肿瘤坏死因子拮抗剂治疗风湿性疾病安全性的短期临床观察

目的 描述肿瘤坏死因子(TNF)-α拮抗剂治疗风湿性疾病发生的不良反应,评价临床应用的安全性和耐受性.方法 对2007年1月至2008年10月使用TNF-α拮抗剂的患者从临床症状、体征及实验室检查方面记录使用过程中发生的不良反应及程度和最终结局.结果 78例患者中35%(27/78)为类风湿关节炎(RA),41%(32/78)为强直性脊柱炎(AS),17%(13/78)为银屑病关节炎(PsA),6%(5/78)为未分化脊柱关节病(uSpA).59例患者使用依那西普,7例(12%)发生注射局部反应、上呼吸道感染及结核病等不良反应.19例患者使用英夫利西单抗,3例(16%)发生不良反应,1例(AS)为上呼吸道感染,1例(AS)前两次均在输注完24 h内出现伞身红色丘疹及心悸,1例(RA)输注4次后出现不明原因发热.部分不良反应可自行消失,其余经适当处理后痊愈.结论 证实依那西普和英夫利西单抗治疗风湿性疾病具有较好的安全性和耐受性,发生的不良反应是温和的,经适当处理可痊愈.     

重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白治疗强直性脊柱炎的多中心双盲随机对照临床研究

目的 评价重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白(rhTNFR:Fc)治疗活动性强直性脊柱炎(AS)的临床疗效和安全性.方法 本研究前6周为随机、双盲、安慰剂对照临床试验,后6周为开放研究.143例活动性AS患者随机接受6周的每周2次rhTNFR:Fc(25 mg)或安慰剂皮下注射,主要疗效指标为达到ASAS20的患者比例,次要疗效指标包括达到临床显效的患者比例,与基线值相比Bath AS疾病活动指数、Bath AS功能指数、Bath AS测量指数、脊柱痛、夜间痛、脊柱炎症、患者总体评估指数、肌腱端指数、关节肿胀指数改善的状况.结果 rhTNFR:Fc治疗可使患者获得显著改善,6周时68%患者达到治疗反应,而安慰剂组仅28%(P＜0.001);其他各项疗效指标在治疗组也有明显的改善.rhTNFR:Fc耐受性好,最常见的治疗相关的不良反应为注射部位皮肤反应.结论 rhTNFR:Fc的安全性和耐受性好,能迅速减轻AS的症状和体征,控制AS患者的病情活动.     

肿瘤坏死因子受体-Fc融合蛋白治疗类风湿关节炎与强直性脊柱炎短期疗效及不良反应的差异

目的 观察重组人Ⅱ型肿瘤坏死因子受体-抗体Fc融合蛋白[rhTNFR:Fc,益赛普(etanercept)]治疗类风湿关节炎(RA)及强直性脊柱炎(AS)的疗效及不良反应,评估其在不同关节病中的作用.方法 对18例难治性RA和22例难治性AS患者,使用ATNFR:Fc 25 mg/次,每周2次皮下注射,持续3个月.在治疗前和治疗后2、4、12周进行疗效及不良反应评估.RA组和AS组疗效评价分别采用美国风湿病学会(ACR20)H和ASAS20疗效评价标准.结果 ①rhTNFR:Fc治疗后As组达到ASAS20的总体有效率为95.5%,而RA组达到ACR20为50%,组间比较差异有统计学意义(P＜0.01);②AS组在rhTNFR:Fc治疗第2、4、12周时达到ASAS20疗效的患者分别为12例、21例和21例,而RA组达到ACR20疗效的为3例、5例和9例,各时段组间比较差异有统计学意义(P＜0.01);③RA组发生不良反应的患者占50%,显著高于AS组的9%(P＜0.01).RA组因无效及不良反应停药的患者5例,而AS组仅1例,脱漏率差异有统计学意义(P＜0.05),AS组的依从性好于RA组;④两组治疗前与治疗后12周X线比较均无明显改变.结论 相对RA患者总体反应而言,AS组患者对rhTNFR:Fc治疗起效快,有效率高,不良反应少,依从性好:但两组治疗前后关节X线均无明显改变.     

rhTNFR:Fc对类风湿关节炎患者血清中致炎及抗炎性细胞因子的影响

目的探讨重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白[rhTNFR：Fc，益赛普（etanercept）]治疗类风湿关节炎（RA）的免疫学机制，了解rhTNFR：Fc对RA患者血清中致炎及抗炎性细胞因子的作用，比较rhTNFR：Fc和甲氨蝶呤（MTX）对这些细胞因子作用的不同，为rhTNFR：Fc治疗RA提供进一步的实验依据。方法采用酶联免疫吸附试验（ELISA）检测RA患者rhTNFR：Fc治疗前后血清中白细胞介素（IL）-1、IL-6、IL-1、肿瘤坏死因子（TNF）-α和干扰素ONF）-γ度。观察rhTNFR：Fc对细胞因子的影响。结果①RA患者血清中的炎性细胞因子TNF-α、INF-γ、IL-1β、IL-6的水平均高于健康对照组，其中IL-6、INF-γ、TNF-α的水平与健康对照组相比差异有统计学意义（P〈0．01），抗炎性细胞因子IL-10的水平低于健康对照组，但两者相比差异无统计学意义（P〉0．05）。②rhTNFR：Fc治疗RA后血清中Th1型细胞因子TNF-α、INF-γ、IL-1β、IL-6水平均明显降低（P〈0．01），而Th2型细胞因子IL-10的水平明显提高（P〈0．01）。③RA患者血清中TNF-α水平与肿胀关节数及肿胀关节指数呈正相关（P〈0．05）。④对临床指标的分析表明，rhTNFR：Fc治疗RA疗效确切。结论rhTNFR：Fc可以降低RA患者血清中TNF-α、INF-γ、IL-1β、IL-6的水平，同时升高IL-10水平；在抑制了Th1型细胞因子的同时．增强了Th2型细胞因子的效应．从而改善RA的病情。     

重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白联合改善病情抗风湿药治疗中国人群风湿性疾病的安全性研究

目的 评价注射用重组人Ⅱ型肿瘤坏死因子α受体-抗体融合蛋白(rhTNFR:Fc)治疗大样本量风湿性疾病患者的安全性.方法 观察从2006年5月至2009年3月间使用rhTNFR:Fc治疗的类风湿关节炎(RA)、强直性脊柱炎(AS)、幼年特发性关节炎(JIA)和银屑病关节炎(PsA)患者治疗期间内所发生的不良事件.结果 共对2041病例患者进行观察,其中RA 1388例,AS 421例,其他232例.其中RA中不良事件发生率为13.47％,最常见的为注射部位反应(2.67％)、皮疹(1.87％)和转氨酶升高(1.80％).AS总的不良事件发生率为10.45％,常见的是注射部位反应(5.23％)、转氨酶升高(2.38％)和皮疹(0.71％).全部感染的发生率为2.40％,最常见的感染为上呼吸道感染.本次研究中未观察到严重不良事件、死亡、结核病和恶性肿瘤的发生.结论 rhTNFR:Fc治疗RA、AS等风湿性疾病具有良好的安全性.     

英夫利西单抗与改变病情的抗风湿药物治疗强直性脊柱炎的临床对比研究

目的 对单克隆抗体英夫利西单抗与传统改变病情的抗风湿药物(DMARDs)治疗强直性脊柱炎(AS)的临床疗效进行对比观察,以评价2种药物治疗AS的有效性和安全性.方法 60例确诊的活动期AS患者,随机分为治疗组及对照组,每组30例,治疗组分别于0、2、6、12周给予英夫利西单抗(5mg/kg),对照组给予传统DMARDs(柳氮磺吡啶或来氟米特),随访12周.观察主要疗效指标:治疗终点时达到AS疗效评价标准(ASAS)20的患者比例;次要疗效指标:治疗终点时达到ASAS 50的患者比例,不同时间点与基线值相比Bath AS疾病活动指数(BASDAI)、Bath AS功能指数(BASFI)、脊柱痛、脊柱炎症、患者总体评估指数(PGA)、目视模拟测试表(VAS)及红细胞沉降率(ESR)、C反应蛋白(CRP)变化的情况.计量资料采用t检验,计数资料采用x2检验.结果 2组患者在治疗第12周时与治疗前比较,ASAS 20(93%和47%)、ASAS 50(57%和27%)及BASDAI(2.8±0.4和4.9±1.2)、BASFI(2.8±0.9和4.0±1.1)、脊柱痛(2.5±1.0和3.9±1.2)、脊柱炎症(2.3±1.1和4.4±1.2)、PGA VAS(2.6±1.5和4.8±1.1)及ESR[(9±5)和(26±12)mm/1 h]、CRP[(5±3)和(19±12)mg/L]均改善,差异具有统计学意义(P<0.05).其中英夫利西单抗治疗组改善更为明显,优于传统DMARDs组(P<0.05).2组患者均无严重不良反应发生,最常见的不良反应为上呼吸道感染、胃肠道刺激症状及输液反应,英夫利西单抗组不良反应的发生率明显低于传统DMARDs组.结论 英夫利西单抗与传统DMARDs比较,能迅速减轻AS的症状与体征,并可改善AS患者的功能、活动范围和生活质量,具有良好的安全性和耐受性.     

英夫利西单抗联合硫唑嘌呤治疗中重度克罗恩病的疗效研究

背景:激素和免疫抑制剂是克罗恩病(CD)的传统治疗药物,然而部分CD患者对传统药物耐药或依赖。目的:评价英夫利西单抗联合硫唑嘌呤治疗中重度CD的有效性和安全性。方法:24例CD患者随机分为英夫利西单抗组、硫唑嘌呤组、英夫利西单抗联合硫唑嘌呤组(联合治疗组)。英夫利西单抗组于第0、2、6周给予英夫利西单抗5mg/kg,随后每隔8周给予英夫利西单抗5 mg/kg;硫唑嘌呤组给予硫唑嘌呤2.5 mg/kg qd;联合治疗组给予硫唑嘌呤2.5 mg/kg qd,并于第0、2、6周给予英夫利西单抗5 mg/kg,随后每隔8周给予英夫利西单抗5 mg/kg。治疗第26周末以CD疾病活动指数(CDAI)和内镜检查评价治疗疗效。治疗期间记录患者不良反应发生情况。结果:治疗第26周末,联合治疗组的临床总有效率和内镜下总有效率较英夫利西单抗组和硫唑嘌呤组均显著升高(P<0.05);治疗第26周末联合治疗组血红蛋白水平较治疗前显著升高(P<0.05),ESR和CRP水平治疗前均显著降低(P<0.05);治疗期间联合治疗组无严重不良反应发生。结论:对于激素抵抗或依赖的中重度CD患者,英夫利西单抗联合硫唑嘌呤的疗效优于单用英夫利西单抗或硫唑嘌呤。     

英夫利西单抗对炎症性肠病的疗效及安全性分析

目的 了解英夫利西单抗对炎症性肠病的疗效及安全性.方法 回顾性分析北京军区总医院2007年1月-2013年1月住院的27例激素抵抗或依赖中-重度IBD患者的临床及内镜资料,分别在用药后6周、30周、54周进行Mayo或CDAI评分,总结结肠镜下黏膜改变,并记录不良反应.结果 英夫利西单抗对CD患者有效率为89.5％,激素抵抗或依赖的UC患者有效率为83.0％,二者比较差异无统计学意义(P＞0.05),总体有效率为84.8％,7例达到黏膜愈合.5例患者发生不良反应,包括输液反应、呼吸道感染、白细胞轻度降低.结论 英夫利西单抗对CD及UC患者疗效好,不良反应轻,具有较好的临床应用价值.     

抗肿瘤坏死因子-α治疗对强直性脊柱炎患者外周血CD4+CD25+T细胞调节作用的初步研究

目的 探讨CD4^＋CD25^＋T调节细胞（Treg）在强直性脊柱炎（AS）患者发病机制中的作用，并通过其在抗肿瘤坏死因子（TNF）-α治疗前后的变化，了解抗TNF-α制剂治疗AS的免疫学机制。方法 纳入的10例AS患者均符合1984年修订的纽约标准。治疗使用重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白（rh TNFR—Fc）腹部皮下注射，50mg，每周1次×8周。健康志愿者10名，分别抽取外周血10ml，常规分离淋巴细胞惮核细胞。用流式细胞仪检测CD4^＋CD25^＋T细胞、CD4^＋CD25^high T细胞数量、CTLA-4表达。结果治疗前AS患者外周血中CD4^＋CD25^＋Treg/CD4^＋T为（24＋9）％，高于健康志愿者和经rhTNFR—Fc治疗后的患者（P均〈0．05）。AS患者CD4^＋CD25^high／CD4^＋T淋巴细胞为（6±6）％，亦高于健康志愿者和经rhTNFR—Fc治疗后的AS患者（P均〈0．05）。AS患者CTLA-4为0．15±0．15，高于健康志愿者和治疗后AS患者（P均〈0．05）。结论 在AS患者外周血中CD4^＋CD25^＋Treg数量升高可能参与了AS的发病。CD4^＋CD25^＋Treg数量的变化在一定程度上表现出对于抗TNF-α治疗前后病情的评估作用。     

肿瘤坏死因子-α拮抗剂治疗强直性脊柱炎疗效预测指标的研究进展

强直性脊柱炎(ankylosing spondylitis,AS)是以骶髂关节炎和脊柱慢性炎症为主的全身性疾病,其常见症状为腰背僵硬或疼痛,活动后可以缓解.晚期可发生脊柱强直、畸形以致功能严重受损.肿瘤坏死因子(TNF)-α是一种主要由滑膜巨噬细胞产生的促炎症因子,在AS的发病机制中起到重要作用,目前临床上TNF-α拮抗剂治疗AS的疗效已获充分证据,然而仍有20％～40％的患者疗效不佳.同时高昂的价格和一些不良反应也限制了TNF-α拮抗剂的应用,是否存在敏感因子可以预测TNF-α拮抗剂在AS中的疗效,这对选择患者而言至关重要.本文将近年来有关TNF-α拮抗剂在AS中疗效预测指标的研究综述如下.     

Biologic therapies in the spondyloarthritis: new opportunities,new challenges

Therapeutic options for patients suffering from the more severe forms of spondyloarthritis have been rather limited in the last decades. There is now accumulating evidence that antitumor necrosis factor therapy is highly effective in spondyloarthritis, especially in ankylosing spondylitis and psoriatic arthritis. Based on the data recently published on more than 500 patients with ankylosing spondylitis and psoriatic arthritis, this treatment seems to be even more effective than in rheumatoid arthritis. The antitumor necrosis factor-alpha agents currently available, infliximab (Remicade), etanercept (Enbrel), and adalimumab (Humira), are approved for the treatment of rheumatoid arthritis in the United States and partly in Europe. The situation in spondyloarthritis is different from that of rheumatoid arthritis because there is an unmet medical need, especially in ankylosing spondylitis: no therapies with disease-modifying antirheumatic drugs are available for severely affected patients, especially with spinal disease. Thus, tumor necrosis factor blockers may even be considered a first-line treatment in a patient with active ankylosing spondylitis and psoriatic arthritis whose condition is not sufficiently controlled with nonsteroidal antiinflammatory drugs in the case of axial disease, and sulfasalazine or methotrexate in the case of peripheral arthritis. For infliximab, a dose of 5 mg/kg was required, and intervals between 6 and 12 weeks were necessary to suppress disease activity constantly-also a major aim for long-term treatment. The standard dosage of etanercept is 2 x 25 mg subcutaneously per week. There are no studies yet on adalimumab (standard rheumatoid arthritis dose, 20-40 mg subcutaneously every 1-2 weeks) in spondyloarthritis. Infliximab was very recently approved for AS in Europe. The efficacy of etanercept was first demonstrated in psoriatic arthritis, and it is now approved for this indication. A double-blind study has also been performed in ankylosing spondylitis, with similarly clear efficacy. There is preliminary evidence that both agents do also work in other spondyloarthritis, such as undifferentiated spondyloarthritis. Ideally, both agents will be approved soon for the short-term treatment of severe, uncontrolled spondyloarthritis. In parallel, studies should be performed to document the long-term efficacy of this treatment. There is hope that ankylosis may be preventable, but it remains to be shown whether patients benefit from long-term antitumor necrosis factor therapy and whether radiologic progression and ankylosis can be stopped. Severe adverse events have remained rare. Complicated infections including tuberculosis have been reported. These can be largely prevented by appropriate screening. At it stands now, the benefits of antitumor necrosis factor therapy in ankylosing spondylitis seem to outweigh these shortcomings.     

Effectiveness of infliximab after adalimumab failure in Crohn's disease

AIM: To evaluate the effectiveness of infliximab as a second-line therapy in Crohn’s disease patients after adalimumab failure.METHODS: A historical cohort study in a community-based gastroenterology practice evaluated Crohn’s disease patients treated with infliximab (induction plus maintenance) after adalimumab failure. Patients were identified using a large Spanish database (ENEIDA).RESULTS: We included 15 Crohn’s disease patients who received infliximab after adalimumab failure. Five patients discontinued adalimumab due to loss of response, 3 due to adverse events and 7 due to partial response. After infliximab therapy was started, all patients who had interrupted adalimumab due to loss of efficacy regained response. All patients who discontinued adalimumab due to adverse events responded to infliximab and maintained this response; one of these patients had an uneventful course on infliximab, but 2 developed adverse events. None of the 7 patients who interrupted adalimumab due to partial response reached remission with infliximab.CONCLUSION: Switching from adalimumab to infliximab may be useful in patients who develop adverse effects or loss of response, however, the benefit of infliximab in primary nonresponders was not established.     

Treatment of ankylosing spondylitis with TNF blockers: a meta-analysis

Biological agents directed against tumor necrosis factor (TNF) represent therapeutic options for patients with ankylosing spondylitis with high disease activity despite use of non-steroidal anti-inflammatory drugs. To evaluate the efficacy and safety of the anti-TNF agents infliximab, etanercept, adalimumab, golimumab, and certolizumab for the treatment of ankylosing spondylitis, we performed a systematic review of randomized clinical trials on adult patients with ankylosing spondylitis using articles culled from the EMBASE, MEDLINE, Cochrane Controlled Trials Register and LILACS databases (September/2012), manual literature search, and the gray literature. Study selections and data collection were performed by two independent reviewers, with disagreements solved by a third reviewer. The following outcomes were evaluated: ASAS 20 response, disease activity, physical function, vertebral mobility, adverse events, and withdraws. The meta-analysis was performed using the Review Manager^® 5.1 software by applying the random effects model. Eighteen studies were included in this review. No study of certolizumab was included. Patients treated with anti-TNF agents were more likely to display an ASAS 20 response after 12/14 weeks (RR 2.21; 95 % CI 1.91; 2.56) and 24 weeks (RR 2.68; 95 % CI 2.06; 3.48) compared with controls, which was also true for several other efficacy outcomes. Meta-analysis of safety outcomes and withdraws did not indicate statistically significant differences between treatment and control groups after 12 or 30 weeks. Adalimumab, infliximab, etanercept, and golimumab can effectively reduce the signs and symptoms of the axial component of ankylosing spondylitis. Safety outcomes deserve further study, especially with respect to long-term follow-ups.     

Switching tumour necrosis factor alpha antagonists in patients with ankylosing spondylitis and psoriatic arthritis: an observational study over a 5-year period

OBJECTIVE: To evaluate the clinical response after switching from one tumour necrosis factor (TNF)alpha antagonist to another in patients with ankylosing spondylitis (AS) and psoriatic arthritis (PsA). METHODS: In this ongoing, longitudinal, observational study, data were prospectively collected on efficacy and safety since 2000 for patients starting biological treatments. The present analysis was restricted to patients with a diagnosis of spondyloarthropathy (SpA) who switched from one TNFalpha antagonist to another because of inadequate efficacy or adverse events. RESULTS: In total, 589 anti-TNFalpha-naive patients were registered, of whom 165 had a diagnosis of SpA; 7 patients with AS and 15 with PsA received >1 TNFalpha antagonist. Two patients with PsA were treated with all the drugs. In all, 16 subjects switched from infliximab to etanercept, 7 from etanercept to adalimumab and 1 from etanercept to infliximab. Overall, a clinical response was seen in 75% of patients who changed from infliximab to etanercept, and in 57.1% who switched from etanercept to adalimumab. CONCLUSIONS: The findings of this study on a selected population of patients with SpA indicate that the failure of an initial TNFalpha antagonist does not preclude the response to another one. Further trials are needed to confirm this preliminary observation.     

重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白治疗类风湿关节炎双盲随机多中心对照临床研究

目的研究注射用重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白[rhTNFR：Fc,益赛普,（etanercept）]对活动性类风湿关节炎（RA）患者的疗效及安全性.方法238例患者随机分为试验组和对照组.试验组每周1次口服空白模拟甲氨蝶呤（MTX）,同时接受rhTNFR：Fc皮下注射治疗,每周2次,每次25 mg;对照组每周1次口服定量MTX（每周7.5 mg起,8周内增至15 mg）,同时每周2次皮下注射空白模拟rhTNFR：Fc.疗程24周.疗效评价采用美国风湿病学会（ACR）疗效评定标准.结果治疗2周后,rhTNFR：Fc组ACR20有效率为35.59%,MTX组为22.50%,组间比较差异有统计学意义（P＜0.05）.治疗8周后,rhTNFR：Fc组和MTX组的ACR20、ACR50和ACR70组间比较差异均有统计学意义（（P＜0.05）.治疗12周后,rhTNFR：Fc组ACR20有效率为66.10%,MTX组是51.67%,两组间比较差异有统计学意义（（P＜0.05）.治疗24周后,rhTNFR：Fc组ACR20有效率为75.42%,且ACR70有效率优于MTX组（（P＜0.05）,显示rhTNFR：Fc疗效强于MTX.两组药物之间总的不良反应发生率差异无统计学意义.结论rhTNFR：Fc用于治疗中、重度RA具有良好的安全性和显著的疗效;在前12周治疗期间,rhTNFR：Fc较MTX起效快、效果更明显.     

Therapeutic efficacy and safety of multiple intravenous infusions of infliximab in refractory ankylosing spondylitis patients with axial involvement

OBJECTIVE: To evaluate the clinical response and safety profile of infliximab in refractory ankylosing spondylitis patients. METHODS: Patients with active ankylosing spondylitis, despite methotrexate therapy, were included in an open-label, single-centre study. Patients were given 3-5 mg/kg infliximab infusions at Weeks 0, 2, 6, and q8 etc up to Week 30, together with methotrexate at the dosage taken prior to study inclusion, and were followed-up for a 34-week period. RESULTS: Nine patients with mean age 43 years and mean disease duration 7 years, diagnosed with pure axial ankylosing spondylitis were included. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), duration of morning stiffness, physician's global assessment of disease activity (PhGADA), visual analogue scale (VAS) pain, enthesis index, occiput-to-wall test, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and Bath Ankylosing Spondylitis Functional Index (BASFI) significantly improved by Week 6. No adverse events related with the drug were recorded during the 34-week follow-up period. CONCLUSION: Efficacy results are similar to those previously published. No adverse events were seen during therapy, and antinuclear antibody profiles were negative. The association of methotrexate with infliximab can improve the safety profile.     

单用重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白及联合甲氨蝶呤对胶原诱导性关节炎大鼠关节骨破坏影响的实验研究

目的 通过建立胶原诱导性关节炎(CIA)大鼠模型,评价单用重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白(rhTNFR:Fc)及其联合甲氨蝶呤在抑制CIA大鼠关节骨破坏方面的作用及机制.方法 利用皮下注射牛Ⅱ型胶原诱导Wistar大鼠发病,建立CIA大鼠模型.将造模成功,炎症评分≥2分的CIA大鼠随机分为生理盐水组(0.4 ml/周,腹腔注射)、甲氨蝶呤治疗组(1 mg周,腹腔注射)、rhTN FR:Fc治疗组(0.8 mg,每周2次,腹腔注射)、甲氨蝶呤+rhTN FR:Fc治疗组(甲氨蝶呤1 mg/周+rhTNFR:Fc 0.8mg,每周2次,腹腔注射).治疗8周后,处死大鼠,取踝关节拍摄X线片,胫骨上段行微计算机断层扫描技术扫描和制作硬组织切片,观察各组踝关节骨破坏情况,评价胫骨上段骨小梁变化及骨量变化.统计学处理采用SNK-q检验.结果 治疗8周后,rhTN FR:Fc组,甲氨蝶呤+rhTNFR:Fc组骨小梁面积百分数[(29.1±0.3)％,(26.7±0.6)％]及骨小梁数量(4.4±0.5)/mm,( 4.0±0.6 )/mm]明显高于0.9％氯化钠注射液组和甲氨蝶呤组[(12.9±0.5)％,( 13.2±0.4)％与(2.0±0.3 )/mm,(2.2±0.2)/mm](P＜0.01);rhTNFR:Fc组、甲氨蝶呤+rhTNFR:Fc组骨小梁分离度明显小于0.9％氯化钠注射液组和甲氨蝶呤组(P＜0.01).结论 单用rhTNFR:Fc及联合甲氨蝶呤均具有明显抑制关节骨破坏的作用,且其抑制炎症关节周围骨量减少的作用与抑制局部骨小梁数量减少及骨小梁分离度的增大相关.