来氟米特治疗老年类风湿性关节炎的疗效评价(英文)

目的:探讨来氟米特治疗类风湿关节炎的疗效和不良反应。方法:选择23例类风湿关节炎患者,用来氟米特20mg/d口服,疗程为12周,比较6周和12周的疗效。结果:治疗6周时病情明显进步3例,进步3例,改善10例,总有效率为70%。12周时明显进步5例,进步9例,改善6例,总有效率为87%。5例发生不良反应(22%),表现为皮疹、白细胞下降、脱发、瘙痒,2例停药(脱落率9%)。无严重不良反应。结论:来氟米特治疗老年类风湿关节炎有效且相对安全。     

An antidestructive effect of leflunomide in early rheumatoid arthritis

AIM: To study effects of leflunomide on inflammatory and destructive processes in patients with early rheumatoid arthritis (RA). MATERIAL AND METHODS: The trial included 33 patients (27 females and 6 males) with a significant diagnosis of RA (A CR criteria) aged 19 to 60 years and duration of the disease from 6 months to 3 years (15.97 +/- 9.70 months). The activity of the inflammatory process and treatment efficacy were assessed by severity of the articular syndrome, duration of morning stiffness (DMS), pain and the disease activity (VAS), device examination, the disease activity by DAS28 indices, etc. The articular syndrome was assessed by the number of painful joints (NPJ), number of swollen joints (NSJ), etc. The functional status of the patient was evaluated by Keitel test, HAQ and hand grip. Calculations were made of erosive arthritis progression rate (EAPR) and joint fissure narrowing progression rate (FNPR). All the patients received leflunomide (100 mg/day for 3 days, then 20 mg/day). A 12-month course was finished by 14 patients, 4 patients were withdrawn because of side effects, the rest--by social causes. RESULTS: To the end of the trial leflunomide reduced NPJ by 84%, NSJ--by 95%, DMS--by 88%, articular pain by VAS--by 66%, the disease activity by VAS--by 70%. A positive trend in DAS28 criterium was observed (a significant suppression of RA activity after 1 month of therapy by 18%, after 4 months--by 39%, after 6 months--by 43%, by the end of the treatment--by 48%). For the initial 6 months EAPR was 0.50 +/- 0.67, for the following 6 months it lowered to 0.37 +/- 1.00, while FNPR decreased to 1.14 +/- 1.26 vs. 1.31 +/- 2 58 for initial 6 months. A positive change of the level of type 3 matrix metalloproteinase (a 20% and 16% by month 4 and to the end of the trial, respectively) was registered. CONCLUSION: A positive effect of leflunomide on RA inflammatory activity and progression rate of joint destruction was confirmed.     

来氟米特和甲氨喋呤联合治疗重症类风湿关节炎短期研究

类风湿关节炎（rheumatoid arthritis,RA）是以慢性进行性关节病变为主的自身免疫性疾病,单一药物治疗不易在较短时间内获得缓解,特别是那些重症患者。O＇Dell等01研究报告了甲氨喋呤（MTX）,羟氯喹（HCQ）．柳氮磺吡啶（SSZ）联合治疗RA较单独用药更好,不良反应不增加。2002年Landewe等报告了慢作用抗风湿药联合治疗RA的5年双盲、对照结果,进一步确定了O’Dell等的经验。来氟米特（LEF）和甲氨喋呤（MTX）联合治疗活动期重症RA的疗效及安全性的报道尚少见。笔者对此进行了有益的探索。     

Changes in indices of inflammatory activity in patients with rheumatoid arthritis during early stages of basic therapy with leflunomide

AIM: To assess leflunomide efficacy and tolerance in patients with rheumatoid arthritis (RA) during the first four months of the treatment. MATERIAL AND METHODS: The study included 200 RA patients treated in four Moscow clinical centers. Leflunomide was given in a dose of 100 mg/day for 3 days, then 20 mg/day for 16 weeks. The activity of the disease according to the criterion DAS 28 was assessed before the treatment and 4, 8, 12 and 16 weeks after the treatment start. RESULTS: RA activity diminished considerably after one month of leflunomide treatment. Later, the articular syndrome continued to improve. A significant improvement by DAS 28 was observed after 16 weeks of the treatment in 65% (129 of 200) patients, high RA activity persisted only in 17 of 90 patients. CONCLUSION: Leflunomide reduces articular inflammation and raises RA patients' quality of life at early stages of the treatment. This reduction continued for 4 months of the study. Therefore, adequate assessment of leflunomide efficacy should be made only after 4-6 months of therapy.     

Cost of rheumatoid arthritis in france: comparison leflunomide/etanercept

Treatment of rheumatoid arthritis was deeply modified with the availability since 1999 of anti-TNFalpha. The clinical superiority of these drugs compared to traditional treatments is proven, but can one make the assumption that the cost of these innovative treatments is partially compensated by a reduction of consumption of other health resources? A retrospective observational study was carried out in the Midi-Pyrenees area, from the point of view of health insurance, to compare the consumed health resources between two cohorts of patients, one treated by etanercept (Enbrel) and the other by leflunomide (Arava). Two hundred and fifty three patients were included in the etanercept cohort and 539 in the leflunomide cohort. The average annual PR cost for a patient treated with etanercept is 13 936 euro and 5 764 euro for a patient treated with leflunomide. The health costs avoided by recourse to etanercept do not compensate the high cost of this drug.     

小剂量来氟米特治疗类风湿关节炎的长期疗效

目的观察小剂量来氟米特治疗类风湿关节炎的长期临床疗效。方法28例类风湿关节炎病例随机进入治疗组（15例）及对照组（13例）。治疗组采用小剂量来氟米特（略去负荷剂量）,日剂量10mg维持,对照组使用柳氮磺胺吡啶治疗,1．5-2.0 g/d。观察期18个月,主要疗效指标为肿胀、压痛关节数、患者及医师对疾病状况总体评价;次要疗效指标为疼痛视觉模拟评分、晨僵时间、健康评价问卷（HAQ）、C反应蛋白;同时记录美国风湿病学会疗效评价指标（ACR20、50）。结果治疗18个月后：主要疗效指标肿胀关节数改善及疾病总体评价,治疗组均优于对照组[肿胀关节数：（-8．5±6．3）、（-7．9±6．4）个,患者主观评价：（-1.4±0．8）、（-1．2±0．6）分,医师主观评价：（-1．4±1．2）、（-1．3±0．9）分,P均〈0．01];在次要疗效指标方面,治疗组疼痛评分、晨僵时间及HAQ评分改善优于对照组[疼痛VAS评分：（-32．4±23．7）、（-31．6±24．8）分,晨僵时间：（-97．84-6．2）、（-92．4±5．2）min,HAQ：（-0．62±0．08）、（-0．57±0．02）分,P均〈0．01]。达到ACR20标准的患者,治疗组占76．9％,对照组为75．0％（P〉0．05）;达到ACR50标准的患者分别占61．5％、47．0％（P〈0．05）。研究过程中治疗组胃肠道反应轻微,2例出现血压升高,2例出现肝酶升高,2例退出;对照组有1例退出。结论长期小剂量来氟米特治疗活动性类风湿关节炎,与柳氮磺胺吡啶相比疗效确切,耐受性好。     

Statin therapy in rheumatoid arthritis

Rheumatoid arthritis, a chronic inflammatory polyarthritis that destroys synovial joints, is associated with systemic as well as local inflammation and with an increased risk of cardiovascular disease and death not fully explained by traditional cardiac risk factors. Statins (HMG-coA reductase inhibitors), medications originally designed to lower cholesterol, have been shown to have powerful effects on decreasing cardiovascular mortality rates in the general and high-risk populations. Not all of this protective benefit appears to be mediated by lowered cholesterol levels. Statins also influence multiple steps in the inflammatory process, including leukocyte migration and adhesion, T-cell stimulation, nitric oxide bioavailability, generation of free radicals, and angiogenesis. Recent studies show that statins may provide mild anti-inflammatory benefit in rheumatoid arthritis, in addition to reducing cardiovascular risk.     

Structum therapy of patients with rheumatoid arthritis

AIM: To study efficacy of the chondroprotector chondroitin sulphate (structum, Pier Fabr Medicament Production, France) in patients with rheumatoid arthritis (RA) and secondary osteoarthrosis of the knee joints. MATERIAL AND METHODS: 15 women with a long history of RA (mean duration 11.9 years) entered an open non-randomized trial of structum. The patients had a severe progressive highly active RA with a definite x-ray stage of the disease. 13 patients had a positive rheumatoid factor (1:80 to 1:1280) and involved knee joints which had been affected for 1 to 10 years (mean 5.3 years). The second x-ray stage was in 8 patients, the third stage of knee joints arthrosis was in 7 ones. A marked pain syndrome in the knee joints upon movement (mean 64.7 mm by VAS) was observed in all the examinees and at rest (mean 28 mm by VAS) in 13 of 15 patients. Structum was given according to a standard scheme: 500 mg 3 times a day for 3 weeks than 500 mg 2 times a day for up to 6 months. Basic drugs for RA were the same for all the observation period. RESULTS: Structum noticeably improved knee joint function (mean Leken's index 12.8, 11.3 and 9.4 scores before the treatment, on treatment month 3 and 6. Movement pain syndrome VAS reduced from 64.7 mm at the start to 51 mm 3 months and 37.5 mm 6 months later, rest VAS--from 19 to 10.3 and 6.4 mm, respectively. The demand in intraarticular glucocorticoids went down from 52 injections at the start of therapy to 6 after 6 months. Side effects for 6 months were absent. Overall efficacy was good (73.3% and 80%) as judged by the doctors and patients, respectively. After 6 months of therapy control x-rays found no progression of destructive changes in the knee joints (by MRI--in 4 patients). CONCLUSION: Structum has a marked positive therapeutic effect in patients with severe and long-term course of RA with associated pronounced secondary joint arthrosis.     

辛伐他汀对类风湿关节炎的治疗作用研究

目的探讨辛伐他汀治疗类风湿关节炎（RA）的免疫学机制，为辛伐他汀治疗活动期类风湿关节炎以及改善其预后提供实验依据。方法70例活动期RA患者随机分为两组，治疗组：辛伐他汀40mg／d＋甲氨蝶呤10mg／周＋来氟米特20mg／d；对照组：甲氨蝶呤10mg／周＋来氟米特20mg／d。分别于治疗前、治疗后12周、24周用放射免疫法测白细胞介素6（IL-6）、肿瘤坏死因子α（TNF-α），酶联免疫法测基质金属蛋白酶3（MMP-3）的浓度，观察辛伐他汀对RA患者炎性因子的影响。结果（1）治疗前两组各项指标差异无统计学意义（P均〉0．05）；（2）RA患者血清中致炎因子IL-6、TNF-α、MMP-3水平与CRP的水平相关；（3）治疗12周时治疗组和对照组相比炎性凶子IL-6、TNF-α、MMP-3及临床指标的下降无统计学意义（P均〉0．05）；（4）治疗24周时治疗组和对照组相比炎性因子IL-6、TNF-α、MMP-3及临床指标的下降有统计学意义（P均〈0．05）；（5）两组的不良反应差异无统计学意义（P均〉0．05）。结论辛伐他汀可以降低RA致炎因子的水平；辛伐他汀不但可以配合免疫调节剂治疗活动期RA，而且对预防和治疗RA引起的早期动脉粥样硬化起着非常重要的作用，从而改善了RA的病情和预后。     

Auranofin therapy in rheumatoid arthritis

Gold is well established as an agent to suppress progressive rheumatoid arthritis. Until recently, gold could only be given parenterally. An orally absorbable gold compound, auranofin, has been undergoing clinical trials in the last 6 years. Auranofin has some effects on the immunologic system, demonstrated in vitro, that differ from its parenteral counterpart, GST. Auranofin appears to have clinical effectiveness in rheumatoid arthritis that approximates that of parenteral gold. Although gastrointestinal toxicity is more frequent with auranofin, renal toxicity is distinctly less frequent than with parenteral gold. There is preliminary evidence that auranofin may have a disease-altering capability, as measured by serial radiographs, similar to that of parenteral gold.     

Progressive heart block in active rheumatoid arthritis

A 68-year-old woman presented with active rheumatoid arthritis (RA) and severe extra-articular manifestations. During the course of her treatment, her electrocardiogram (ECG) transformed from normal sinus rhythm to left bundle branch block and finally to complete heart block (CHB). Investigations ruled out an ischaemic event. A permanent pacemaker was inserted due to the symptoms of heart failure and she made an uneventful recovery. CHB in RA is probably a marker of severity of the disease.     

类风湿关节炎治疗新策略

生物制剂的诞生给类风湿关节炎（rheumatoid arthritis,RA）患者的治疗效果和预后带来了戏剧性的变化,一些新的标志物和影像学检查手段为RA早期诊断提供了帮助。因此,早期诊断、早期治疗、达标控制、个体化治疗已成为RA治疗的新策略。     

类风湿关节炎患者活动期血小板的活化功能

目的：通过观察类风湿关节炎患者外周血血小板活化功能指标CD62P和CD63的表达水平变化，分析其与类风湿关节炎病情活动性的关系。 方法：选择2004—07／2005—12在上海交通大学附属第六人民医院肾脏风湿科门诊及病房就诊的类风湿关节炎患者28例，其中活动期18例，缓解期10例，均自愿参加观察。另外选择15例健康志愿者作为正常对照组。空腹采血2mL至20g／L乙二胺四乙酸抗凝试管，立即行单克隆抗体直接标记，30min内应用流式细胞仪检测外周血血小板CD62P和CD63的表达水平；同时采用免疫比浊法测定C-反应蛋白；应用魏氏法测定血沉。 结果：送检血样均合格，43例观察对象全部进入结果分析。①正常人外周血血小板CD62P，CD63的表达量很低，活动期类风湿关节炎组患者血小板CD62P，CD63的表达量明显升高（P〈0．01），但缓解期类风湿关节炎组与正常对照组接近。②正常对照组C-反应蛋白表达量很低，血沉不快，活动期类风湿关节炎患者C-反应蛋白浓度明显升高，血沉加快（P〈0．01），缓解期类风湿关节炎组与正常对照组接近。③活动期类风湿关节炎组患者外周血血小板CD62P的表达量与C-反应蛋白、血沉呈正相关（r=0．5224，0．7048，P〈0.01）；外周血血小板CD63表达量与血沉呈正相关（r=0．4476，P〈0．05），而CD63表达量与C-反应蛋白无相关性（P〉0.05）。 结论：血小板活化功能对评估类风湿关节炎病情活动性可能有意义。