小剂量来氟米特治疗类风湿关节炎的临床研究

目的：前瞻性观察小剂量来氟米特治疗类风湿关节炎（RA）的临床疗效。方法：32例类风湿关节炎病例随机进入治疗组及对照组。治疗方案治疗组采用小剂量来氟米特（略去负荷剂量,每日剂量10mg维持）,对照组使用柳氮磺胺吡啶治疗,1.5-2.0g/日。观察期6个月,观察指标为主要疗效指标：肿胀、压痛关节数、患者及医师对疾病状况总体评价;次要疗效指标疼痛视觉模拟评分、晨僵时间、美国风湿病学会疗效评价指标（ACR20、50）、健康评价问卷（HAQ）、C反应蛋白。结果：治疗6个月后,主要疗效指标压痛、肿胀关节数改善及医师总体评价,来氟米特均优于柳氮磺胺吡啶（p〈0.05）。在次要疗效指标方面,来氟米特组HAQ评分及C反应蛋白改善优于柳氮磺胺吡啶组（p〈0.05）,两组在关节晨僵改善无明显差异。达到ACR20标准的病例,来氟米特组占56.3%,柳氮磺胺吡啶组占57.1%（p〉0.05）;达到ACR50标准分别为37.5%、35.7%（p〉0.05）。研究中,来氟米特组胃肠道反应轻微,有2例出现血压升高。结论：小剂量来氟米特治疗类风湿关节炎治疗活动性类风湿关节炎,与柳氮磺胺吡啶疗效相当,耐受性好。     

依那西普联合甲氨蝶呤治疗类风湿关节炎疗效分析

目的:探讨依那西普联合甲氨蝶呤治疗类风湿关节炎的疗效。方法:选取2011年至2013年风湿免疫科的60例类风湿关节炎患者,分为对照组和治疗组,其中对照组15例,治疗组45例,两组患者都应用甲氨蝶呤治疗,治疗组患者联合使用依那西普治疗,总疗程12周。比较两组患者治疗前后的临床及实验室指标。采用美国风湿病学会的核心标准作为疗效评定标准。结果:治疗组患者肿瘤坏死因子(tumor necrosis factor,TNF)和白细胞介素(interleukin,IL-1)下降明显,与对照组患者相比差异均有统计学意义(P0.05);治疗后两组患者超敏C反应蛋白(hs-CRP)均较治疗前明显降低,差异均有统计学意义(P0.05);治疗组患者关节疼痛、关节肿胀和晨僵情况较对照组均有显著的改善(P0.05);治疗组患者的休息痛、患者评分以及HAQ评分均显著优于对照组(P0.05);治疗组患者ACR20和ACR70缓解的比例均高于对照组,且治疗组患者达ACR50缓解的比例显著高于对照组(P0.05)。结论:依那西普联合甲氨蝶呤治疗类风湿关节炎的疗效优于单纯的甲氨蝶呤治疗。     

依那西普联合来氟米特治疗强直性脊柱炎的疗效观察及安全性分析

目的:探究依那西普联合来氟米特治疗强直性脊柱炎(AS)的疗效及安全性。方法:收集2015年1月-2016年6月间我院收治的AS患者90例,按随机数字表法分为观察组和对照组,每组各45例。观察组采用依那西普联合来氟米特治疗,对照组则单纯采用来氟米特治疗。记录两组治疗前后的晨僵时间、AS活动性指数(BASDAI)和AS测量指数(BASMI),比较两组治疗总有效率及不良反应发生情况。结果:治疗后,两组患者晨僵时间、BASDAI及BASMI较治疗前均有所下降,且观察组上述各指标均显著低于对照组,差异有统计学意义(P0.05);观察组总有效率显著高于对照组,差异有统计学意义(P0.05);治疗过程中,患者发生的主要不良反应为肝功能损伤、腹泻和过敏性皮疹,但两组不良反应发生率差异无统计学意义(P0.05)。结论:依那西普联合来氟米特可获得比较理想的疗效,且不良反应发生率较低,值得在临床上推广使用。     

针刺加艾灸结合疗法对类风湿性关节炎的近远期疗效

目的:探讨针刺加艾灸配合治疗类风湿关节炎的近远期疗效。方法:选择我院2013年4月~2014年1月门诊病房治疗的74例类风湿关节炎患者为研究对象,以随机数字表法分组,观察组37例,对照组37例,对照组实施西医疗法治疗,观察组在对照组基础上采取针刺配合艾灸治疗,对两组患者治疗后效果进行分析。结果:观察组治疗后1个月有效率为89.19%,对照组为70.27%,差异显著(P0.05);治疗后1年疗效显示,对照组有效率为59.46%,观察组94.59%,两组差异存在统计学意义(P0.05);治疗前两组患者晨僵时间、关节压痛指数、关节肿胀指数、关节功能评分、握力等指标水平无明显差异,治疗后两组患者均有变化,观察组治疗后以上指标水平明显优于对照组,两组差异有统计学意义(P0.05);治疗前血沉(ESR)、C-反应蛋白(CRP)与类风湿因子(RF)指标无明显差异,治疗后均有改善,但是观察组治疗后各项指标水平明显低于对照组,差异有统计学意义(P0.05);对照组治疗后不良反应发生率为16.22%,观察组为2.70%,两组差异有统计学意义(P0.05)。结论:艾灸配合针刺治疗类风湿关节炎可取得较好近远期疗效,提高了患者关节功能及握力,有效缓解晨僵、关节疼痛、肿胀等症状。     

类风湿关节炎药物治疗的规范化及临床实践探析

目的：在前人研究基础上进一步调查和研究类风湿关节炎（RA）患者药物治疗的规范化状况。方法：对湘潭市中心医院2012年3月至12月门诊就诊的120例风湿关节炎患者进行问卷调查。内容包括患者个人资料、就诊及确诊时间、科室,随诊时间间隔以及改善病情抗风湿药（DMARDs）的应用情况。结果：类风湿关节炎药物治疗不规范,甲氨蝶呤是患者应用最多的DMARDs,占60％,其次为来氟米特（30％）、柳氮磺吡啶（5％）及羟氯喹（5％）。结论：51％以上的RA病人DMARDs治疗不规范,尤其是在县级基层医院。类风湿性疾病的规范治疗需要从早期诊断治疗,优化联合用药,个性化治疗,定期跟踪疗效等方面来规范。     

甲氨蝶呤联合来氟米特对类风湿关节炎患者炎症因子和免疫球蛋白的影响

目的:探讨甲氨蝶呤联合来氟米特对类风湿关节炎(RA)患者炎症因子和免疫球蛋白的影响。方法:选取于2016年6月-2017年10月期间我院收治的92例RA患者,根据乱数表法将患者随机分为对照组(n=46)与研究组(n=46)。对照组给予口服甲氨蝶呤片,研究组则在对照组的基础上联合来氟米特片治疗。两组均治疗3个月。比较两组患者临床疗效、临床症状改善情况,检测两组患者治疗前后炎症因子、免疫球蛋白水平,观察两组患者不良反应发生情况。结果:研究组患者治疗后的临床总有效率为95.65%(44/46),高于对照组患者的78.26%(36/46)(P0.05)。两组患者治疗后晨僵时间、压痛关节数、肿胀关节数均较治疗前降低,且研究组低于对照组(P0.05)。两组患者治疗后血细胞沉降率(ESR)、C反应蛋白(CRP)、白介素-8(IL-8)及肿瘤坏死因子(TNF-α)均较治疗前降低,且研究组低于对照组(P0.05)。两组患者治疗后免疫球蛋白G(Ig G)、免疫球蛋白A(Ig A)、免疫球蛋白M(Ig M)均较治疗前降低,且研究组低于对照组(P0.05)。两组患者不良反应发生率比较无差异(P0.05)。结论:甲氨蝶呤联合来氟米特治疗RA患者效果优于单用甲氨蝶呤治疗,可改善患者临床症状,同时降低Ig G、Ig A、Ig M以及炎症因子水平,无严重不良反应发生。     

阿达木单抗注射液联合白芍总苷治疗甲氨蝶呤不耐受型类风湿关节炎的临床疗效

目的:探讨阿达木单抗注射液联合白芍总苷治疗甲氨蝶呤不耐受风湿关节炎患者的临床疗效。方法:收集我院治疗的86例甲氨蝶呤不耐受的类风湿关节炎患者,随机分为实验组和对照组,每组43例。对照组患者给予阿达木单抗注射液治疗,实验组患者在对照组基础上给予白芍总苷胶囊治疗。观察并比较两组患者的晨僵时间、血沉(ESR)、类风湿因子(FR)以及临床疗效进行检测并比较。结果:与治疗前相比,治疗后两组患者的晨僵时间、血沉(ESR)、类风湿因子(FR)水平均下降(P0.05);与对照组相比,实验组患者的晨僵时间、血沉(ESR)、类风湿因子(FR)水平较低(P0.05),临床治疗有效率较高(P0.05)。结论:阿达木单抗注射液联合白芍总苷能够降低甲氨蝶呤不耐受的类风湿关节炎患者的ESR、FR水平,改善患者的临床症状,临床疗效较好。     

益生菌联合柳氮磺胺吡啶治疗溃疡性结肠炎的疗效观察

【摘 要】 目的 通过建立葡聚糖硫酸钠(DSS)诱导的急性期溃疡性结肠炎(UC)小鼠模型,观察嗜酸乳杆菌以及联合柳氮磺胺吡啶对小鼠溃疡性结肠炎(UC)的治疗作用,并检测Hsp70、Hsp27在肠黏膜的表达,探讨其可能的作用机制。方法　5% DSS 7 d建立急性UC动物模型。将60只BALB/c小鼠随机分为6组：正常对照组、模型组、阴性对照(生理盐水,NS)组、嗜酸乳杆菌组、柳氮磺胺吡啶组和嗜酸乳杆菌联合柳氮磺胺吡啶组,观察指标包括：疾病活动指数(DAI)、结肠黏膜肉眼改变及病理组织学积分;采用免疫组化SABC 法检测热休克蛋白(HSP70)和(HSP27)的表达量。结果 嗜酸乳杆菌可降低实验小鼠DAI积分和改善结肠组织损伤;与模型组、阴性对照组相比,嗜酸乳杆菌联合柳氮磺胺吡啶组的HSP70表达增加(P＜0.05),其中以嗜酸乳杆菌联合柳氮磺胺吡啶组效果最佳。结论 嗜酸乳杆菌和柳氮磺胺吡啶对小鼠溃疡性结肠炎都有治疗作用,且二者疗效相当;两药联合应用效果最佳。其机制可能与增加结肠黏膜HSP70的表达有关。     

甲氨蝶呤联合来氟米特治疗类风湿性关节炎的疗效及对血清 CRP、IL-8及 TNF-α水平的影响

目的:探讨甲氨蝶呤联合来氟米特治疗类风湿性关节炎(RA)的疗效及对患者血清C反应蛋白(CRP)、白细胞介素-8(IL-8)、肿瘤坏死因子-α(TNF-α)水平的影响。方法:选择2015年1月至2017年3月我院收治的RA患者106例,采用随机数字表法分为观察组(53例)和对照组(53例),两组均给予常规治疗,对照组加用甲氨蝶呤治疗,观察组在对照组的基础上加用来氟米特治疗,治疗4个月后,评价两组患者的临床疗效、临床症状,并对比两组患者血清CRP、IL-8及TNF-α水平变化。结果:治疗4个月后,观察组临床总有效率为96.23(51/53),高于对照组的79.25(42/53),差异有统计学意义(P0.05)。治疗前两组晨僵时间、压痛关节数、肿胀关节数等主要临床症状比较差异无统计学意义(P0.05);治疗4个月后,两组晨僵时间较治疗前缩短,压痛及肿胀关节数减少,且观察组晨僵时间短于对照组,压痛及肿胀关节数少于对照组(P0.05)。治疗前两组患者血清CRP、IL-8及TNF-α水平比较差异无统计学意义(P0.05);治疗4个月后,两组血清CRP、IL-8及TNF-α水平均较治疗前降低,且观察组低于对照组(P0.05)。治疗期间,观察组药物相关不良反应发生率为13.21(7/53),与对照组的11.32(6/53)比较,差异无统计学意义(P0.05)。结论:甲氨蝶呤联合来氟米特治疗RA的疗效理想,可显著改善患者的临床症状及降低血清CRP、IL-8及TNF-α水平。     

戈利木单抗联合雷公藤多甙对甲氨蝶呤治疗反应不佳活动性类风湿关节炎的效果及安全性分析

目的:分析戈利木单抗联合雷公藤多苷对甲氨蝶呤(MTX)治疗反应不佳活动性类风湿关节炎(RA)的临床效果及安全性。方法:选择MTX治疗反应不佳(MTX治疗超3个月,但应答不足)的活动性RA患者66例,按照随机数字表法分为对照组与试验组各33例,对照组单用雷公藤多苷治疗,试验组加用戈利木单抗治疗,测定两组治疗前后血沉(ESR)、C反应蛋白(CRP)、类风湿因子(RF)水平的变化,记录晨僵时间、关节肿胀数目、关节压痛数目,评定治疗效果,采用视觉模拟评分法(VAS)评定患者关节疼痛程度、患者对疾病总体症状的耐受情况,监测两组不良事件的发生情况。结果:(1)治疗后,两组ESR、CRP、RF均降低,与同组治疗前对比差异有统计学意义(P0.05),试验组ESR、CRP降低幅度高于对照组(P0.05);(2)治疗后,两组晨僵时间减少、关节肿胀及压痛数目均减少,与治疗前对比差异有统计学意义(P0.05),试验组各指标改善幅度均高于对照组(P0.05);(3)治疗后,两组VAS评分均降低,与治疗前对比差异有统计学意义(P0.05),试验组降低幅度高于对照组(P0.05);(4)试验组ACR50、ACR70所占比例均高于对照组(P0.05);(5)试验组、对照组不良反应发生率对比差异无统计学意义(P0.05)。结论:戈利木单抗联合雷公藤多苷治疗MTX反应不佳活动性RA疗效肯定,可下调患者ESR、CRP水平,缩短晨僵时间,显著改善患者症状,减轻关节疼痛程度,且安全性高。     

Comparison between penicillamine and sulphasalazine in rheumatoid arthritis: Leeds-Birmingham trial.

Sulphasalazine was first formulated by Svartz in the early 1940s, specifically for use as a remission inducing drug in rheumatoid arthritis. After the publication of an unfavourable trial, however, the drug was restricted to patients with ulcerative colitis. In the late 1970s sulphasalazine was re-examined in rheumatoid arthritis and favourable results reported in "open" trials. A double blind controlled trial was therefore conducted comparing enteric coated sulphasalazine and D-penicillamine in patients with active rheumatoid arthritis. A total of 63 patients were recruited in two centres; 31 were treated with sulphasalazine and 32 received penicillamine. After 16 weeks'' treatment both drugs had produced significant improvements in clinical score, pain score measured on a visual analogue scale, grip strength, Ritchie articular index, erythrocyte sedimentation rate, and serum C reactive protein concentration. Nausea was the major side effect in the sulphasalazine treated group. No potentially dangerous effects of sulphasalazine were encountered in contrast with those seen in the penicillamine group. The results suggest that sulphasalazine is an effective and safe drug capable of producing remissions in active rheumatoid arthritis. They also lend confidence to the use of preliminary "open" trials as a means of screening for remission inducing drugs in rheumatoid arthritis.     

Which component of sulphasalazine is active in rheumatoid arthritis?

Sulphasalazine is known to be effective as a second line agent in the treatment of rheumatoid arthritis. The two chemical constituents of sulphasalazine (sulphapyridine and 5-aminosalicylic acid) were assessed separately in the treatment of rheumatoid arthritis. Over 24 weeks sulphapyridine showed a pronounced second line effect comparable with sulphasalazine and with a similar toxicity profile, whereas 5-aminosalicylic acid showed only a weak first line effect. Thus sulphapyridine appears to be the active moiety responsible for the second line effect of sulphasalazine in rheumatoid arthritis. The efficacy of the antibacterial component of sulphasalazine yet again permits speculation about the role of a bacterial pathogen in the aetiopathogenesis of rheumatoid disease.     

Sulphasalazine in rheumatoid arthritis: a double blind comparison of sulphasalazine with placebo and sodium aurothiomalate.

Uncontrolled studies have suggested that sulphasalazine may be an effective second line agent in rheumatoid arthritis. Sulphasalazine was therefore compared with placebo and intramuscular sodium aurothiomalate in 90 patients with active rheumatoid arthritis. After six months'' treatment both sulphasalazine and sodium aurothiomalate had produced significant clinical and laboratory benefit, whereas placebo had produced no significant change in any variable. Thirteen patients stopped taking the placebo because of lack of effect whereas only two patients stopped taking sulphasalazine and one sodium aurothiomalate for this reason. The major toxicity encountered in the group treated with sulphasalazine was nausea or vomiting, or both; this may be related to slow acetylator phenotype. Sulphasalazine appears to be an effective second line agent, and further pharmacokinetic studies might prove useful in diminishing gastrointestinal side effects.     

Sulphasalazine for rheumatoid arthritis: toxicity in 774 patients monitored for one to 11 years.

Sulphasalazine is being used increasingly to treat rheumatoid arthritis, though its long term safety profile has not been established in this condition. The incidence and nature of adverse effects occurring in 774 patients with rheumatoid arthritis treated with sulphasalazine for periods ranging from one to 11 years were therefore noted. Altogether 205 of the patients stopped treatment permanently due to an adverse effect. One hundred and fifty six (76%) of these events occurred within three months and few beyond the first year. Most events were trivial and were self limiting after withdrawal of the drug; of the potentially more serious adverse effects, 33 (66%) occurred within three months of treatment. None of the patients died or suffered lasting ill effects. It is concluded that adverse effects of treatment with sulphasalazine are generally seen within three months; though regular monitoring is desirable during that period, thereafter few worrying problems occur.     

Sulphasalazine in ankylosing spondylitis: a double blind controlled study in 60 patients.

Sulphasalazine has been reported to be effective in ankylosing spondylitis with peripheral arthritis, but its efficacy in spondylitis is unknown. Thus 60 patients with active ankylosing spondylitis without peripheral arthritis or gastrointestinal symptoms were randomly allocated to one of two therapeutic groups. One group received 2 g sulphasalazine daily for six months and the other a placebo. Thirteen patients (six given placebo and seven given sulphasalazine) dropped out of the trial and were considered to be treatment failures. After six months'' follow up efficacy was rated as good or very good by 15 of the 30 patients given sulphasalazine and by only six of the 30 given placebo (p less than 0.02). Furthermore, in the patients given sulphasalazine the daily consumption of non-steroidal anti-inflammatory drugs, functional index, and plasma IgG concentrations had fallen significantly. These data suggest that sulphasalazine may be a safe and effective treatment for spondylitis in ankylosing spondylitis.     

Leflunomide suppresses TNF-induced cellular responses: effects on NF-kappa B, activator protein-1, c-Jun N-terminal protein kinase, and apoptosis

Leflunomide is a pyrimidine biosynthesis inhibitor that has recently been approved for treatment of rheumatoid arthritis. However, the mechanism of leflunomide's antiarthritis activity and is not fully understood. The critical role that TNF plays in rheumatoid arthritis led us to postulate that leflunomide blocks TNF signaling. Previously, we have demonstrated that leflunomide inhibits TNF-induced NF-kappaB activation by suppressing I-kappaBalpha (inhibitory subunit of NF-kappaB) degradation. We in this study show that leflunomide also blocks NF-kappaB reporter gene expression induced by TNFR1, TNFR-associated factor 2, and NF-kappaB-inducing kinase (NIK), but not that activated by the p65 subunit of NF-kappaB, suggesting that leflunomide acts downstream of NIK. Leflunomide suppressed TNF-induced phosphorylation of I-kappaBalpha, as well as activation of I-kappaBalpha kinase-beta located downstream to NIK. Leflunomide also inhibited TNF-induced activation of AP-1 and the c-Jun N-terminal protein kinase activation. TNF-mediated cytotoxicity and caspase-induced poly(ADP-ribose) polymerase cleavage were also completely abrogated by treatment of Jurkat T cells with leflunomide. Leflunomide suppressed TNF-induced reactive oxygen intermediate generation and lipid peroxidation, which may explain most of its effects on TNF signaling. The suppressive effects of leflunomide on TNF signaling were completely reversible by uridine, indicating a critical role for pyrimidine biosynthesis in TNF-mediated cellular responses. Overall, our results suggest that suppression of TNF signaling is one of the possible mechanisms for inhibitory activity of leflunomide against rheumatoid arthritis.     

Purine Metabolism and Clinical Status of Patients with Rheumatoid Arthritis Treated with Dipyridamole

The anti-inflammatory activities of methotrexate and sulphasalazine may be mediated by increases in endogenous adenosine levels. Since the vascular protective drug dipyridamole inhibits the uptake and metabolism of adenosine we have now tested this compound in patients with rheumatoid arthritis to assess its effects on their symptoms. Forty patients (aged 18–75 years) received dipyridamole 400 mg/day or placebo. The levels of adenosine and its major metabolites were determined by high performance liquid chromatography (HPLC) in blood samples taken at baseline and at monthly intervals during treatment for 6 months. After three months of treatment there was a significant reduction in the modified Health Assessment Questionnaire (mHAQ) score, but these effects were not maintained, and dipyridamole did not modify disease severity scores or the levels of adenosine and its metabolites. We conclude that the symptoms of rheumatoid arthritis were not modified by treatment with dipyridamole.     

Purine metabolism and clinical status of patients with rheumatoid arthritis treated with dipyridamole

The anti-inflammatory activities of methotrexate and sulphasalazine may be mediated by increases in endogenous adenosine levels. Since the vascular protective drug dipyridamole inhibits the uptake and metabolism of adenosine we have now tested this compound in patients with rheumatoid arthritis to assess its effects on their symptoms. Forty patients (aged 18-75 years) received dipyridamole 400 mg/day or placebo. The levels of adenosine and its major metabolites were determined by high performance liquid chromatography (HPLC) in blood samples taken at baseline and at monthly intervals during treatment for 6 months. After three months of treatment there was a significant reduction in the modified Health Assessment Questionnaire (mHAQ) score, but these effects were not maintained, and dipyridamole did not modify disease severity scores or the levels of adenosine and its metabolites. We conclude that the symptoms of rheumatoid arthritis were not modified by treatment with dipyridamole.     

Nimesulide Improves the Symptomatic and Disease Modifying Effects of Leflunomide in Collagen Induced Arthritis

Nimesulide is a COX-2 inhibitor used for symptomatic relief of rheumatoid arthritis. Leflunomide is an anti-pyrimidine used to manage the progression of rheumatoid arthritis. Herein we studied the influence of nimesulide and leflunomide combination in terms of disease symptoms and progression using collagen-induced arthritis model in mice, as a model for rheumatoid arthritis. Collagen induced arthritis was induced by immunization with type II collagen. Assessment of joint stiffness and articular hyperalgesia were evaluated using a locomotor activity cage and the Hargreaves method, respectively. Disease progression was assessed via arthritic index scoring, X-ray imaging, myeloperoxidase enzyme activity and histopathologic examination. Nimesulide induced only transient symptomatic alleviation on the top of decreased leucocytic infiltration compared to arthritis group. However, nimesulide alone failed to induce any significant improvement in the radiological or pathological disease progression. Leflunomide alone moderately alleviates the symptoms of arthritis and moderately retarded the radiological and pathological disease progression. Combination of nimesulide and leflunomide significantly improved symptomatic (analgesia and joint stiffness) and arthritic disease progression (radiological, pathological and Myeloperoxidase enzyme activity) in collagen induced arthritis animal model.