of gout disease activity, presented to the TFP, also included one or more tophi detected byphysical exam, or alternatively, chronic symptomatic arthritis (ie, “chronic arthropathy” or “synovitis”) due to gout, with or without confirmed joint damage (e.g., deformity, erosion due to gout on imaging study). Hyperuricemia was defined here as serum urate >6.8 mg/dL(2). We determined all aspects of case scenario definitions by a structured iterative process,using regular electronic mail, and teleconferences at least once per month. Multiplerevisions to the proposed parameters were carried out, until accepted by the CEP domain leaders.Definitions of pharmacologic therapeutic agentsMedication classes evaluated in the case scenarios were defined as follows: Xanthineoxidase inhibitor (XOI) refers to allopurinol or febuxostat; uricosuric agents were defined to include agents available in the USA (probenecid, and off-label use (as uricosuric therapy) of fenofibrate and losartan), but did not include sulfinpyrazone or benzbromarone. Other agents and modalities were self-explanatory. Evaluation by the TFP of effectiveness of a giventherapeutic option assumed that patients in case scenarios received the maximum tolerated typical dose for a period of time sufficient to accurately assess therapeutic response, unless otherwise indicated.Managing perceived potential COIPerceived potential COI was managed in a prospective and structured manner. Specifically,all participants intellectually involved in the project, whether authors or not, were required to fully, and prospectively disclose relationships with pharmaceutical companies with amaterial interest in gout (Supplemental Material Discussion). Disclosures were updatedevery 6 months, and for the PIs, CEP and TFP, updated just prior to the face-to-facemeeting. A summary listing of all perceived potential COI was disseminated to allparticipants in the project, and is available in the supplemental materials. Based on thepolicies of the ACR, which are aligned with those of many medical societies, no more than NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript49% of project participants could have COI at any given time. It was required that theproject PI (John FitzGerald) remain without perceived potential COI prior to and during the process.RESULTS Primary principles of management for all gout case scenarios The TFP generated recommendations for a systematic non-pharmacologic and pharmacologic management approach intended to be applicable to all patients with gout,which is summarized in Figure 3. This was based on the assumption that the diagnosis of gout was correct before initiation of management. The approach highlighted patient education on the disease and treatments and their objectives, and initiation of diet and lifestyle recommendations. The TFP also recommended elimination of prescription medication that were non-essential for the optimal management of co-morbidities (eg,hypertension, CHF, hyperlipidemia, or major organ transplant) in an individual patient,where such medication elevated serum urate levels; with prime examples being thiazide and loop diuretics, niacin, and calcineurin inhibitors (Evidence C). Though low dose acetylsalicylic acid (aspirin ≤ 325 mg daily) elevates serum urate, the TFP did not recommend discontinuation of this modality as cardiovascular disease prophylaxis in gout patients. In discussion, without a specific vote, the TFP viewed the relative risks specifically attributable to the modest effects of low dose aspirin on serum urate as negligible in gout management.The TFP recommended that clinicians consider causes of hyperuricemia for all gout patients,and recommended a specific co-morbidity checklist (Evidence C)(Table 2). In doing so, the TFP specially recommended consideration, and if indicated, medical evaluation of certain agents and disorders that cause uric acid underexcretion or overproduction, and thereby could merit laboratory investigations such as urinalysis, renal ultrasound, a completehemogram, or urine uric acid quantification as indicated. In this context, the TFPspecifically recommended screening for uric acid overproduction (by urine uric acidevaluation for uric acid overproduction), in patient subsets with gout clinical disease onset before age 25 (Evidence C), or a history of urolithiasis (Evidence C).The TFP provided guidance for referral to a specialist, with caution to avoid appearing self-serving. Though limited by the absence of outcomes data on potential benefits of referral,the TFP recommended that gout case scenarios including any of the following should be amongst those where referral to a specialist is considered (Evidence C for all): (i) Unclear etiology of hyperuricemia; (ii) Refractory signs or symptoms of gout; (iii) Difficulty inreaching the target serum urate level, particularly with renal impairment and a trial of XOI treatment; (iv) Multiple and/or serious adverse events from pharmacologic ULT.Clinical evaluation of gout disease activity and burdenThe TFP recommended clinical evaluation of gout disease symptom severity and burden in individual patients by history and thorough physical exam for symptoms of arthritis, and signs such as tophi and acute and chronic synovitis (Evidence C). To be actionable byclinicians, the authors, without a specific TFP vote, suggest that clinicians can work with patients to record and estimate the number per year, and severity (17) of acute attacks of gouty arthritis per year.Core recommendations for non-pharmacologic ULT measures in goutThe TFP recommended certain diet and lifestyle measures for the vast majority of patients with gout (Evidence B-C for individual measures) (Figure 4). Many of the diet and lifestyle NIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author Manuscriptmeasures were recommended for decreasing the risk and frequency of acute gout attacks(12) and lowering serum urate, but the primary emphasis of the TFP recommendations in Figure 4 was on diet and lifestyle choices for promotion and maintenance of ideal health,and prevention and optimal management of life-threatening comorbidities in gout patients,including coronary artery disease (34,35), and obesity, metabolic syndrome, diabetes,hyperlipidemia, and hypertension.Dietary recommendations were grouped into 3 simple qualitative categories, termed “limit”,“avoid”, or “encourage” (Figure 4). This approach, with rare exceptions (36,37), reflected a general lack of specific evidence from prospective, blinded, randomized clinical intervention trials that linked consumed quantities of individual dietary components to changes in either serum urate levels or gout outcomes. Notably, the replication of hazardous lifestyle riskfactors in a conventional clinical research trial would potentially pose both design andethical difficulties. As such, the TFP deliberated on evidence regarding the impact ofexposures to alcohol or purine-rich foods in a short time frame. The evidence sources were epidemiologic studies of hyperuricemia and incident gout, including long-term prospective analyses and internet-based case-crossover studies. The TFP recommended that goutpatients limit their consumption of purine-rich meat and seafood (Evidence B) as well as high fructose corn syrup sweetened soft drinks and energy drinks (Evidence C), andencouraged the consumption of low-fat or non-fat dairy products (Evidence B) (38)(Figure4). The TFP also recommended reduced consumption of alcohol (particularly beer, but also wine and spirits), and avoidance of alcohol overuse in all gout patients (Evidence B) (Figure4). The TFP further recommended abstinence from alcohol consumption for gout patients during periods of active arthritis, especially with inadequate medical control of the disorder and in CTGA (Evidence C)(39). Significantly, in discussion by the TFP, without a specific vote, the TFP recognized that diet and lifestyle measures alone provide therapeuticallyinsufficient serum urate-lowering effects and/or gout attack prophylaxis for a large fraction of individuals with gout (12). For example, some clinical trials on diet and fitness havereported only ~10–18% decrease in serum urate (38). In further discussion by the TFP, again without a specific vote, the TFP viewed this degree of serum urate-lowering as beneficial for all case scenarios, but insufficient to achieve an effective serum urate target in those with sustained hyperuricemia substantially above 7 mg/dL.Core recommendations for pharmacologic ULT, including the serum urate targetHere, and with all other recommendations for drug therapy in Parts I and II of the 2012 ACR Guidelines for gout, the recommendations assumed a lack of contra-indications, intolerance,serious adverse events, or drug-drug interactions for given agents. The TFP recommended gout with CKD stage 2–5, or end stage renal disease (ESRD), as an appropriate indication,by itself, for pharmacologic ULT (Evidence C) in patients with prior gout attacks andcurrent hyperuricemia. In pharmacologic ULT, certain treatment choices (e.g., probenecid)and drug dosing decisions (e.g., allopurinol) are impacted by the creatinine clearance. The TFP, without a direct vote, discussed and recognized the clinical value of accuratemeasurement of creatinine clearance, not simply the serum creatinine, in ascertaining the degree of renal impairment. However, the scope of the project did allow for detailed,prescriptive recommendations regarding specific ULT drug doses, or usage of individual agents in the presence of a given degree of either renal impairment, or other co-morbidities such as hepatic impairment.TFP recommendations for pharmacologic ULT, presented graphically in Figure 3, included recommendation of xanthine oxidase inhibitor (XOI) therapy with either allopurinol orfebuxostat as the first line pharmacologic approach (Evidence A). The panel did notpreferentially recommend either XOI over the other XOI drug. In doing so, the TFP weighed the lack of published safety data for febuxostat in the setting of stage 4 or worse CKD.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptProbenecid was recommended as an alternative first line pharmacologic ULT option, in the setting of contra-indication or intolerance to at least one XOI agent (Evidence B). However,the TFP did not recommend probenecid as a first line ULT monotherapy in those with acreatinine clearance below 50 ml/min.The TFP recommended that pharmacologic ULT could be started during an acute goutattack, providing that effective anti-inflammatory management has been instituted (EvidenceC). The TFP recommended regular monitoring of serum urate (every 2–5 weeks) duringULT titration, including continuing measurements once the serum urate target is achieved (every 6 months) (Evidence C). The TFP weighed this measure as particularly useful tomonitor adherence, given that poor adherence to ULT is a common problem in gout patients(16).The TFP recommended that the goal of ULT is to achieve a serum urate target, at aminimum, of < 6 mg/dL in all gout case scenarios (Evidence A). Moreover, the TFPrecommended that the target serum urate should be lowered sufficiently to durably improve signs and symptoms of gout, including palpable and visible tophi detected by physicalexamination, and that this may involve therapeutic serum urate-lowering to below 5 mg/dL (Evidence B).Recommendations specific to allopurinol dosing and pharmacogenetics TFP recommendations for use of allopurinol in gout are summarized in Table 3A.Importantly, the TFP recommended that the starting dose of allopurinol be no greater than 100 mg per day (Evidence B)(40), consistent with prior FDA and EULAR guidelines (21).The rationale of the TFP was partly that a low allopurinol starting dose could reduce early gout flares after ULT initiation, (26), and partly as a component of risk management with respect to the potential for severe hypersensitivity reaction to allopurinol (40), discussed in further detail below. The TFP recommended gradual upward titration of the allopurinolmaintenance dose every 2–5 weeks to an appropriate maximum dose for gout, in order to treat to the serum urate target appropriate for the individual patient (Evidence C).The TFP weighed robust evidence that allopurinol monotherapy at doses of 300 mg daily or less failed to achieve the serum urate target of <6 mg/dL (26,41), or < 5 mg/dL (42,43), in more than half of subjects with gout. The TFP reviewed small studies in which theallopurinol dose was titrated above 300 mg daily in gout with overall success in achieving the serum urate target (43,44). Importantly, in doing so, the TFP also recommended that the maintenance dose of allopurinol can be raised above 300 mg per day, even in those withrenal impairment, provided there is adequate patient education and regular monitoring for drug hypersensitivity and other adverse events, such as pruritis, rash, and elevated hepatic transaminases, as well as attention to potential development of eosinophilia (Evidence B).The TFP next considered the issue of measures to reduce the incidence of severe allopurinol hypersensitivity reactions, here termed allopurinol hypersensitivity syndrome (AHS). TFP discussion recognized the potential for hospitalization and severe morbidity, and thereported mortality rate of 20–25% in AHS (45,46). The estimated incidence of AHS is~1:1000 in the USA and its spectrum includes not only Stevens-Johnson Syndrome andToxic Epidermal Necrolysis, but also systemic disease with a clinical constellation offeatures such as eosinophilia, vasculitis, rash, and major end-organ disease (47). Concurrent thiazide use and renal impairment have been implicated as risk factors for AHS (48–50). A widely employed risk management strategy has been a non-evidence-based algorithm for allopurinol maintenance dosing, calibrated to renal impairment (51)(Evidence C);importantly, the TFP did not recommend this strategy,NIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author Manuscript。
2012 ACR RA诊断治疗指南
A.加MTX、HCQ或LEF
再评价
B.加或转其他DMARD
再评价
有严重不良反应
再评价或有非FDA规定的严 重不良反应
F.转换另外一种TNF拮抗剂或非TNF拮抗剂 再评价 G.转换成另一种TNF拮抗剂或者非TNF拮抗剂
长病程RA: ≥6个月或符合1987 ACR分类标准
Singh JA, Arthritis Care Res (Hoboken). 2012;64(5):625-39
高
中
无
预后不良因素
有
无
预后不良因素
有
DMARD 单药治疗 早期RA (病程<6个月)
DMARD联合 (二或三联)治疗
DMARD单药或 HCQ+MTX
TNF拮抗剂+/-MTX 或DMARD联合 (二联或三联) 治疗
2012 ACR RA指南推荐：TNF拮抗剂是 中重度长病程RA，DMARDs治疗无效后最佳方案
2012 ACR RA指南定义的预后不良因素包括： 基线期存在骨侵蚀、类风湿因子或抗CCP抗2 ACR RA指南推荐：TNF拮抗剂联合MTX是 高疾病活动度伴预后不良因素早期RA的一线治疗方案
低
以 达 到 低 疾 病 活 动 度 或 者 缓 解 为 目 标
疾病活动度
以 达 到 低 疾 病 活 动 度 或 者 缓 解 为 目 标
E.换成非TNF生物制剂 C.加或转换为TNF拮抗剂 D.加或转为 阿巴西普或利妥昔 再评价或有任何不良 反应 DMARD单药 再评价 MTX单药或包括MTX在内的DMARD联合治疗 再评价 低疾病活动度无预后不良因素 低疾病活动度有预后不良因素或至少中活动度
11 ～ 26 >26
痛风指南：发达国家是这样治疗痛风的
痛风指南：发达国家是这样治疗痛风的前沿：痛风是一种最常见的炎症性关节病，在西方国家男性的患病率约为1%～2%。
随着我国人民生活水平的不断提高，痛风的患病率也呈逐年上升趋势，目前已经接近西方发达国家水平。
痛风是由于血尿酸水平持续升高，导致单钠尿酸盐在关节和其他组织中沉积所致。
高尿酸血症和痛风与糖尿病、高血压、心血管疾病、慢性肾脏病等密切相关，是上述疾病发生发展的独立危险因素，也直接导致了患者长期生活质量的下降。
2002～2008年荷兰全科医师学会、欧洲风湿病学会、英国风湿病学会以及日本痛风和核酸代谢学会均陆续颁布了痛风治疗指南，为合理规范化诊治痛风提供了重要依据。
治疗药物和新型影像学技术（高频超声和双能CT）的应用进一步推动了痛风诊治的发展。
2012年美国风湿病学会在循证医学证据基础上，结合专家根据患者具体临床情况给出的意见，针对痛风治疗提出了新的指南，包括非药物性干预和药物治疗。
2013年多个国家又联合提出了痛风诊断和治疗推荐。
为了更好地指导我国临床医师在实践中结合患者具体情况制订合理的治疗方案。
1痛风的治疗目标：普遍目标：痛风的治疗目标已经非常明确，最新的几项推荐或指南一致强调血尿酸水平降至360μmol/L（6mg/dl）以下是治疗的最低目标；痛风石患者目标：对于已有痛风石的痛风患者，为了更好地长期改善患者的临床症状和体征，应将血尿酸水平降至300μmol/L（5mg/dl）以下。
因此在治疗过程中需要严密监测患者血尿酸水平，另外也需要关注关节炎发作的频率和痛风石的大小。
最终目标：对于痛风患者，关节炎不再发作、痛风石逐渐被吸收也是治疗的重要目标。
2痛风的诊断：在关节积液或痛风石中发现单钠尿酸盐晶体仍然是诊断痛风的最有利依据。
临床发现典型痛风石或对秋水仙碱治疗反应好，支持痛风诊断，除此以外的多数情况下，临床、实验室以及传统X线检查对于诊断的帮助不大。
对于11项研究的荟萃分析显示：新型影像学技术（超声、双能CT）对于痛风诊断有帮助。
安康信的止疼效果
产品成分与制作工艺
安康信的主要成分是高纯度天然 植物提取物，这些成分经过精心 挑选和提取，以确保最佳的止疼
效果。
制作工艺方面，安康信采用了先 进的生产技术和质量控制流程，
确保产品的品质和稳定性。
安康信的生产过程严格遵循相关 法规和标准，确保产品的安全性
和有效性。
02
安康信的止疼原理
药物作用机理
抑制前列腺素合成
抑制中枢神经敏感化
安康信通过抑制前列腺素的合成，降 低炎症反应，从而缓解疼痛。
安康信能够抑制中枢神经敏感化，降 低疼痛的敏感性，从而缓解慢性疼痛。
抗炎作用
安康信具有抗炎作用，能够减轻炎症 引起的疼痛和肿胀。
止疼效果的科学依据
01
02
03
临床研究
多项临床研究证实了安康 信在止疼方面的有效性， 支持其用于缓解疼痛。
长期止疼效果
长期使用
对于需要长期管理疼痛的患者， 安康信可以提供持续的疼痛缓解。
预防疼痛复发
长期使用安康信有助于预防疼痛 的复发，降低疼痛再次出现的风
险。
减少药物依赖
长期使用安康信可以减少患者对 其他止痛药的依赖，提高疼痛管
理的自主性。
适用人群与使用方法
适用人群
适用于成年人及老年人的轻度至中度疼痛治疗， 需在医生指导下使用。
总结
安康信与其他止疼药在成分上相似，均具有抗炎、镇痛作用。
止疼效果比较
安康信
01
依托考昔具有强效的抗炎镇痛作用，对于轻至中度疼痛的缓解
效果较好。
其他止疼药
02
如布洛芬、对乙酰氨基酚等，对于轻至中度疼痛的缓解效果也
较好。
总结
03
在止疼效果方面，安康信与其他常见止疼药相当，均能有效缓
安康信依托考昔片说明书
安康信（依托考昔片）说明书【安康信药品名称】通用名：依托考昔片商品名：安康信（ARCOXIA）英文名：EloricoxibTablets 汉语拼音：YituokaoxiPian安康信成份】主要成份为依托考昔。
化学名称：5-氟-6‘- 甲基-3-[4- （甲磺酰基）苯基]-2 ，3'-联吡啶。
【安康信性状】安康信为薄膜衣片，除去包衣后显白色或类白色。
60mg规格：绿色片；90mg 规格：白色片；120mg规格：淡绿色片。
【安康信适应症】安康信适用于治疗急性痛风性关节炎。
【安康信规格】120mg【安康信用法用量】安康信用于口服，可与食物同服或单独服用。
急性痛风性关节炎-- 推荐剂量为120 毫克，每日1 次。
安康信120毫克只适用于症状急性发作期，长使用8 天。
使用剂量大于推荐剂量时，尚未证实有更好的疗效或目前尚未研究。
因此，上述剂量是推荐剂量。
因为选择性环氧化酶-2 抑制剂的心血管危险性会随剂量升高和用药时间延长而增加，所以应尽可能减短用药时间和使用每日有效剂量。
应定期评估患者症状的缓解情况和患者对治疗的反应。
（见注意事项）老年人、性别、种族-- 老年人、不同性别和种族的人群均不需调整剂量。
肝功能不全-- 轻度肝功能不全患者（Child-Pugh 评分5-6 ），安康信使用剂量不应超过60 毫克每日1次。
中度肝功能不全患者（Child-Pugh 评分7-9 ），应当减量，不应超过隔日60 毫克。
对重度肝功能不全患者（Child-Pugh 评分＞9），目前尚无临床或药代动力学资料。
（见注意事项）肾功能不全-- 患有晚期肾脏疾病（肌酐清除率＜30mL/min ）的患者不推荐使用安康信。
对于轻度肾功能不全（肌酐清除率≥30mL/min ）不需要调整剂量。
（见注意事项）【安康信不良反应】据国外文献报道在临床试验中，对约4800例个体进行了安全性评价，包括约3400 例骨关节炎、风湿性关节炎或慢性腰背痛的患者（约600例骨关节炎或风湿性关节炎患者治疗达 1 年或更长时间）。