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Treat-to-target recommendations in giant cell arteritis and polymyalgia rheumatica
巨细胞动脉炎和风湿性多肌痛的靶向治疗建议
  1. Christian Dejaco1,2,
  2. Andreas Kerschbaumer3,
  3. Daniel Aletaha4,
  4. Milena Bond2,
  5. Elvis Hysa5,
  6. Dario Camellino6,
  7. Lisa Ehlers7,
  8. Andy Abril8,
  9. Simone Appenzeller9,
  10. Maria C Cid10,
  11. Bhaskar Dasgupta11,
  12. Christina Duftner12,
  13. Peter C Grayson13,
  14. Bernhard Hellmich14,
  15. Alojzija Hočevar15,16,
  16. Tanaz A Kermani17,
  17. Eric L Matteson18,
  18. Susan P Mollan19,20,
  19. Lorna Neill21,
  20. Cristina Ponte22,23,
  21. Carlo Salvarani24,25,
  22. Sebastian Eduardo Sattui26,
  23. Wolfgang A Schmidt27,
  24. Philip Seo28,
  25. Josef S Smolen29,
  26. Jens Thiel1,30,
  27. Carlos Enrique Toro-Gutiérrez31,
  28. Madeline Whitlock32,
  29. Frank Buttgereit33

    30. http://orcid.org/0000-0002-0173-0668Christian Dejaco 1, 2, http://orcid.org/0000-0002-6685-8873Andreas Kerschbaumer 3, http://orcid.org/0000-0003- 2108-0030丹尼尔·阿莱塔哈 4，http://orcid.org/0000-0002-5400-2955米莱娜·邦德 2，埃尔维斯·海萨 5，http://orcid.org/0000-0001-6384-6458达里奥·卡梅利诺 6，http:// orcid.org/0000-0001-8737-001XLisa Ehlers 7，安迪·阿布里尔 8，西蒙娜·阿彭泽勒 9，http://orcid.org/0000-0002-4730-0938Maria C Cid 10，http://orcid.org/0000 -0002-5523-6534Bhaskar Dasgupta 11，http://orcid.org/0000-0003-3137-8834Christina Duftner 12，http://orcid.org/0000-0002-8269-9438Peter C Grayson 13，http:// orcid.org/0000-0002-8014-1801Bernhard Hellmich 14，http://orcid.org/0000-0002-7361-6549Alojzija Hočevar 15, 16，http://orcid.org/0000-0002-7335-7321Tanaz A Kermani 17，http://orcid.org/0000-0002-9866-0124Eric L Matteson 18，Susan P Mollan 19, 20，Lorna Neill 21，http://orcid.org/0000-0002-3989-1192Cristina Ponte 22 , 23, http://orcid.org/0000-0003-3708-3148卡洛·萨尔瓦拉尼 24, 25, http://orcid.org/0000-0002-3945-6828塞巴斯蒂安·爱德华多·萨图伊 26, http://orcid.org/ 0000-0001-7831-8738Wolfgang A Schmidt 27, Philip Seo 28, http://orcid.org/0000-0002-4302-8877Josef S Smolen 29, Jens Thiel 1, 30, http://orcid.org/0000- 0002-6084-7049卡洛斯·恩里克·托罗-古铁雷斯 31，马德琳·惠特洛克 32，http://orcid.org/0000-0003-2534-550XFrank Buttgereit 33
  1. Correspondence to Dr Christian Dejaco, Division of Rheumatology and Clinical Immunology, Department of Internal Medicine, Medical University of Graz, Graz, 8036, Austria; christian.dejaco@gmx.net
    通讯作者：Christian Dejaco 博士，格拉茨医科大学内科风湿病学和临床免疫学科，格拉茨，8036，奥地利； christian.dejaco@gmx.net

Abstract 抽象的

Objectives To develop treat-to-target (T2T) recommendations in giant cell arteritis (GCA) and polymyalgia rheumatica (PMR).
目的 制定巨细胞动脉炎 (GCA) 和风湿性多肌痛 (PMR) 的靶向治疗 (T2T) 建议。

Methods A systematic literature review was conducted to retrieve data on treatment targets and outcomes in GCA/PMR as well as to identify the evidence for the effectiveness of a T2T-based management approach in these diseases. Based on evidence and expert opinion, the task force (29 participants from 10 countries consisting of physicians, a healthcare professional and a patient) developed recommendations, with consensus obtained through voting. The final level of agreement was provided anonymously.
方法进行系统文献综述，以检索 GCA/PMR 治疗目标和结果的数据，并确定基于 T2T 的管理方法在这些疾病中的有效性的证据。根据证据和专家意见，工作组（来自 10 个国家的 29 名参与者，包括医生、医疗保健专业人员和患者）制定了建议，并通过投票获得了共识。最终协议是匿名提供的。

Results Five overarching principles and six-specific recommendations were formulated. Management of GCA and PMR should be based on shared decisions between patient and physician recognising the need for urgent treatment of GCA to avoid ischaemic complications, and it should aim at maximising health-related quality of life in both diseases. The treatment targets are achievement and maintenance of remission, as well as prevention of tissue ischaemia and vascular damage. Comorbidities need to be considered when assessing disease activity and selecting treatment.
结果 制定了五项总体原则和六项具体建议。 GCA 和 PMR 的管理应基于患者和医生之间的共同决策，认识到需要紧急治疗 GCA 以避免缺血性并发症，并且应旨在最大限度地提高这两种疾病的健康相关生活质量。治疗目标是实现和维持缓解，以及预防组织缺血和血管损伤。评估疾病活动性和选择治疗方法时需要考虑合并症。

Conclusion These are the first T2T recommendations for GCA and PMR. Treatment targets, as well as strategies to assess, achieve and maintain these targets have been defined. The research agenda highlights the gaps in evidence and the need for future research.
结论 这些是针对 GCA 和 PMR 的首个 T2T 建议。治疗目标以及评估、实现和维持这些目标的策略已经确定。研究议程强调了证据的差距和未来研究的必要性。

  • Giant Cell Arteritis
  • Polymyalgia Rheumatica
  • Biological Therapy
  • Outcome and Process Assessment, Health Care
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https://doi.org/10.1136/ard-2022-223429

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WHAT IS ALREADY KNOWN ON THIS TOPIC
关于该主题的已知信息

  • There is large heterogeneity in clinical practice related to treatment strategies in giant cell arteritis (GCA) and polymyalgia rheumatica (PMR).
    巨细胞动脉炎（GCA）和风湿性多肌痛（PMR）治疗策略的临床实践存在很大的异质性。

  • The concept of treat-to-target (T2T) is widely adopted in rheumatology, but has yet not been defined for these diseases.
    靶向治疗（T2T）的概念在风湿病学中被广泛采用，但尚未针对这些疾病进行定义。

WHAT THIS STUDY ADDS 这项研究增加了什么

  • Here, we present consensus-based recommendations on T2T in GCA and PMR developed by an international, multidisciplinary task force.
    在这里，我们提出了由国际多学科工作组制定的关于 GCA 和 PMR 中 T2T 的基于共识的建议。

  • Treatment targets, as well as strategies to assess, achieve and maintain these targets, have been provided.
    已经提供了治疗目标以及评估、实现和维持这些目标的策略。

HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY
这项研究可能如何影响研究、实践或政策

  • These recommendations advise clinicians how to effectively implement a T2T approach for GCA and PMR in clinical practice.
    这些建议建议临床医生如何在临床实践中有效实施 GCA 和 PMR 的 T2T 方法。

  • Gaps in current knowledge have been identified and a research agenda frames the needs to be addressed by future studies in the field.
    已经确定了当前知识的差距，并制定了研究议程，确定了该领域未来研究需要解决的需求。

Introduction 介绍

Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are overlapping inflammatory rheumatic conditions of older people.1 2 For decades, GCA has been considered a predominantly cranial disease. More recently, advanced vascular imaging has demonstrated that large vessels (LV) are frequently involved, leading to the understanding that GCA represents a generalised vasculitic syndrome that includes cranial and extracranial medium/LV vasculitis (LV-GCA) and overlaps with PMR.3
巨细胞动脉炎（GCA）和风湿性多肌痛（PMR）是老年人的重叠炎症风湿病。 1 2 几十年来，GCA 一直被认为是一种主要的颅脑疾病。最近，先进的血管成像显示大血管 (LV) 经常受累，从而认识到 GCA 代表一种全身性血管炎综合征，包括颅内和颅外中/LV 血管炎 (LV-GCA)，并与 PMR 重叠。 3

Glucocorticoids (GC) are the standard treatment for GCA and PMR. Unfortunately, GC-related toxicity occurs in up to 85% of patients.1 2 In addition, many patients have pre-existing comorbidities that may worsen with GC therapy. Moreover, the prevalence of symptomatic disease relapse is high: in cohort studies, 34–62% of people with GCA and/or PMR were reported to have at least one relapse.4 In a clinical trial in GCA comparing tocilizumab (TCZ) with placebo along with a standardised GC tapering, sustained remission was achieved in only one-fifth of those who were treated with GC alone.5 Tapering of GCs, however, was much faster in that study as compared with clinical practice. (Hysa et al, manuscript in preparation)
糖皮质激素 (GC) 是 GCA 和 PMR 的标准治疗方法。不幸的是，高达 85% 的患者会出现 GC 相关毒性。 1 2 此外，许多患者已有合并症，GC 治疗后这些合并症可能会恶化。此外，有症状疾病复发的患病率很高：在队列研究中，据报道，34-62% 的 GCA 和/或 PMR 患者至少有一次复发。 4 在一项 GCA 临床试验中，将托珠单抗 (TCZ) 与安慰剂以及标准化 GC 逐渐减量进行比较，结果显示，仅五分之一的仅接受 GC 治疗的患者获得了持续缓解。 5 然而，该研究中 GC 的逐渐减少速度比临床实践要快得多。 （Hysa 等人，手稿正在准备中）

Methotrexate, in combination with GC, can be considered in the treatment of patients with GCA and PMR, even though data from clinical trials revealed conflicting results.6–8 TCZ has been approved for treatment in GCA following the phase III study mentioned above, which demonstrated higher remission rates and better GC sparing than placebo.5 Notably, neither drug has so far been associated with a reduction in GC-related adverse outcomes. For PMR, TCZ was also highly effective in recent phase II/III trials but has not yet been approved for this disease indication.9 10 Another phase III trial of sarilumab in PMR was terminated early because of the COVID-19 pandemic. Preliminary results indicated a higher efficacy of sarilumab over placebo in terms of achieving sustained remission.11 Other drugs are currently being tested in randomised controlled trials, and upcoming registries will soon collect observational data on the management of these diseases.
尽管临床试验数据显示了相互矛盾的结果，但可以考虑将甲氨蝶呤与 GC 联合用于治疗 GCA 和 PMR 患者。在上述 III 期研究之后，6-8 TCZ 已被批准用于 GCA 的治疗，该研究表明比安慰剂更高的缓解率和更好的 GC 保护。 5 值得注意的是，迄今为止，这两种药物均未与减少 GC 相关不良后果相关。对于 PMR，TCZ 在最近的 II/III 期试验中也非常有效，但尚未批准用于该疾病适应症。 9 10 由于 COVID-19 大流行，sarilumab 在 PMR 中的另一项 III 期试验提前终止。初步结果表明，在实现持续缓解方面，sarilumab 比安慰剂具有更高的疗效。 11 其他药物目前正在随机对照试验中进行测试，即将进行的注册将很快收集有关这些疾病管理的观察数据。

Along with these exciting developments, new unmet needs have emerged, including questions about the relevant treatment targets and outcomes in GCA and PMR. Other points of discussion are how the suppression of disease activity should be balanced against adverse consequences from drugs.12
随着这些令人兴奋的发展，新的未满足的需求也出现了，包括关于 GCA 和 PMR 的相关治疗目标和结果的问题。其他讨论要点是如何平衡疾病活动的抑制与药物的不良后果。 12

The treat-to-target (T2T) concept includes the definition of a specific treatment target, regular monitoring of the progress of therapy with respect to the treatment target and, if necessary, adjustment of therapy to achieve the lowest possible disease activity or remission. Treatment targets have already been defined in several areas of rheumatology, including rheumatoid arthritis (RA), spondyloarthritis (SpA), gout and systemic lupus erythematosus (SLE).13–17 Moreover, studies have demonstrated that a targeted management approach yields superior outcomes than conventional care in terms of clinical course, long-term damage and functional status.18–21
目标治疗（T2T）概念包括特定治疗目标的定义、针对治疗目标定期监测治疗进展，以及在必要时调整治疗以实现尽可能低的疾病活动或缓解。风湿病学的多个领域已经确定了治疗目标，包括类风湿性关节炎 (RA)、脊柱关节炎 (SpA)、痛风和系统性红斑狼疮 (SLE)。 13-17 此外，研究表明，在临床病程、长期损伤和功能状态方面，有针对性的管理方法比传统护理能产生更好的结果。 18-21日

Up to now, T2T is not a recognised treatment approach in GCA and PMR, and to this point there has not been a systematic evaluation and consensus finding process on this topic. The development of T2T recommendations for GCA/PMR, therefore, addresses a current unmet medical need.12
到目前为止，T2T 还不是 GCA 和 PMR 公认的治疗方法，并且到目前为止，还没有关于该主题的系统评估和共识寻找过程。因此，针对 GCA/PMR 的 T2T 建议的制定解决了当前未满足的医疗需求。 12

To address this gap, an international, multidisciplinary task force was formed to develop recommendations aimed at defining treatment targets for GCA and PMR, with the goal of improving the management of these diseases in clinical practice.
为了弥补这一差距，成立了一个国际多学科工作组，以制定旨在确定 GCA 和 PMR 治疗目标的建议，以改善临床实践中这些疾病的管理。

Methods 方法

The convenors (CDe and FB) and the methodologists (AK and DA) led a task force guided by the 2014 updated EULAR standardised operating procedures for developing recommendations.22 The 29 task force members consisted of rheumatologists, internists, a neuro-ophthalmologist, a patient representative, methodologists and a healthcare professional representing 10 countries. One face-to-face and one virtual meeting of the scientific committee (CDe, FB, ELM, MCC, PCG, AA, DA, AK, JSS, DC, LE, CDu, MW, LN, MB and EH), several virtual meetings of the steering committee (CDe, FB, DA, AK, MB and EH) and one face-to-face meeting of the entire task force took place. A nominal group technique was used for the virtual and the face-to-face meetings.
召集人（CDe 和 FB）和方法学家（AK 和 DA）领导了一个工作组，以 2014 年更新的 EULAR 标准化操作程序为指导，以制定建议。 22 工作组的 29 名成员包括来自 10 个国家的风湿病学家、内科医生、一名神经眼科医生、一名患者代表、方法学家和一名医疗保健专业人员。科学委员会 1 次面对面会议和 1 次虚拟会议（CDe、FB、ELM、MCC、PCG、AA、DA、AK、JSS、DC、LE、CDu、MW、LN、MB 和 EH）、数次虚拟会议召开了指导委员会（CDe、FB、DA、AK、MB 和 EH）会议以及整个工作组的一次面对面会议。虚拟会议和面对面会议均采用名义小组技术。

At the first (virtual) meeting, the scientific committee agreed on 11 key questions relevant to T2T in GCA and PMR (see online supplemental table 1). These key questions were transformed into the respective Population, Intervention, Comparator, Outcome question format, which served as the basis for the systematic literature review (SLR).
在第一次（虚拟）会议上，科学委员会就 GCA 和 PMR 中与 T2T 相关的 11 个关键问题达成了一致（参见在线补充表 1）。这些关键问题被转化为相应的人口、干预、比较、结果问题格式，作为系统文献综述（SLR）的基础。

Supplemental material 补充材料

A single SLR was conducted by four fellows (DC, LE, MB and EH) under the guidance of the methodologists. DC and LE conducted the screening and selection of articles. Data extraction, data synthesis and quality appraisal were performed by MB and EH.
一次 SLR 由四位研究员（DC、LE、MB 和 EH）在方法学家的指导下进行。 DC和LE进行了文章的筛选和选择。数据提取、数据合成和质量评价由MB和EH完成。

The search strategies were developed by an experienced librarian (LF) and a systematic search was conducted in MEDLINE, EMBASE and the Cochrane Library (initial search to March 2021, updated search through May 2022). Full research articles, short reports and letters of randomised controlled trials as well as prospective and retrospective studies including an intervention and control group were retrieved. Further inclusion criteria were sample size of >20 patients, publication in English or qualitative studies without a limit of participants and addressing any of the aspects raised by the key questions. Risk of bias (RoB) was assessed using the Cochrane RoB tool for randomised trials version 2, the RoB tool for non-randomised studies of Interventions and the appraisal tool for cross-sectional studies (AXIS).23–25
检索策略由经验丰富的图书馆员 (LF) 制定，并在 MEDLINE、EMBASE 和 Cochrane 图书馆进行系统检索（初始检索至 2021 年 3 月，更新检索至 2022 年 5 月）。检索了完整的研究文章、简短报告和随机对照试验信件以及包括干预组和对照组的前瞻性和回顾性研究。进一步的纳入标准是样本量大于 20 名患者、以英文发表或不限制参与者的定性研究，并解决关键问题提出的任何方面。使用用于随机试验版本 2 的 Cochrane RoB 工具、用于干预措施非随机研究的 RoB 工具以及用于横断面研究的评估工具 (AXIS) 来评估偏倚风险 (RoB)。 23–25

The evidence was presented during the second (face-to-face) meeting of the scientific committee and the task force in June 2022. The data presented at this meeting were synthesised in a separate manuscript, describing the SLR in detail, providing the scientific evidence base for the present manuscript. (Hysa et al, manuscript in preparation)
这些证据是在 2022 年 6 月举行的科学委员会和工作组第二次（面对面）会议上提出的。本次会议上提出的数据综合在一份单独的手稿中，详细描述了 SLR，提供了科学证据本手稿的基础。 （Hysa 等人，手稿正在准备中）

At this second meeting of the scientific committee, the evidence was discussed, and based on the initial clinical key questions and the evidence, four proposals for overarching principles and five specific recommendations were prepared. Subsequently, the entire task force discussed the evidence again and refined and complemented the statements. This was followed by voting on the individual statements. Consensus was accepted if ≥75% of the members voted in favour of the statement at the first round of discussion, ≥67% at the second round, and at a third round >50% was accepted.26 The Oxford Centre for Evidence-based Medicine 2011 levels of evidence (LoE) derived from the SLR were added to each recommendation.27
在科学委员会的第二次会议上，对证据进行了讨论，并根据最初的临床关键问题和证据，制定了四项总体原则提案和五项具体建议。随后，专案组全体人员再次对证据进行讨论，对陈述进行细化和补充。随后对个人陈述进行投票。如果在第一轮讨论中≥75%的成员投票赞成该声明，在第二轮讨论中≥67%的成员投票赞成该声明，则在第三轮讨论中>50%的成员投票赞成该声明，则视为达成共识。 26 牛津循证医学中心 2011 年源自 SLR 的证据水平 (LoE) 被添加到每项建议中。 27

After the task force meeting, each member anonymously indicated their level of agreement (LoA) via Survey Monkey. (LoA, 0–10 numeric rating scale ranging from 0= ‘completely disagree’ to 10= ‘completely agree’). The mean and SD of the LoA, as well as the percentage of task force members with an agreement ≥8 are presented. Based on the gaps in evidence and controversial points, a research agenda was formulated.
工作组会议结束后，每位成员通过 Survey Monkey 匿名表示他们的同意程度 (LoA)。 （LoA，0-10 数字评分量表，范围从 0=“完全不同意”到 10=“完全同意”）。给出了 LoA 的平均值和标准差，以及协议≥8 的工作组成员的百分比。根据证据差距和争议点，制定了研究议程。

Results 结果

General aspects 一般方面

These T2T recommendations are intended to advise primary, secondary and tertiary care physicians (including general practitioners, rheumatologists, ophthalmologists, neurologists, geriatricians as well as specialists in internal or vascular medicine, radiology and vascular surgery), health professionals in rheumatology, pharmacists, patient organisations, payers, hospital managers and trial investigators.
这些 T2T 建议旨在为初级、二级和三级护理医生（包括全科医生、风湿病学家、眼科医生、神经科医生、老年科医生以及内科或血管医学、放射学和血管外科专家）、风湿病学卫生专业人员、药剂师、患者提供建议。组织、付款人、医院管理者和试验研究者。

The target population are people with GCA, PMR and GCA/PMR.
目标人群是 GCA、PMR 和 GCA/PMR 患者。

These recommendations provide a strategic management concept for GCA and PMR, but are not intended to cover all management aspects of these diseases. They should be understood as complementary to the current international treatment recommendations.6–8
这些建议为 GCA 和 PMR 提供了战略管理概念，但并不旨在涵盖这些疾病的所有管理方面。它们应被理解为对当前国际治疗建议的补充。 6-8

A total of five overarching principles and six specific recommendations were formulated. These are summarised in table 1 (including the LoE and LoA) and are discussed in detail below.
共制定了五项总体原则和六项具体建议。表 1 总结了这些内容（包括 LoE 和 LoA），并在下面详细讨论。

View this table:
Table 1 表1

Treat-to-Target (T2T) recommendations in giant cell arteritis (GCA) and polymyalgia rheumatica (PMR)
巨细胞动脉炎 (GCA) 和风湿性多肌痛 (PMR) 的目标治疗 (T2T) 建议

Overarching principles 总体原则

These statements refer to principles of a generic and self-evident nature. They are, therefore, not necessarily based on specific LoE but reflect issues of good clinical practice. The task force considered them as a framework for the subsequent, specific recommendations.
这些陈述涉及一般性和不言而喻的原则。因此，它们不一定基于特定的 LoE，而是反映良好临床实践的问题。工作组将其视为后续具体建议的框架。

  1. Clinical management of GCA and PMR should be driven by the awareness that they are closely interrelated conditions in a common spectrum of inflammatory diseases and can occur separately, simultaneously or in temporal sequence to each other.
    GCA 和 PMR 的临床管理应基于以下认识：它们是常见炎症性疾病中密切相关的病症，并且可以单独、同时或按时间顺序发生。

GCA and PMR are interlinked conditions that frequently overlap.3 PMR often occurs as a symptom of relapse in GCA28; therefore, it is possible that people with PMR who have recurrent relapses, as well as those who are unable to taper GCs, have underlying GCA that was ‘masked’ at the time of diagnosis. Moreover, there is evidence of subclinical vasculitis in some people with PMR, however, the significance of this observation for clinical outcomes is still unclear.29–31
GCA 和 PMR 是相互关联且经常重叠的条件。 3 PMR 经常作为 GCA 复发的症状出现 28；因此，反复复发的 PMR 患者以及无法逐渐减少 GC 的患者可能患有在诊断时被“掩盖”的潜在 GCA。此外，有证据表明一些 PMR 患者存在亚临床血管炎，但这一观察结果对临床结果的意义仍不清楚。 29–31

In current practice, PMR is mainly treated by primary care physicians, whereas people with GCA are commonly referred to secondary/tertiary care specialists.32 33 Shared care between specialists and primary care physicians for both diseases is desirable, with regular evaluation of patients by an expert, particularly in case of difficult to treat PMR. This should ensure the early recognition of a possible GCA/PMR overlap and the management of both diseases according to a T2T strategy.
在目前的实践中，PMR 主要由初级保健医生治疗，而 GCA 患者通常被转介给二级/三级保健专家。 32 33 对于这两种疾病，专家和初级保健医生之间的共同护理是可取的，由专家对患者进行定期评估，特别是在难以治疗的 PMR 情况下。这应确保尽早识别可能的 GCA/PMR 重叠，并根据 T2T 策略管理这两种疾病。

  1. GCA is a medical emergency because of the imminent risk of sight loss and other ischaemic events and, therefore, requires immediate treatment; management usually requires multidisciplinary collaboration.
    GCA 是一种医疗紧急情况，因为存在视力丧失和其他缺血事件的迫在眉睫的风险，因此需要立即治疗；管理通常需要多学科协作。

This statement emphasises the need for early treatment of GCA, particularly in case of cranial manifestations (such as headache, jaw claudication and visual symptoms), given that sight loss occurs in 15%–35% of patients.4 34 35 This complication has a dramatic impact on the quality of life of patients and their caregivers.36 If one eye is affected, the risk for losing the second eye is as high as 50%.37 38 Sight loss almost exclusively occurs before the initiation of GC therapy; the risk for visual impairment is reduced dramatically once patients are on treatment.34 35
该声明强调了 GCA 早期治疗的必要性，特别是在出现颅部症状（例如头痛、下颌跛行和视觉症状）的情况下，因为 15%–35% 的患者会出现视力丧失。 4 34 35 这种并发症对患者及其护理人员的生活质量产生巨大影响。 36 如果一只眼睛受到影响，失去第二只眼睛的风险高达 50%。 37 38 视力丧失几乎全部发生在开始 GC 治疗之前；一旦患者接受治疗，视力障碍的风险就会大大降低。 34 35

Immediate treatment of GCA implies that the diagnosis is also confirmed rapidly. Treatment of a person with high suspicion for GCA should not be delayed because of pending diagnostic procedures.39 ‘Fast-track’ GCA clinics have facilitated rapid diagnosis and specialist care,34 35 40–43 and have helped to increase the awareness about the disease among referrers, thus further reducing the symptom to therapy lag.33
GCA 的立即治疗意味着诊断也能得到迅速确诊。对于高度怀疑患有 GCA 的人，不应因未完成的诊断程序而延迟治疗。 39 “快速通道”GCA 诊所促进了快速诊断和专科护理，34 35 40-43 并有助于提高转介者对该疾病的认识，从而进一步减少症状与治疗的滞后。 33

People with GCA may present with different symptoms. This is the leading reason why they are often seen by a variety of specialists, and explains why a multidisciplinary collaboration is needed for a T2T strategy in this disease. Further, GCA may cause damage in different vascular territories potentially leading to sight loss, strokes, tongue or scalp necrosis, as well as peripheral limb ischaemia, requiring multidisciplinary management including ophthalmologists, neurologists and plastic and vascular surgeons.3
GCA 患者可能会出现不同的症状。这是为什么它们经常被不同的专家看诊的主要原因，并解释了为什么这种疾病的 T2T 策略需要多学科合作。此外，GCA 可能对不同的血管区域造成损害，可能导致视力丧失、中风、舌头或头皮坏死以及周围肢体缺血，需要包括眼科医生、神经科医生以及整形和血管外科医生在内的多学科治疗。 3

  1. Patients should be offered access to information about GCA and PMR, including clinical disease features, patient-reported outcomes, potential complications, treatment-related benefits and risks, as well as relevant comorbidities.
    应向患者提供有关 GCA 和 PMR 的信息，包括临床疾病特征、患者报告的结果、潜在并发症、治疗相关的获益和风险以及相关合并症。

Information about GCA and PMR needs to be accessible to all patients and caregivers. Because GCA and PMR commonly overlap, all patients should receive information on both diseases. Most people with GCA and PMR respond quickly to GC therapy and, therefore, some of them may prematurely stop treatment in the assumption that they are cured. This results not only in a rapid return of symptoms, but also bears the risk of tissue ischaemia.44 45 Patients also need to be informed that up to 60% of them will have one or more relapses during GC tapering, and that a relapse might lead to ischaemic complications.46 47
所有患者和护理人员都需要能够获取有关 GCA 和 PMR 的信息。由于 GCA 和 PMR 通常重叠，因此所有患者都应获得有关这两种疾病的信息。大多数患有 GCA 和 PMR 的人对 GC 治疗反应很快，因此，他们中的一些人可能会在假设自己已治愈的情况下过早停止治疗。这不仅会导致症状快速复发，而且还会带来组织缺血的风险。 44 45 患者还需要被告知，高达 60% 的患者在 GC 减量期间会出现一次或多次复发，并且复发可能会导致缺血性并发症。 46 47

Patient awareness should also be directed to understand the distinctions between disease-related and disease-unrelated symptoms. For example, shoulder pain in PMR might be due to a relapse or unrelated to PMR, such as osteoarthritis, adhesive capsulitis or rotator cuff disease. Fatigue can be either a symptom of GCA and PMR, caused by other conditions or due to treatment.48 Likewise, increment of acute phase reactants does not always reflect active GCA/PMR but can be related to infections or other inflammatory conditions. Relapses may also be present despite normal erythrocyte sedimentation rate (ESR) and C reactive protein (CRP), particularly, but not only, in people who are treated with interleukin-6 receptor (IL-6R) blocking agents.49 People with GCA should further be informed that certain manifestations such as vision loss can be related to active disease (when new or worsened, occurring in one-fifth of cases with a major relapse),50 to damage (when persistent in spite of treatment and with no other sign of active disease) or to other conditions (eg, age-related macular degeneration, glaucoma or cataracts). Patients should also be educated about possible adverse consequences of therapy and taught to recognise them.51
还应引导患者意识到疾病相关症状和疾病无关症状之间的区别。例如，PMR 中的肩部疼痛可能是由于复发或与 PMR 无关，例如骨关节炎、粘连性囊炎或肩袖疾病。疲劳可能是 GCA 和 PMR 的症状，由其他疾病或治疗引起。 48 同样，急性期反应物的增加并不总是反映活跃的 GCA/PMR，但可能与感染或其他炎症状况有关。尽管红细胞沉降率 (ESR) 和 C 反应蛋白 (CRP) 正常，但也可能出现复发，尤其是但不仅限于接受白细胞介素 6 受体 (IL-6R) 阻断剂治疗的患者。 49 应进一步告知患有 GCA 的人，某些表现，例如视力丧失，可能与活动性疾病有关（当新发或恶化时，发生在五分之一的严重复发病例中），50 与损害有关（当尽管治疗但持续存在时）并且没有其他活动性疾病迹象）或其他病症（例如，年龄相关性黄斑变性、青光眼或白内障）。还应教育患者了解治疗可能产生的不良后果，并教会他们认识到这些后果。 51

Patients should receive information about comorbidities. The term ‘relevant’ was chosen to express that rheumatologists are trained to focus on those that are relevant to the disease and/or to its treatment, such as osteoporosis, diabetes mellitus or cardiovascular disease, while general medical concerns are addressed by their primary and other specialty care physicians as appropriate.52 53
患者应该收到有关合并症的信息。选择“相关”一词是为了表达风湿病学家接受过培训，专注于与疾病和/或其治疗相关的疾病，例如骨质疏松症、糖尿病或心血管疾病，而一般医疗问题则通过其主要和/或治疗来解决。其他适当的专科护理医生。 52 53

The best method of providing information and the amount of information that should be delivered to patients is likely dependent on patient-specific preferences. The foundation for disease education is the medical consultation, and may be complemented by specific training programmes of healthcare professionals, patient charities, online, print or video material, as well as via telemedicine.54
提供信息的最佳方法以及应向患者提供的信息量可能取决于患者的具体偏好。疾病教育的基础是医疗咨询，并可以通过医疗保健专业人员、患者慈善机构、在线、印刷或视频材料以及远程医疗的具体培训计划来补充。 54

  1. Management of GCA and PMR should be based on shared decision making between the informed patient and the physician.
    GCA 和 PMR 的管理应基于知情的患者和医生之间的共同决策。

The vast majority of patients with GCA and PMR accept initial treatment given the sudden onset of symptoms and their significant impact on quality of life and daily activities. Once remission is achieved, ‘coming off glucocorticoids’ and ‘living with glucocorticoids’ become important aspects of the ongoing care for patients.55 The maintenance of the target must, therefore, be discussed in light of emerging adverse consequences of treatment, particularly in the long term. Similarly, the possible advantages and disadvantages of different drugs and routes of administration need to be discussed with patients on an individual basis.
鉴于症状突然出现及其对生活质量和日常活动的重大影响，绝大多数 GCA 和 PMR 患者接受初步治疗。一旦实现缓解，“停用糖皮质激素”和“与糖皮质激素一起生活”就成为患者持续护理的重要方面。 55 因此，必须根据治疗新出现的不良后果（尤其是长期的不良后果）来讨论维持目标的问题。同样，不同药物和给药途径可能的优点和缺点也需要与患者进行个体化讨论。

  1. Treatment of GCA and PMR should aim at maximising health-related quality of life through control of symptoms, preventing disease-related damage and minimising treatment-related adverse consequences, taking relevant comorbidities into account.
    GCA 和 PMR 的治疗应旨在通过控制症状、预防疾病相关损害和尽量减少治疗相关不良后果，同时考虑到相关合并症，最大限度地提高与健康相关的生活质量。

The goal of maintaining health-related quality of life is common to several T2T recommendations, an outcome regarded as the highest value for patients.13–15 Mortality is not increased in PMR,56 57 whereas in GCA, patients have higher mortality, particularly at disease onset, most likely as a consequence of disease manifestations and adverse effects of intensive treatment.58
维持与健康相关的生活质量的目标是多项 T2T 建议的共同目标，这一结果被认为对患者来说具有最高价值。 13–15 PMR 的死亡率没有增加，56 57 而 GCA 的患者死亡率较高，特别是在疾病发作时，很可能是由于疾病表现和强化治疗的不良反应造成的。 58

Among disease-related symptoms, patients pay particular attention to pain, stiffness, disability and fatigue.48 59 In GCA, preservation of sight and integrity of other tissues potentially affected by vascular compromise are other fundamental aspects of maintaining a high quality of life.36 Side effects from treatment, such as weight gain, bruising, skin atrophy, diabetes, infections, mood changes and muscle weakness, might gradually reduce the gains of quality of life achieved in early stages of disease management through suppression of inflammation.51 60 Negative adverse consequences from treatment unfortunately cannot always be avoided, but should be minimised. Preventing overtreatment of GCA and PMR with GC, due to starting or maintenance dosages that are excessively high or for a period of time that is too long or by not considering GC sparing agents is an important additional goal. Even though several drugs may help to reduce the cumulative GC dose in both GCA and PMR, so far none have been proven to reduce GC-related adverse outcomes.5 9 10 61 62 Common comorbidities such as osteoporosis, diabetes or cardiovascular disease also need to be considered, especially those that may be worsened by treatment and negatively impact health-related quality of life.52 53
在疾病相关症状中，患者特别关注疼痛、僵硬、残疾和疲劳。 48 59 在 GCA 中，保护视力和可能受血管损害影响的其他组织的完整性是维持高质量生活的其他基本方面。 36 治疗产生的副作用，例如体重增加、瘀伤、皮肤萎缩、糖尿病、感染、情绪变化和肌肉无力，可能会逐渐降低通过抑制炎症进行疾病管理的早期阶段所取得的生活质量改善。 51 60 不幸的是，治疗带来的负面不良后果无法总是避免，但应尽量减少。防止由于起始或维持剂量过高或持续时间过长或不考虑 GC 保留剂而对 GCA 和 PMR 进行 GC 过度治疗是一个重要的额外目标。尽管有几种药物可能有助于减少 GCA 和 PMR 中的累积 GC 剂量，但迄今为止还没有一种药物被证明可以减少 GC 相关的不良后果。 5 9 10 61 62 还需要考虑骨质疏松症、糖尿病或心血管疾病等常见合并症，尤其是那些可能因治疗而恶化并对健康相关生活质量产生负面影响的合并症。 52 53

Specific recommendations 具体建议

Recommendation 1 建议1

The treatment target of GCA and PMR should be remission; remission is the absence of clinical symptoms and systemic inflammation.
GCA和PMR的治疗目标应该是缓解；缓解是指没有临床症状和全身炎症。

This treatment target is similar to that of other T2T recommendations in rheumatology,13–15 and frequently serves as an outcome in clinical trials and observational studies of GCA and PMR.12 63 (Hysa et al, manuscript in preparation) The LoA was high, even though there was no evidence that remission performed better than any other treatment target (eg, absence of relapse, cumulative GC dose). (Hysa et al, manuscript in preparation) Remission is normally achieved rapidly with GC therapy, although a proportion of patients may be refractory and achieve only incomplete disease control.64 65 The definition of an instrument to determine remission in GCA and PMR was beyond the scope of this project and is the subject of ongoing research. Several proposals to define remission have been made by international study groups and investigators of clinical trials. They most commonly include the absence of clinical symptoms related to GCA and/or PMR and the normalisation of acute phase reactants, particularly ESR and CRP.12 63 The task force stipulated the term ‘absence of systemic inflammation’ to potentially also include other markers of disease activity such as imaging. While the role of imaging as an outcome variable or component of remission is still unclear, there is the increasing evidence that, at least in GCA, imaging-determined signs of activity might have an impact on future relapses and vascular damage.66–68 The present statement, however, should not be understood as a recommendation to reach imaging remission and/or negative acute phase reactants at all costs, rather the achievement of the target should be balanced against the potential burden from treatment-related adverse events.
该治疗目标与风湿病学中其他 T2T 建议的治疗目标类似，13-15，并且经常作为 GCA 和 PMR 临床试验和观察性研究的结果。 12 63（Hysa 等人，手稿正在准备中）LoA 很高，尽管没有证据表明缓解效果优于任何其他治疗目标（例如，没有复发、累积 GC 剂量）。 （Hysa 等人，手稿正在准备中）GC 治疗通常可以迅速实现缓解，尽管一部分患者可能难以治疗并且只能实现不完全的疾病控制。 64 65 确定 GCA 和 PMR 缓解的工具的定义超出了本项目的范围，是正在进行的研究的主题。国际研究小组和临床试验研究者已经提出了一些定义缓解的建议。它们最常见的包括不存在与 GCA 和/或 PMR 相关的临床症状以及急性期反应物（特别是 ESR 和 CRP）的正常化。 12 63工作组规定“不存在全身炎症”这一术语还可能包括其他疾病活动标志物，例如影像学。虽然影像学作为结果变量或缓解组成部分的作用尚不清楚，但越来越多的证据表明，至少在 GCA 中，影像学确定的活动迹象可能会对未来的复发和血管损伤产生影响。 66-68 然而，本声明不应被理解为不惜一切代价实现影像学缓解和/或阴性急性期反应物的建议，而是应在目标的实现与治疗相关不良事件的潜在负担之间取得平衡。

Alternative treatment targets (such as low-disease activity in RA) need to be investigated further in PMR and GCA,10 12 hence, this topic has been added to the research agenda.
替代治疗目标（例如 RA 的低疾病活动度）需要在 PMR 和 GCA 中进一步研究，10 12 因此，该主题已添加到研究议程中。

Recommendation 2 建议2

Treatment of GCA should also aim to prevent tissue ischemia and vascular damage.
GCA 的治疗还应旨在防止组织缺血和血管损伤。

The prevention of tissue ischaemia and vascular damage was added as a specific treatment target even though this topic has been included in the overarching principles. There was some discussion among the task force whether the ‘maintenance of tissue and vascular integrity’ would be the more adequate target. However, the group ultimately came to the conclusion that this might be a too ambitious goal, given that, in an older patient population there might be several other factors not directly related to GCA such as atherosclerosis threatening the ‘integrity’ of organs and vessels. The clear objective in the management of GCA is the prevention of the sequelae from disease and long-term treatment.36
尽管组织缺血和血管损伤的预防已包含在总体原则中，但该主题仍被添加为具体的治疗目标。工作组内部进行了一些讨论，讨论“维持组织和血管完整性”是否是更合适的目标。然而，该小组最终得出的结论是，这可能是一个过于雄心勃勃的目标，因为在老年患者群体中，可能存在与 GCA 不直接相关的其他几个因素，例如威胁器官和血管“完整性”的动脉粥样硬化。 GCA 治疗的明确目标是预防疾病后遗症和长期治疗。 36

Prevention of vascular damage should, therefore, not only be understood as prevention of damage from GCA (eg, aortic aneurysms) but also as a prevention of macrovascular and microvascular damage associated with long-term GC therapy.69–71 In this context, it is important to understand that progression of vascular damage, particularly aortic aneurysms, may also occur in patients in persistent clinical remission.72 The pathogenic mechanisms triggering the progression of vessel wall destruction, as well as the possibilities to prevent, or at least halt these changes, require further study.
因此，预防血管损伤不仅应理解为预防GCA（例如主动脉瘤）造成的损伤，还应理解为预防与长期GC治疗相关的大血管和微血管损伤。 69-71 在这种情况下，重要的是要了解血管损伤的进展，特别是主动脉瘤，也可能发生在持续临床缓解的患者中。 72 触发血管壁破坏进展的致病机制，以及预防或至少阻止这些变化的可能性，需要进一步研究。

Recommendation 3 建议3

Treatment selection in GCA and PMR should be based on disease severity and activity, presence of relevant comorbidities and potential predictors of outcome; treatment should be modified as needed during follow-up.
GCA 和 PMR 的治疗选择应基于疾病的严重程度和活动性、相关合并症的存在以及结果的潜在预测因素；随访期间应根据需要修改治疗方案。

Specific recommendations on the selection of individual medications or drug dosages have been made elsewhere and are not subject of the present work.6–8 The task force acknowledged that several factors in addition to disease activity need to be considered in balancing treatment benefits against risks. A person with GCA suffering from visual symptoms, jaw claudication or other ischaemic manifestations may be considered to have more ‘severe’ disease than a patient with predominantly systemic symptoms without evidence of tissue or vascular damage (eg, PMR or constitutional symptoms only). Consequently, the former patient may require more intensive initial treatment than the latter. In patients without organ threatening manifestations, balanced decision making should take into account comorbidities, as well as predictors of disease outcomes that may influence the choice of therapy. The ACR/EULAR recommendations for PMR management list female sex, high acute phase reactants and peripheral arthritis as associated with an increased risk of relapse, and patients with these features warrant more intensive and longer treatment.7 62 In GCA, patients with a high level of systemic inflammation at baseline, persistently increased inflammatory markers or imaging signs of inflammation, as well as those with predominant extracranial disease, tend to relapse more frequently than patients without these factors.67 73 Hence, these patients may benefit in particular from early administration of GC sparing agents.
关于选择个别药物或药物剂量的具体建议已在其他地方提出，不是本工作的主题。 6-8 特别工作组承认，在平衡治疗效益与风险时，除了疾病活动之外，还需要考虑几个因素。患有视觉症状、下颌跛行或其他缺血表现的 GCA 患者可能被认为比以全身症状为主但没有组织或血管损伤证据（例如，PMR 或仅全身症状）的患者患有更“严重”的疾病。因此，前一种患者可能需要比后者更强化的初始治疗。对于没有器官威胁表现的患者，平衡决策应考虑合并症以及可能影响治疗选择的疾病结果的预测因素。 ACR/EULAR 针对 PMR 管理的建议列出了女性、高急性期反应物和外周关节炎与复发风险增加相关，具有这些特征的患者需要更强化和更长时间的治疗。 7 62 在 GCA 中，基线时全身炎症水平较高、炎症标志物或炎症影像学征象持续升高的患者，以及颅外疾病占主导地位的患者，往往比没有这些因素的患者更容易复发。 67 73 因此，这些患者可能特别受益于早期给予 GC 保留药物。

Assessing benefit versus risks of treatments should be performed continuously during the follow-up. While disease activity and severity might be the main drivers of treatment choice at disease outset, therapy-related side effects, comorbidities and predictors of outcome may play a more important role later in the disease course.51
在随访期间应持续评估治疗的获益与风险。虽然疾病活动性和严重程度可能是疾病开始时治疗选择的主要驱动因素，但与治疗相关的副作用、合并症和结果预测因素可能在病程后期发挥更重要的作用。 51

Recommendation 4 建议4

Comorbidities may influence the assessment of the treatment target and should be considered before modifying treatment.
合并症可能会影响治疗目标的评估，在修改治疗之前应予以考虑。

Both rheumatic (eg, rotator cuff disease, osteoarthritis of the shoulder or cervical spine, fibromyalgia) and non-rheumatic (eg, Parkinson’s disease) causes of pain and stiffness influence the assessment of disease activity in PMR, particularly when clinical composite scores are used that may also be affected by these conditions.74 In GCA, other causes of headache (eg, migraine, trigeminal neuralgia, tension headache) or visual disturbances need to be distinguished from GCA-related symptoms. Acute phase reactants are certainly helpful in these situations, but when patients are treated with IL-6 blocking agents, other markers of systemic inflammation need to be identified that help to better interpret patients’ symptoms.4 12 This aspect has been added to the research agenda.
引起疼痛和僵硬的风湿性（例如肩袖疾病、肩部或颈椎骨关节炎、纤维肌痛）和非风湿性（例如帕金森病）都会影响 PMR 中疾病活动性的评估，特别是在使用临床综合评分时也可能受到这些条件的影响。 74 在 GCA 中，头痛（例如偏头痛、三叉神经痛、紧张性头痛）或视觉障碍的其他原因需要与 GCA 相关症状区分开来。急性期反应物在这些情况下当然有帮助，但当患者接受 IL-6 阻断剂治疗时，需要确定全身炎症的其他标志物，以帮助更好地解释患者的症状。 4 12 这方面已被添加到研究议程中。

Recommendation 5 建议5

Once remission is reached, it should be maintained with the minimal effective dose of medication; drug-free remission may be achieved in a proportion of patients.
一旦达到缓解，应以最小有效剂量的药物维持；部分患者可以实现无药物缓解。

The task force discussed whether the maintenance of remission, or rather, the prevention of a relapse should be the preferred treatment target. A relapse is often defined as reappearance of clinical symptoms and systemic inflammation that requires intensification of therapy.12 63 However, patients with non-specific symptoms or increased inflammatory markers without another explanation than GCA or PMR are in a disease state that is neither remission nor relapse. The task force voted for the maintenance of remission as a relevant target in T2T assuming that patients would benefit in the long term by a better quality of life and prevention of vascular damage. The SLR, however, retrieved no evidence on this aspect of disease management, and therefore, this topic has been added to the research agenda. (Hysa et al, manuscript in preparation)
工作组讨论了维持缓解，或者更确切地说，预防复发是否应该成为首选治​​疗目标。复发通常被定义为临床症状和全身炎症的再次出现，需要强化治疗。 12 63 然而，具有非特异性症状或炎症标记物升高且没有 GCA 或 PMR 之外的其他解释的患者处于既没有缓解也没有复发的疾病状态。该工作组投票支持将维持缓解作为 T2T 的相关目标，认为患者将通过更好的生活质量和预防血管损伤而长期受益。然而，SLR 没有检索到有关疾病管理这方面的证据，因此，该主题已被添加到研究议程中。 （Hysa 等人，手稿正在准备中）

The task force further emphasised that patients should not be pushed to taper-off medication too quickly, a strategy that often results in relapse of disease. At the same time, the task force recognised that overtreatment should also be avoided. Achieving the minimal effective dose of medication is an important goal, and tapering-off GCs may have a higher priority than discontinuing disease modifying antirheumatic drugs (DMARDs), if both drugs are used in combination. However, no study has yet compared the benefits and risks of low-dose GCs (≤7.5 mg prednisone equivalent per day)75 without DMARDs against DMARDs without GCs.
该工作组进一步强调，不应强迫患者过快地减少用药，这种策略往往会导致疾病复发。与此同时，工作组认识到还应避免过度治疗。实现最小有效药物剂量是一个重要目标，如果两种药物联合使用，逐渐减少 GC 可能比停用疾病缓解抗风湿药物 (DMARD) 具有更高的优先级。然而，尚无研究比较不含 DMARD 的低剂量 GC（每天≤7.5 毫克强的松当量）75 与不含 GC 的 DMARD 的益处和风险。

In a proportion of patients, drug-free remission may be achieved. In a trial of TCZ in GCA (GIACTA), for example, 22% of patients initially randomised to TCZ reached sustained drug-free remission after 156 weeks,76 whereas in PMR, observational studies suggest that long-term drug-free remission can be achieved in 30%–60% of patients.77–79 Tapering off treatment should always be balanced against the risk of worsening disease activity.5 46 47
部分患者可以实现无药物缓解。例如，在 GCA 中的 TCZ 试验 (GIACTA) 中，最初随机接受 TCZ 的患者中有 22% 在 156 周后达到持续无药缓解，76 而在 PMR 中，观察性研究表明，长期无药缓解可通过30%–60% 的患者实现了这一目标。 77–79 逐渐减少治疗应始终与疾病活动恶化的风险相平衡。 5 46 47

Recommendation 6 建议6

Disease activity in GCA and PMR should be monitored regularly, as frequently as every 1–4 weeks until remission has been achieved, and at longer monitoring intervals (eg, between 3 and 6 months) in patients in stable remission on therapy; monitoring of patients off therapy should be discussed on an individual basis.
应定期监测 GCA 和 PMR 的疾病活动，频率为每 1-4 周一次，直至达到缓解，对于治疗稳定缓解的患者，监测间隔较长（例如 3 至 6 个月）；治疗结束后对患者的监测应根据个体情况进行讨论。

This recommendation is fully based on expert opinion given that evidence regarding monitoring intervals is absent. The monitoring timepoints recommended by the task force are more frequent than those suggested by the 2018 EULAR management recommendations for GCA and the 2015 ACR/EULAR management recommendations for PMR.6 7 The task force was of the opinion that both new patients and patients with relapse should be monitored very closely to document therapeutic response, exclude disease mimics and to identify those with refractory disease in order to discuss possible treatment alternatives. The task force members made the experience that lack of resources is an important obstacle for a close follow-up of patients; however, this might be overcome by shared care between general practitioners and rheumatologists.
鉴于缺乏有关监测间隔的证据，该建议完全基于专家意见。工作组建议的监测时间点比 2018 年 EULAR 针对 GCA 的管理建议和 2015 年 ACR/EULAR 针对 PMR 的管理建议建议的监测时间点更为频繁。 6 7 该工作组认为，应非常密切地监测新患者和复发患者，以记录治疗反应，排除疾病模拟并识别患有难治性疾病的患者，以便讨论可能的治疗方案。工作组成员体会到，资源匮乏是对患者进行密切随访的重要障碍；然而，全科医生和风湿病学家之间的共同护理可能会克服这个问题。

Once stable remission has been achieved, monitoring intervals may become longer; however, disease activity and particularly adverse consequences of treatment should be checked regularly. Whether all follow-up visits need to be face to face or can be replaced by telemedicine visits are issues that future research needs to clarify.
一旦达到稳定缓解，监测间隔可能会变长；然而，应定期检查疾病活动性，特别是治疗的不良后果。所有随访是否需要面对面或可以由远程医疗就诊取代，是未来研究需要澄清的问题。

On successful discontinuation of therapy, people with PMR may be followed up in primary care only (on demand). In GCA, regular specialist visits (even at longer intervals) are advised since aortic aneurysms may occur even years after quiescent disease.80 81 No consensus was found for monitoring the progression of vascular damage, therefore, this topic has been included in the research agenda.
成功停止治疗后，PMR 患者可能仅在初级保健中接受随访（按需）。在 GCA 中，建议定期进行专科就诊（甚至间隔较长），因为主动脉瘤甚至可能在疾病静止期数年后发生。 80 81 对于监测血管损伤的进展尚未达成共识，因此该课题已列入研究议程。

Based on the discussions and the areas of uncertainty, a research agenda has been proposed, delineated in box 1.
根据讨论和不确定性领域，提出了研究议程，如方框 1 所示。

Box 1 盒子1

Research agenda 研究议程

  • To develop evidence-based definitions of response, remission and relapse for GCA and PMR.
    制定 GCA 和 PMR 的缓解、缓解和复发的循证定义。

  • To develop a definition of refractory disease.
    制定难治性疾病的定义。

  • To develop a definition of vascular damage.
    制定血管损伤的定义。

  • To work-out tools to adequately assess disease activity, disease activity states, patient-reported outcomes (including fatigue, health-related quality of life) and a health assessment questionnaire specific for GCA and PMR.
    制定工具来充分评估疾病活动、疾病活动状态、患者报告的结果（包括疲劳、与健康相关的生活质量）以及针对 GCA 和 PMR 的健康评估问卷。

  • To conduct a study to compare a T2T strategy in GCA and PMR with conventional care.
    开展一项研究，将 GCA 和 PMR 中的 T2T 策略与传统护理进行比较。

  • To study whether the maintenance of remission is an equivalent treatment target to the prevention of relapse(s).
    研究维持缓解是否是与预防复发同等的治疗目标。

  • To assess the role of imaging as a treatment target and to investigate the significance of ongoing imaging signs of inflammation in patients in clinical remission.
    评估影像学作为治疗目标的作用，并研究临床缓解患者炎症持续影像学征象的意义。

  • To study the phenotype and outcome of people with PMR presenting with subclinical vasculitis.
    研究表现为亚临床血管炎的 PMR 患者的表型和结果。

  • To identify predictors of treatment response, damage, prognosis and course of disease, including the identification of genomic/proteomic predictors from blood and tissue.
    确定治疗反应、损伤、预后和病程的预测因子，包括从血液和组织中鉴定基因组/蛋白质组预测因子。

  • To collect data on long-term follow-up, including imaging and laboratory data of people with GCA and/or PMR.
    收集长期随访数据，包括 GCA 和/或 PMR 患者的影像学和实验室数据。

  • To study the best imaging modality for early detection and monitoring of vascular damage.
    研究早期检测和监测血管损伤的最佳成像方式。

  • To define low disease activity in PMR and GCA and assess its value as an alternative treatment target.
    定义 PMR 和 GCA 的低疾病活动度并评估其作为替代治疗目标的价值。

  • To study the outcome of patients with persistently low disease activity (eg, low-grade vascular inflammation or slight elevation of acute phase reactants without another explanation) concerning long-term outcomes (damage and comorbidities).
    研究疾病活动度持续较低的患者（例如，低度血管炎症或急性期反应物轻微升高，无其他解释）有关长期结果（损伤和合并症）的结果。

  • To compare the outcomes of patients with low disease activity without treatment versus patients in remission on long-term low-dose therapy.
    比较未经治疗的低疾病活动性患者与长期低剂量治疗缓解的患者的结果。

  • To study whether use of glucocorticoid (GC) sparing agents leads to a reduction in GC-related adverse outcomes.
    研究使用糖皮质激素 (GC) 节约药物是否可以减少 GC 相关不良后果。

  • To assess when and in whom treatments can be stopped once remission is achieved.
    评估一旦达到缓解，何时以及哪些人可以停止治疗。

  • To investigate the relationship between patient-reported outcomes and disease activity in GCA and PMR.
    调查 GCA 和 PMR 患者报告的结果与疾病活动度之间的关系。

  • To investigate the progression of structural damage using different treatments.
    研究使用不同处理方法的结构损伤的进展情况。

  • To define intervals and methods to monitor structural damage in GCA.
    定义监测 GCA 结构损坏的时间间隔和方法。

  • To study the temporal evolution of vascular damage in GCA: how quickly does damage occur; what are the effects of aortic involvement early in the disease as compared with (new) involvement in later stages?
    研究 GCA 血管损伤的时间演变：损伤发生的速度有多快；与疾病后期（新的）主动脉受累相比，疾病早期受累主动脉有何影响？

  • To investigate the role of telemedicine as a tool for T2T in PMR/GCA.
    研究远程医疗作为 T2T 工具在 PMR/GCA 中的作用。

  • To study different treatment strategies and their effect on mortality in GCA.
    研究不同的治疗策略及其对 GCA 死亡率的影响。

  • To investigate the difference between long-term remission and cure of disease.
    探讨疾病长期缓解和治愈之间的差异。

  • To test the cost-effectiveness of a T2T strategy in GCA and PMR.
    测试 GCA 和 PMR 中 T2T 策略的成本效益。

Discussion 讨论

These are the first T2T recommendations in GCA and PMR developed by an international multidisciplinary task force complementing current management recommendations in the field. They provide guidance to clinicians on how to implement the T2T approach for GCA and PMR in clinical practice and emphasise the importance of balancing disease burden with unwanted effects of therapy and comorbidities. Furthermore, current gaps in evidence have been identified, and a research agenda has been formulated to provide guidance on how the gaps can be filled by future research.
这些是由国际多学科工作组制定的 GCA 和 PMR 中的第一个 T2T 建议，补充了该领域当前的管理建议。他们为临床医生如何在临床实践中实施 GCA 和 PMR 的 T2T 方法提供指导，并强调平衡疾病负担与治疗和合并症的不良影响的重要性。此外，还确定了当前的证据差距，并制定了研究议程，为如何通过未来的研究填补这些差距提供指导。

With these recommendations, we aim to convey the T2T strategy to the broad medical community given that patients with GCA and PMR are not only treated in highly specialised centres, but also by community-based rheumatologists and other medical disciplines including general practitioners. Observational studies indicate that in GCA and PMR, several principles of T2T such as the selection of treatment according to disease severity/activity, consideration of relevant comorbidities, the maintenance of remission at the lowest possible dose of medication and adequate screening and management of comorbidities are not or insufficiently implemented in current clinical practice.82–84 The present project was independent of, and is thus not officially endorsed by a major rheumatological society, however, this was originally also not the case for the RA or psoriatic arthritis/SpA-T2T activities, which were subsequently embraced by EULAR and other organisations.85–88 The T2T-SLE recommendations were also developed by an international group without initial endorsement by major professional organisations.15 The SLE community with its very heterogeneous views subsequently appreciated the concept of pursuing a treatment target, and the publication of T2T in SLE was essential to stimulate activities in the field to better define treatment targets and management strategies.89 We envision the inclusion of the T2T principle in future management recommendations in GCA and PMR, its implementation in routine clinical practice and ultimately, an improved quality of care resulting in a better long-term quality of life of patients with these diseases.
鉴于 GCA 和 PMR 患者不仅在高度专业化的中心接受治疗，而且还接受社区风湿病学家和其他医学学科（包括全科医生）的治疗，通过这些建议，我们旨在向广大医学界传达 T2T 策略。观察性研究表明，在 GCA 和 PMR 中，T2T 的几个原则，如根据疾病严重程度/活动性选择治疗、考虑相关合并症、以尽可能低的药物剂量维持缓解以及对合并症的充分筛查和管理，是目前的临床实践中没有或未充分实施。 82-84 目前的项目独立于一个主要的风湿病学会，因此并未得到其正式认可，然而，RA 或银屑病关节炎/SpA-T2T 活动最初也并非如此，这些活动随后被 EULAR 和其他组织。 85–88 T2T-SLE 建议也是由一个国际团体制定的，最初并未得到主要专业组织的认可。 15 SLE 界的观点非常不同，随后他们对追求治疗目标的概念表示赞赏，而《SLE 中 T2T》的出版对于刺激该领域的活动以更好地确定治疗目标和管理策略至关重要。 89 我们设想将 T2T 原则纳入 GCA 和 PMR 的未来管理建议中，在常规临床实践中实施，并最终提高护理质量，从而改善患有这些疾病的患者的长期生活质量。

A study formally comparing the management of people with GCA and/or PMR according to a T2T principle with a strategy based on routine clinical care is still warranted. The task force notes that an evidenced-based definition of remission is absent, which is in contrast to the situation in many other rheumatic diseases.13–16 There is an ongoing ACR/EULAR project to develop response criteria in GCA and in addition, OMERACT projects are currently underway to develop definitions of remission in GCA and PMR. Another important uncertainty is the role of imaging. Whether imaging-based absence of inflammation should be a treatment target, which imaging methodology should be used to monitor the disease or whether imaging should be a component of clinical remission are unclear so far. The assessment of disease activity in patients receiving IL-6 receptor inhibitors is another challenge given that these drugs directly suppress ESR and CRP and thus render these acute phase reactants unreliable as measures of disease activity. Evaluation of alternative markers of systemic inflammation is urgently needed, including alternative laboratory tests, such as osteopontin or serum calprotectin, as well as imaging.90 91
仍然有必要开展一项研究，正式比较根据 T2T 原则对 GCA 和/或 PMR 患者的管理与基于常规临床护理的策略。该工作组指出，缺乏基于证据的缓解定义，这与许多其他风湿病的情况形成鲜明对比。 13-16 有一个正在进行的 ACR/EULAR 项目旨在制定 GCA 中的缓解标准，此外，OMERACT 项目目前正在进行中，以制定 GCA 和 PMR 中的缓解定义。另一个重要的不确定性是成像的作用。迄今为止，尚不清楚基于影像学的无炎症是否应成为治疗目标，应使用哪种影像学方法来监测疾病，或者影像学是否应成为临床缓解的一个组成部分。评估接受 IL-6 受体抑制剂的患者的疾病活动性是另一个挑战，因为这些药物直接抑制 ESR 和 CRP，从而使这些急性期反应物作为疾病活动性的衡量标准变得不可靠。迫切需要评估全身炎症的替代标志物，包括替代实验室测试，例如骨桥蛋白或血清钙卫蛋白，以及成像。 90 91

The question of whether telemedicine should play a role in patient management in addition to face-to-face visits remains open. During the COVID-19 pandemic, many people with GCA and PMR were followed by remote consultation rather than face-to-face evaluation, however, the role of this technique is unclear, once the pandemic is over.92 93
除了面对面就诊之外，远程医疗是否应该在患者管理中发挥作用的问题仍然悬而未决。在 COVID-19 大流行期间，许多 GCA 和 PMR 患者接受了远程咨询而不是面对面评估，但是，一旦大流行结束，这种技术的作用尚不清楚。 92 93

The main limitation of our recommendations is the low LoE supporting the individual statements. While a broader search would have identified more papers, the task force was of the opinion that if a study did not have an adequate control arm (which was the most important inclusion criterion in our SLR), the observed effects could not be attributed to the T2T strategy and would thus be uninformative. The research agenda is, therefore, an important product of this project hopefully stimulating further research in the field.
我们建议的主要限制是支持个别陈述的低 LoE。虽然更广泛的搜索会发现更多论文，但工作组认为，如果一项研究没有足够的控制臂（这是我们 SLR 中最重要的纳入标准），则观察到的效果不能归因于T2T 策略因此无法提供信息。因此，研究议程是该项目的重要产品，希望能够刺激该领域的进一步研究。

Despite the limited evidence, we expect these T2T recommendations contribute to high-quality clinical care in GCA and PMR. Unresolved issues and areas of further study are outlined in the research agenda. We anticipate that new developments in the management and assessment of disease states and outcomes will take place in the coming years, which will affect these recommendations and necessitate amending them.
尽管证据有限，我们预计这些 T2T 建议有助于 GCA 和 PMR 的高质量临床护理。研究议程中概述了未解决的问题和进一步研究的领域。我们预计未来几年疾病状态和结果的管理和评估将出现新的发展，这将影响这些建议并需要对其进行修改。

Ethics statements 道德声明

Patient consent for publication
患者同意发表

Acknowledgments 致谢

The authors would like to thank Louise Falzon for her work in the development of the literature search strategy. We also thank Carol Maryman, Raashid Luqmani, Christian Mallen, Sara Monti, Sarah Mackie, John Stone, Ken Warrington, Mehrdad Maz, Rula Hajj-Ali, Robert Spiera, Christian Pagnoux, Elaine Yacyshyn, Catherine Hill, Alex W Hewitt and Eun-Bong Lee for critically revising the manuscript.
作者要感谢 Louise Falzon 在制​​定文献检索策略方面所做的工作。我们还要感谢 Carol Maryman、Raashid Luqmani、Christian Mallen、Sara Monti、Sarah Mackie、John Stone、Ken Warrington、Mehrdad Maz、Rula Hajj-Ali、Robert Spiera、Christian Pagnoux、Elaine Yacyshyn、Catherine Hill、Alex W Hewitt 和 Eun-李奉 (Bong Lee) 对手稿进行了批判性修改。

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