来氟米特的合成研究

以乙酰乙酸乙酯为起始原料,经五步反应制得来氟米特,总收率为４３．６％,反应原料易得,反应条件温和,后处理方便,适合工业化生产。     

来氟米特治疗肾炎的临床观察

目的观察来氟米特(Leflunomide)治疗肾小球肾炎的疗效和安全性。方法2002年12月￣2005年12月肾炎住院患者64例,随机分为来氟米特实验组31和常规治疗对照组33例,总疗程6个月。观察治疗前后24小时尿蛋白定量、尿红细胞计数、血清肝肾功能、血象等指标变化,按照疗效评定标准对比分析来氟米特实验组与常规治疗对照组的疗效和安全性。结果①实验组24小时尿蛋白定量、尿红细胞计数较治疗前明显下降,由(3.02±3.1)g降至(0.12±0.16)g,(958±660)个/μl降至(19±5)个/μl,下降幅度明显高于对照组(3.14±3.26)g降至(0.31±0.27)g,(950±680)个/μl降至(25±16)个/μl,P<0.01;②总有效率实验组为100%,对照组为87.1%,两组疗效比较差异有显著性(P<0.01);③副作用发生率实验组12.9%,对照组61.3%。结论来氟米特治疗肾炎较常规治疗起效快、疗程短、疗效好、副作用少,值得临床推广应用。     

雷公藤多苷联合来氟米特治疗类风湿性关节炎疗效观察

目的:观察雷公藤多苷联合来氟米特治疗类风湿关节炎的效果和安全性.方法:60例随机分为对照组和研究组各30例,两组均给予来氟米特治疗,研究组加用雷公藤多苷治疗.比较两组疗效及安全性.结果:临床疗效、实验室指标改善研究组均优于对照组(P＜0.05).结论:雷公藤多苷联合来氟米特治疗类风湿性关节炎能提高疗效,用药安全.     

来氟米特治疗难治性肾病综合征52例临床观察

目的:观察长程应用来氟米特联合泼尼松治疗难治性肾病综合征患者的疗效和安全性.方法:将52例难治性肾病综合征患者随机分为治疗组26例和对照组26例,治疗组采用中等量激素联合来氟米特治疗,对照组采用中等量激素联合环磷酰胺(CTX)冲击治疗,观察两组临床指标变化和不良反应,随访时间12个月.结果:治疗组治疗后24 h尿蛋白定量显著减少P<0.05),血清白蛋白显著升高(P<0.05),完全缓解率46.15%,总有效率80.76%.与对照组比完全缓解率差异有显著性(P<0.05),治疗组12周内显效率高于对照组(P<0.05),不良反应轻微,所有患者耐受性良好.结论:来氟米特能够有效缓解难治性肾病综合征.     

来氟米特用于抢救性治疗减免免疫抑制剂无效的肾移植术后BK病毒性肾病的体会:附4例报告

目的  探讨抢救性应用来氟米特治疗减免免疫抑制剂无效的肾移植术后BK病毒性肾病(BKVN)的临床体会。方法  4例肾移植术后BKVN受者,于术后第135~737日确诊,病理分期A1期2例、B1期1例、B2期1例。均在减免免疫抑制剂治疗0.5~3.0个月无效后,采用来氟米特抢救性治疗,先予50 mg/d连用3 d,达到有效治疗血药浓度后应用20 mg/d维持,观察其疗效及安全性。结果  经过平均6个月(5~7个月)的随访,有效控制BKVN进展者3例,无效者1例(B2期)。服药过程中未发生明显不良反应。结论  肾移植术后BKVN,在减免免疫抑制剂无效时,抢救性应用来氟米特有可能减缓BKVN进展,减少移植肾丢失的发生率。及早发现和诊断BKVN,力求病理学分期较早的情况下及时采取有效治疗措施效果较佳。     

Proposals for leflunomide use to avoid lung injury in patients with rheumatoid arthritis

Abstract

Among the 5,043 consecutive patients registered in the postmarketing surveillance for leflunomide, 61 were reported to have lung injury and 24 died from it. The adjusted multivariate logistic regression analysis of the risk factors showed that preexisting interstitial lung disease posed the greatest risk, as well as loading dose, smoking history, and low body weight of 40 kg or less with odds ratios of 8.17, 3.97, 3.12, and 2.91, respectively. In 12 patients, lung injury developed even 2 months after leflunomide withdrawal. When patients with (n = 9) and without (n = 13) fatal outcome were compared, eight out of the former, and six out of the latter had preexisting interstitial lung disease; the former showed severe hypoxemia, high serum C-reactive protein level, hypoalbuminemia, and continuous lymphocytopenia, and required mechanical ventilation. On the basis of these results and literature review, the committee proposes that leflunomide should only be recommended as a second-line drug, should not be administered to patients with preexisting interstitial lung disease, should also not be administered to patients with smoking history or those with low body weight, and should be administered without loading dose. Careful monitoring is necessary, and when lung injury develops, leflunomide elimination using colestyramine is mandatory.     

Non-biologic remission maintenance therapy in adult patients with ANCA-associated vasculitis: A systematic review and network meta-analysis

ObjectiveTo determine the comparative efficacy of non-biologic treatments for remission maintenance in ANCA-associated vasculitis.MethodsWe identified all randomized trials comparing leflunomide, azathioprine, methotrexate or mycophenolate mofetil in adult patients with granulomatosis with polyangiitis or microscopic polyangiitis. Relapse-free survival was compared through hazard ratios (HR) using a Bayesian fixed-effects network meta-analysis. Multiple sensitivity analyses were performed to explore biases identified in one trial using original trial data.ResultsThree trials were available (leflunomide-methotrexate, methotrexate- azathioprine, azathioprine-mycophenolate). Mycophenolate was inferior to all treatments, although the 95% credible interval (CrI) of the HR relative to methotrexate crossed 1. Leflunomide was superior to azathioprine (HR 0.43 [95% CrI: 0.14–1.3]) and methotrexate (HR 0.47 [95% CrI: 0.18–1.2]), although the 95% CrI also crossed 1. There was a 90% probability that leflunomide was the best treatment. After down weighting the effect of leflunomide vs. methotrexate for early trial termination and slow MTX dose escalation, there remained a 55% probability leflunomide was best.ConclusionBased on indirect evidence, leflunomide is effective in maintaining remission in granulomatosis with polyangiitis or microscopic polyangiitis relative to other non-biologic treatments. Further randomized trials of leflunomide are needed for confirmation.     

Debilitating diarrhoea and weight loss due to colitis in two RA patients treated with leflunomide

Diarrhoea and weight loss are frequently reported adverse events in rheumatoid arthritis (RA) patients receiving the disease-modifying antirheumatic drug (DMARD) leflunomide. According to the available literature these side effects occur mostly during the first 6 months of treatment, are rather mild and rarely lead to treatment withdrawal. In this report, we describe the clinical, endoscopic and histologic findings in two RA patients with severe diarrhoea and important weight loss more than 12 months after starting treatment with leflunomide. In both cases the symptoms were caused by colitis, but one had ulcerative and the other microscopic colitis. Despite treatment with budesonide the complaints only improved after withdrawal of leflunomide, making a causal relationship between this drug and the pathogenesis of colitis probable. The heterogeneous histopathological findings in these two patients, however, do not allow us to draw any definitive conclusions about the mechanism by which leflunomide causes diarrhoea and weight loss in RA patients. We conclude that persistent diarrhoea or weight loss in patients taking leflunomide can be more serious than what is previously reported in the literature. In such cases leflunomide treatment should be stopped and an endoscopic examination of the colon is recommended. Given the long half-life of this drug a washout procedure with cholestyramine should be considered whenever the problem is severe or persistent.     

改良温和悬灸疗法治疗类风湿关节炎70例疗效观察

目的 观察改良温和悬灸疗法在类风湿关节炎中的应用效果.方法 将150例类风湿关节炎患者根据治疗方法的不同分为观察组70例和对照组80例,观察组给予改良温和悬灸疗法,对照组给予常规的西药氟米特片治疗.记录并比较两组患者的临床疗效、各项临床指标以及生活质量的评分.结果 观察组的治疗总有效率为91.43%,明显高于对照组的77.5%,差异具有统计学意义(P<0.05);治疗后,观察组的压痛关节数、肿胀关节数、血小板(PLT)、血沉(ESR)以及类风湿关节炎疾病活动性评分(DAS28评分)均明显优于对照组,差异均具有统计学意义(P<0.05);治疗后及随访的第4个月,观察组生活质量的评分显著高于对照组[(70.5±15.2)分vs (64.3±14.4)分;(81.6±15.5)分vs (71.6±14.3)分],差异具有统计学意义(P<0.05).结论 改良温和悬灸疗法治疗类风湿关节炎的效果明显,且操作方法简单,为治疗类风湿关节炎的较好选择,值得在临床上推广应用.     

百令胶囊联合来氟米特治疗慢性肾小球肾炎的临床研究

目的研究百令胶囊联合来氟米特片治疗慢性肾小球肾炎的临床疗效。方法选取2013年12月—2017年12月河南科技大学第一附属医院接收的100例慢性肾小球肾炎患者作为研究对象,将患者随机分为对照组和治疗组,每组各50例。对照组患者口服来氟米特片,2片/次,1次/d。治疗组患者在对照组基础上口服百令胶囊,4粒/次,3次/d。两组患者均持续治疗12周。观察两组患者的临床疗效,同时比较两组治疗前后的肾功能指标和尿液检查指标水平。结果治疗后,对照组和治疗组的总有效率分别为84.00%、96.00%,两组比较差异具有统计学意义(P0.05)。治疗后,两组患者尿素氮(BUN)和血肌酐(Scr)水平均显著降低,同组治疗前后比较差异具有统计学意义(P0.05);治疗后,治疗组肾功能指标水平显著低于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组患者24h尿蛋白定量(24 hUpro)、尿β2-微球蛋白(β2-MG)和尿红细胞计数(RBC)水平均显著降低,同组治疗前后比较差异具有统计学意义(P0.05);治疗后,治疗组尿液检查指标水平显著低于对照组,两组比较差异具有统计学意义(P0.05)。结论百令胶囊联合来氟米特片治疗慢性肾小球肾炎具有较好的临床疗效,能显著改善患者肾功能和尿液检查指标,安全性较高,具有一定的临床推广应用价值。