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中国系统性红斑狼疮诊疗指南十年首更新,重新定义疾病治疗理念及策略

2020-03-25 MedSci MedSci

中国系统性红斑狼疮研究协作组(CSTAR)正式颁布《2020中国系统性红斑狼疮诊疗指南》(以下简称2020新版《指南》),就中国一线风湿免疫科医师关注的12个临床问题提出推荐意见.

近日,中华医学会风湿病学会、国家皮肤与免疫疾病临床医学研究中心、中国系统性红斑狼疮研究协作组(CSTAR)正式颁布《2020中国系统性红斑狼疮诊疗指南》(以下简称2020新版《指南》),就中国一线风湿免疫科医师关注的12个临床问题提出推荐意见,旨在提高系统性红斑狼疮诊疗的科学性,提高以患者为中心的医疗服务质量。
 
此次更新是继2010年中华医学会颁布《系统性红斑狼疮诊断及治疗指南》后,十年来首次更新。2020新版《指南》以临床问题为导向,以循证科学为依据,接轨国际理念,结合我国国情,在诊断、病情评估及治疗等方面提供规范诊疗建议。
 
SLE患者生存率仍不乐观 “下一个十年” 成最大挑战

系统性红斑狼疮(Systematic Lupus Erythematosus,以下简称SLE )是一种系统性自身免疫病,影响全身多系统和脏器。以反复复发与缓解为主要临床特点,疾病发生早期即可造成广泛器官损害,严重影响患者生存质量;如不及时治疗,会造成受累脏器的不可逆损害,最终导致患者死亡。
 
目前,中国SLE患病人群超过100万,患病率高居世界第二。随着诊治水平不断提高,中国SLE患者的生存率得到显著改善。患病后的10年生存率从1950年代的50%提升至目前的89%。然而,患者的 “下一个十年” 生存状况却不甚乐观,令人担忧。
 
“过去三十年间,SLE患者的预后虽有显著改善,但10年以上的生存率出现明显拐点,25年至30年的生存率从89%骤降至30%。”北京协和医院风湿免疫科主任曾小峰教授介绍,“如何解决患者“下一个十年”的生存问题,预防和减少复发,提升患者生活质量,延缓疾病进展,改善患者长期预后,仍是我国风湿免疫科医生面临的巨大挑战。”
 
新版指南:推进SLE早期诊断,达标治疗,改善长期预后

近十年来,随着新的诊治研究结果与新型治疗药物不断出现,指南制定的理念、方法和技术也在不断发展和更新,2020新版《指南》与时俱进,强调推进SLE的早期诊断与达标治疗。提出SLE治疗应遵循早期、个体化治疗,最大程度延缓疾病进展,降低器官损害,改善预后的原则。并清晰定义了短期和长期治疗目标。
 
“SLE的早期诊断为早期干预、快速达标提供了更多机会和窗口。治疗的短期目标以控制疾病活动、改善临床症状为主,目的是达到临床缓解或可能达到的疾病最低活动度,尽可能的在早期减少器官损害。”曾小峰教授强调:“治疗长期目标的核心在于预防和减少复发。通过药物方案的调整,减少激素等药物不良反应,预防和控制器官损害,降低病死率,提高患者生活质量。”
 
新版指南:合理使用激素,最小化激素相关不良反应
 
新版《指南》将SLE缓解或低疾病活动度评估与治疗策略逐步细分,着力推进达标治疗。特别针对糖皮质激素强调了剂量个体化及病情稳定时尽早减量乃至停药。曾小峰教授强调:“没有激素最终成功减量至相对安全的剂量范围(≤7.5 mg/d),就谈不上实现真正的SLE缓解/低疾病活动,亦就谈不上SLE的达标治疗。” 
 
长期使用激素的不良反应如继发感染、脆性骨折等,会随激素剂量的增加而增多,有研究显示,接受>7.5mg/d泼尼松的SLE患者更易发生激素相关心血管(包括心肌梗死、心力衰竭和脑血管疾病)、肾脏、肌肉骨骼等损害。因此临床医师应尽可能采用控制病情所需的最低激素剂量。 
 
新版指南:增加生物制剂治疗推荐
 
目前,包括糖皮质激素,免疫抑制剂在内的传统治疗方案仍然面临着疾病控制不佳和药物毒性挑战:60%的患者疾病持续活动或反复复发,造成器官不可逆损害和感染等不良预后。数据显示,超过50%的SLE患者死于疾病反复复发,器官受损产生的感染。
 
在药物选择上, 2020新版《指南》首次推荐了包括贝利尤单抗等生物制剂的使用,提出 “经激素和/或免疫抑制剂治疗效果不佳、不耐受或复发的SLE 患者,使用生物制剂能较为显著地提高患者的完全和部分缓解率,降低疾病活动度、疾病复发率及减少激素用量。,,,”
 
新版指南:强调预防和控制感染的重要性


2020新版《指南》同时指出,不恰当使用激素和免疫抑制剂、SLEDAI 评分高、受累器官数量多以及患者发病年龄轻等,是SLE 患者合并感染的主要危险因素 ,强调在SLE 整个治疗期间,应及时评估可能的感染风险。
 
研究显示,我国SLE患者出现狼疮肾炎的比例高达40-60%,另有神经精神狼疮、肺动脉高压等脏器受累表现,病情较其他地区的SLE患者更为严重。新版《指南》针对SLE患者出现器官和系统受累时,也给出了具体的处理意见。
 
曾小峰教授表示:“《2020中国系统性红斑狼疮诊疗指南》的发布具有里程碑式意义,为中国广大风湿免疫科同仁提供了具有循证依据的SLE规范诊治建议,将整体提高中国红斑狼疮诊疗和管理水平,推进早期诊断,达标治疗,最终改善SLE患者的长期预后,提高患者的生存率和生活质量。”
 
参考文献:
 
1,Tektonidou MG, Lewandowski LB, Hu J, et al. Survival in adults and children with systemic lupus erythematosus: a systematic review and Bayesian meta‑analysis of studies from 1950 to 2016[J]. Ann Rheum Dis, 2017, 76(12): 2009‑2016. DOI: 10.1136/annrheumdis‑2017‑211663.
 
2,Fava A, Petri M. Systemic lupus erythematosus: diagnosis and clinical management[J]. J Autoimmun, 2019, 96: 1‐13. DOI:10.1016/j.jaut.2018.11.001.
 
3,Nossent J, Kiss E, Rozman B, et al. Disease activity and damage accrual during the early disease course in a multinational inception cohort of patients with systemic lupus erythematosus[J]. Lupus, 2010, 19(8): 949‐956. DOI: 10.1177/0961203310366572.
 
4,Fei Y, Shi X, Gan F, et al. Death causes and pathogens analysis of systemic lupus erythematosus during the past 26 years[J]. Clin Rheumatol, 2013, 33(1):57‐63. DOI: 10.1007/s10067‐013‐2383‐3.
 
5,Peterknecht E, Keasey MP, Beresford MW. The effectiveness and safety of biological therapeutics in juvenile‐onset systemic lupus erythematosus (JSLE): a systematic review[J]. Lupus, 2018, 27(13):2135‐2145. DOI: 10.1177/0961203318804879.
 
6,Wei L, Liang Y, Zhao Y, et al. Efficacy and safety of belimumab plus standard therapy in patients with systemic lupus erythematosus: a meta‐analysis[J]. Clin Ther, 2016, 38(5):1134‐1140. DOI: 10.1016/j.clinthera.2016.02.022.
 
7,Lee YH, Song GG. Comparative efficacy and safety of intravenous or subcutaneous belimumab in combination with standard therapy in patients with active systemic lupus erythematosus: a Bayesian network meta‐analysis of randomized controlled trials[J]. Lupus, 2018, 27(1):112‐119. DOI: 10.1177/0961203317713143.
 
8,Alshaiki F, Obaid E, Almuallim A, et al. Outcomes of rituximab therapy in refractory lupus: A meta‐analysis[J]. Eur J Rheumatol, 2018, 5(2):118‐126. DOI: 10.5152/eurjrheum. 2018.17096.
 
9,Singh JA, Hossain A, Kotb A, et al. Risk of serious infections with immunosuppressive drugs and glucocorticoids for lupus nephritis: a systematic review and network meta‐analysis[J]. BMC Med, 2016, 14(1):137. DOI: 10.1186/s12916‐016‐0673‐8.
 
10,孙欣, 徐莉莉, 邓艳红, 等. 系统性红斑狼疮并发感染危险因素的Meta 分析[J]. 中华护理杂志, 2015, 50(7):828‐835. DOI: 10.3761/j.issn.0254‐1769.2015.07.013.
 
11,刘志红等.中国狼疮肾炎诊断和治疗指南.《中华医学杂志》.2019年11月26日第99卷.

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  5. [GetPortalCommentsPageByObjectIdResponse(id=1949321, encodeId=778a194932102, content=<a href='/topic/show?id=5ed95833172' target=_blank style='color:#2F92EE;'>#新定义#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=100, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=58331, encryptionId=5ed95833172, topicName=新定义)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6ab940, createdName=hukaixun, createdTime=Wed May 20 11:44:50 CST 2020, time=2020-05-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2017212, encodeId=2408201e212e0, content=<a href='/topic/show?id=9760e69058c' target=_blank style='color:#2F92EE;'>#系统性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76905, encryptionId=9760e69058c, topicName=系统性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2b9b368, createdName=qingrejiedu, createdTime=Fri Feb 12 21:44:50 CST 2021, time=2021-02-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1982794, encodeId=b8e81982e944b, content=<a href='/topic/show?id=89c4e06902e' target=_blank style='color:#2F92EE;'>#疾病治疗#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=74, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=70690, encryptionId=89c4e06902e, topicName=疾病治疗)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d64f419, createdName=qindq, createdTime=Sun Dec 20 11:44:50 CST 2020, time=2020-12-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1387394, encodeId=50ef138e3948f, content=<a href='/topic/show?id=8a3a6814425' target=_blank style='color:#2F92EE;'>#狼疮#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=61, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=68144, encryptionId=8a3a6814425, topicName=狼疮)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7a6e2500005, createdName=sunrural_42825357, createdTime=Fri Mar 27 04:44:50 CST 2020, time=2020-03-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1436251, encodeId=d19014362511b, content=<a href='/topic/show?id=22f8e71238d' target=_blank style='color:#2F92EE;'>#红斑#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=70, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77123, encryptionId=22f8e71238d, topicName=红斑)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=zhouqu_8, createdTime=Fri Mar 27 04:44:50 CST 2020, time=2020-03-27, status=1, ipAttribution=)]
    2020-03-27 zhouqu_8
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