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闵伟琪 三甲
闵伟琪 主任医师
菏泽市立医院 风湿免疫科

EULAR2009RA治疗指南解析

EULAR 2009 RA治疗指南解析

EULAR2009年会上公布了EULAR首个RA治疗指南。该指南有下述特色和优点:①提出RA治疗策略为目标治疗;② 参考真实临床实践经验,追求个体化治疗;③ 充分考虑科学性和经济性的关系;④提出了糖皮质激素治疗地位;⑤ 涉及减药和停药问题。

 

推荐1菏泽市立医院风湿免疫科闵伟琪

早期治疗,即一经诊断RA即开始DMARD治疗。Recommendation 1(treatment start):  Therapy with synthetic DMARDSs should be started as soon as the diagnosis of RA is made.
推荐2

RA治疗的策略是目标治疗。目标是降低疾病活动度、达到临床缓解。实现目标治疗的手段包括:①早期强化治疗;② 严格控制,即密切随访、根据病情活动度调整治疗方案、直至临床缓解;③ 精确的疾病活动评价体系;④ 个体化治疗。Recommendation 2(treat-to-target): Treatment should be aimed at reaching a target of remission or low disease activity as soon  as possible in every patient; as log as the target has not been reached ,adjustment of the treatment should be done by frequent” and strict monitoring
说明:所谓“达标控制”是以降低RA疾病活动度达到临床缓解为目标的更加个性化的治疗策略。它强调早期强化治疗、严格控制(tight control,包括1-3个月1次的密切随访,根据病情活动度调整治疗方案,直到临床缓解)、精确的疾病活动评价体系和个体化治疗。
治疗目标是临床缓解或低度活动,主要是DAS28<2.6-3.2。例如,某患者诊断为RA,早期用MTX 7.5-25mg/w加激素或联合羟氯喹/柳氮磺吡啶,每1-3个月随访1次,判断是否达标(每次随访改善20%以上,6-12个月内达到DAS44<1.6,DAS<2.4,CDAI<2.8等),如果达到了,则继续治疗,维持缓解6个月以上,并可逐渐减药;如果不能达标,则调整方案,使用DMARD加肿瘤坏死因子抑制剂或IL-6拮抗剂,也可使用另一种DMARD加激素。

推荐3 

对活动期RA患者治疗应首选甲氨蝶呤(MTX)。MTX在RA治疗中的地位不可替代,小剂量(7.5~20 mg/w)每周使用是长期最有效和安全的药物,细胞毒和其他副作用主要出现在大剂量(20~30 mg/w)使用时,应个体化选择。 Recommendation 3(first DMARD):  MTX should be part of the first treatment strategy in patient with active RA.说明:MTX是治疗RA的核心药物,小剂量(7.5-20mg/w)是长期最有效和安全的药物,大剂量(20-30mg/w)有细胞毒等其他副作用,根据个体差异决定是否使用大剂量,甚至初始治疗可单用MTX,应快速加量(5mg/w),而慢速减量(2.5mg/w),推荐合并用叶酸可明显减少胃肠道副作用。
推荐4 

在MTX禁忌或不耐受时,替代药物应首选柳氮磺胺吡啶(SSZ)、来氟米特或注射金等。Recommendation 4(alternative first DMARDs):  In case of MTX contraindications(or intolerance), the following DMARDs should be considered as part of the (first) treatment strategy: sulfasalazine,leflunomide and injectable gold。在我国还有一种独特的选择,即雷公藤多甙。
推荐5 

对未使用DMARD的患者,首先应予传统 DMARD单药而非几种DMARD联合治疗。Recommendation 5(Mona vs combi): In DMARD-naïve patients, synthetic DMARD monotherapy rather than combination therapy with other synthetic DMARDs may be applied.
推荐6 

在初始治疗中,糖皮质激素可短期与DMARD联合用于诱导缓解,但应避免10 mg/d以上剂量长期使用。  Recommendation 6(glucocorticoids): Glucocorticoids can be useful as initial short term therapy in combination with synthetic DMARDs说明:大剂量激素(40-60mg/d)可作为诱导缓解,避免长期用超过10mg/d以上的激素,小剂量(<5mg/d)长期维持有争议,需预防骨疏松,不引起高血压糖尿病等。
推荐7

如果用一线DMARD策略治疗目标未达到,且存在预后不良的因素(RF/CC P抗体阳性;早期骨侵蚀;病情快速进展;病情高度活动),则加生物制剂。Recommendation 7(Biologicals 1): If the treatment target is nor achieved with the first DMARD strategy ,addition of a biological DMARD should be considered in case of presence of individual poor prognostic factors(RF/CC P, early erosive disease, rapidly progressive disease, high disease activity). In the absence of poor prognostic factors a switch another synthetic DMARD strategy should be considered

推荐8

对MTX和(或)其他DMARD反应不好,应开始用生物制剂。目前主张开始以TNF抑制剂,并联合使用MTX。Recommendation 8( Biologicals 2):  In patients responding insufficiently to MTX and/or other synthetic DMARDs should be commenced. Current practice would be to start a TNF inhibitor which should be combined with MTX.
推荐9 

对TNF-α抑制剂治疗失败者,应换另一种TNF-α抑制剂、阿巴西普、利妥昔、tocilizumab。Recommendation 9(After a TNF failure): Patients with RA who have failed a first TNF inhibitor therapy, should receive another TNF inhibitor, abatacept, rituximab or tocilizumab
推荐10

 严重难治RA患者或对生物制剂及前述传统DMARD有禁忌者,可联合或单用下述药物:硫唑嘌呤、环孢素、环磷酰胺。 Recommendation 10(Refractory RA): In case of refractory severe RA or contraindications to biological agents or the previously mentioned synthetic DMARDs, the following synthetic DMARDs might be also considered, as monotherapy or in combination with some of the above :azathioprine,cyclosporine A, cyclophosphamide
推荐11 

对每例患者都应考虑强化治疗方案,虽然有预后不良因素的患者获益更大。大量的研究包括CAMERA研究、BeSt研究、TICORA研究、FIN-RACo研究等项研究均证实,强化治疗优于传统治疗。Intensive medication strategies should be considered in every patient,although patients with bad prognostic factors have more to gain.  
推荐12

对病情持续稳定的患者可考虑减药,首先减少或停用糖皮质激素,其次是生物制剂,尤其是如果该治疗联合了DMARD。最后考虑是否减停MTX或其他传统DMARD。Recommendation 12 (Tapering 1):If a patient is in persistent remission, glucocorticoids should be tapered and one can consider tapering biological DMARDs, especially if this treatment is combined with a synthetic DMARD.
推荐13

对于持续长期缓解的患者,可考虑逐渐谨慎地降低DMARD剂量,由医生和患者间共同决定。 Recommendation 13 (Tapering 2): In case of sustained long-term remission, cautious titration of synthetic DMARD dose could be considered , as a share decision between patient and physician.

推荐14 

对未使用过DMARD、有预后不良因素的患者,可考虑MTX联合一种生物制剂。Recommendation 14(Poor-prognosis patients): DMARD-naïve patients with poor prognostic markers might be considered for combination therapy of methotrexate plus a biological.

推荐15 

在调整治疗时,除疾病活动度之外,也应考虑其他因素如骨结构破坏进展、并发症等。Recommendation 15(Other factors): When adjusting therapy , factors apart from disease activity, such as progression of structural damage, co-morbidities and safety issues should be taken into account.

 

闵伟琪
闵伟琪 主任医师
菏泽市立医院 风湿免疫科
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