生物制剂治疗类风湿关节炎的研究进展

类风湿关节炎（RA）是一类常见致残性自身免疫性疾病,传统的治疗药物主要有非甾体抗炎药、糖皮质激素等,但仍有部分病人病情无法控制,最终导致关节进行性破坏。近年来,多种生物制剂的出现为难治性RA的治疗带来了希望,可以有效控制风湿病活动和改善患者生活质量。该文就生物制剂在RA中的治疗进展作一综述。     

类风湿关节炎的药物治疗现状及进展

类风湿性关节炎（RA）是以侵犯关节为主的全身性自身免疫病。目前,治疗方案是以控制病情药物和生物制剂为主要的治疗手段。造血干细胞移植对于难治、重型的RA患者已经取得初步成果。基因治疗也将会给RA患者带来新的前景。目前对类风温关节炎的治疗多主张早期、规律、综合治疗,应尽早在3个月内选用（2～3）种DMARDs类药物;还可联合应用非甾体抗炎药或糖皮质激素;硫酸羟氯喹、柳氮磺胺吡啶、甲氨蝶呤三药联合是国际标准疗法,无效或效果不佳可适当加用或挟用来氟米特、生物制剂（单用或联合）。生物制剂治疗RA起效迅速。可与其它二线控制病情的抗风湿药物联用,具有不产生全身性免疫抑制、不良反应较少的特点,是治疗RA的一种趋势,较适合早期RA患者,可避免出现关节损毁及变形。     

2009年欧洲风湿病联盟关于类风湿关节炎治疗的指南

近年来,类风湿关节炎（RA）的诊治水平快速发展,特别是生物制剂的应用使RA的治疗备受关注。2008年,美国风湿病学会（ACR）通过数据库检索,海选文献,寻找证据,制定标准,再由专家委员会进行讨论,从科学性的角度出发提出了针对RA患者使用慢作用抗风湿病药物（disease—modifyingantirheu—maticdrugs,DMARDs）治疗的建议。     

难治性类风湿性关节炎诊断与 治疗新进展

欧洲风湿病协会联盟（EULAR）发布的类风湿性关节炎（RA）管理指南将满足规范治疗失败、病情确实活动、医患不满 意等3个标准的RA定义为难治性类风湿性关节炎（D2T RA）。现阶段RA的治疗药物主要有改善病情抗风湿药物（DMARD）、生物制 剂DMARD（bDMARD，如依那西普、阿达木单抗、英夫利昔单抗、托珠单抗和苏金单抗、CD20单抗等）、靶向合成DMARD（tsDMARD， 如乌帕替尼、巴瑞替尼、托法替布等），非药物治疗方法包括相关运动、教育、心理干预、自我管理等。D2T RA发病率有上升趋势，主要 原因有早期诊断困难，常有共病情况，治疗方案有限，疗效及患者依从性差等。本文就D2T RA的定义、分类、临床病理特征、预测因 素、治疗及管理策略等方面的研究进展作一述评，以期为临床提供参考。     

类风湿关节炎和强直性脊柱炎的生物治疗与关节腔灌注治疗进展

类风湿关节炎（RA）是一种以滑膜关节炎症和破坏为特征的自身免疫性疾病.随着其发病机制和相关细胞因子研究的深入,对RA治疗的研究主要集中在新型生物制剂的发展上.强直性脊柱炎（AS）是一种慢性炎性疾病,主要侵犯中轴骨骼,以骶髂关节炎为标志,AS的药物治疗一直为风湿病学家所关注.该文就目前新型生物制剂的发展情况与关节腔灌注治疗进展进行综述.     

英夫利西单抗治疗类风湿关节炎患者生存质量研究

类风湿关节炎（rheumatoid arthritis,RA）是一类以关节炎为主要临床表现的系统性自身免疫病,目前尚无特异的根治手段,致残率高。英夫利西单抗（商品名类克）,是一种新型的生物制剂,主要用于RA、强直性脊柱炎（AS）和克隆病等的治疗。本文研究经英夫利西单抗治疗后,RA患者的生存质量改变情况,现报告如下。     

类风湿关节炎的中医药治疗进展

类风湿关节炎（Rheum atoid Arthritis,RA）是一种以慢性、多发性、对称性关节肿痛为主要表现的常见全身性自身免疫疾病,是医学界的疑难症之一。目前国内外治疗RA尚无特效疗法,西医多采用非甾体类抗炎药、激素、慢作用抗风湿药物、生物制剂等,均有较大不良反应。而中医药在治疗RA方面因其毒副作用小、疗效显著体现了其优越性,现将近几年有关研究概况综述如下。     

强骨胶囊治疗82例类风湿关节炎继发骨质疏松患者的疗效评估

背景：类风湿关节炎（rheumatoid arthritis,RA）是一种常见的慢性、炎性、系统性自身免疫性疾病,骨质疏松是其常见并发症。目的：探讨强骨胶囊对RA患者骨密度（bone mineral density,BMD）及继发性骨质疏松的影响。设计、场所、对象和干预措施：2010年1月-2012年12月,将就诊于上海市光华中西医结合医院的82例RA伴骨质疏松患者分为治疗组（42例）和对照组（40例）,治疗组给予强骨胶囊和两种缓解病情的抗风湿药物（disease—modifying antirheumatic drug,DMARD）治疗,对照组仅给予两种常规DMARD药物治疗,治疗疗程为6个月。主要结局指标：治疗前后,检测骨密度、C-反应蛋白（（C-reactive protein,CRP）、血沉（erythrocyte sedimentation rate,ESR）、血钙、血磷、碱性磷酸酶（alkaline phosphatase,ALP）等指标。结果：与治疗前比较,治疗6个月后治疗组患者ALP活性、血钙浓度较治疗前显著升高,CRP、ESR水平下降,腰椎、股骨和桡骨的BMD增加,差异有统计学意义（P〈0．05）;对照组患者治疗后的ALP活性和BMD无明显变化。与对照组比较,治疗后治疗组患者的ALP活性、血钙浓度增加,BMD增高。结论：强骨胶囊能通过增加RA患者的血钙浓度和ALP活性,增加BMD,骨改善骨质疏松。     

益赛普联合甲氨蝶呤治疗类风湿关节炎护理体会

目的探讨生物制剂益赛普联合甲氨蝶呤治疗类风湿关节炎（RA）的护理体会。方法选择40例RA患者,采用生物制剂益赛普联合甲氨蝶呤治疗,并落实护理措施,做好专科护理。根据关节功能指数以及简明健康调查量表,比较用药前及用药和护理12周后患者关节肿胀数、关节压痛数、晨僵时间,类风湿关节炎临床活动评分（DAS28评分）,生活质量评分（生理功能、精神健康、社会功能评分）。结果治疗后患者关节肿胀数、关节压痛数、晨僵时间和DAS28评分均较治疗前改善,生活质量评分均明显优于治疗前,差异均有统计学意义（均P＜0.05）。结论益赛普联合甲氨蝶呤治疗RA患者时,落实好专科护理,做好心理护理及健康宣教,能取得满意疗效。     

治疗类风湿关节炎骨破坏的生物制剂研究进展

类风湿关节炎（rheumatoidarthritis,RA）是一种病因复杂的自身免疫炎性疾病,以慢性、对称性、多滑膜关节炎和关节外病变为主要表现,骨破坏可发生在疾病活动的早期。并逐步进展,是导致RA中晚期患者劳动能力丧失的主要原因之一．因此预防和阻断RA骨破坏也成为了治疗目标。随着研究深入,许多与RA骨破坏相关的细胞因子、信号通路及细胞被发现。针对于此,最近用于治疗RA骨破坏的相关生物制剂研究也在不断被推进,许多有价值的实验研究结果被报道,故本文试图在RA骨破坏机制基础上探讨生物制剂实验研究方面的最新进展。     

新型生物制剂在炎症性肠病中的临床应用：现状与未来

近年来,抗肿瘤坏死因子α制剂等生物制剂在炎症性肠病（IBD）治疗方面的应用逐年增多,但由于其安全性较低且继发性失应答率较高等,临床应用受限。随着新型生物制剂不断涌现,IBD的治疗进入生物制剂时代,而新型生物制剂有可能成为IBD药物治疗的主体。本文就新型生物制剂抗黏附分子制剂、抗白介素12/23因子制剂及JAK抑制剂在IBD中的应用现状、作用机制、疗效、安全性及应用前景进行评述,以期为新型生物制剂在IBD患者中的规范、合理应用提供参考。     

糖尿病肾病治疗新进展

糖尿病肾病是导致终末期肾病的最常见原因之一,其发生率持续增加,将近1/3的糖尿病患者发展为糖尿病肾病.早期诊断及有效控制血糖、血压、血脂等措施在减缓糖尿病肾病的发展方面显碍尤为重要.最近,不断有新的刳剂被认为对糖尿病肾病有延缓作用,包括糖化终产物抑制和裂解剂、蛋白激酶C抑制物、氨基葡聚糖、内皮素受体拮抗剂、抗纤维化剂及血管内皮生长因子抑制剂等.针对糖尿病发病机制的各个环节进行综合治疗,是降低糖尿病肾病发病率的研究方向.该文就常用的糖尿病肾病治疗方法及潜在的治疗进展予以综述.     

B-Raf激酶抑制剂的研究进展

原癌基因B-Raf存在于多种肿瘤细胞中,尤其在黑色素瘤和甲状腺癌中。选择性B-Raf激酶抑制剂vemurafenib的上市引起了人们对此类抑制剂的广泛关注。通过分析vemurafenib与B-Raf激酶的结合模式,人们对B-Raf激酶抑制剂提出了新的分类。依据此分类,本文对蛋白质晶体数据库(PDB)出现的B-Raf激酶抑制剂进行了分析,比较每种类型抑制剂的作用模式,分析其构效关系,并对Raf激酶抑制剂的未来进行了展望。     

非异羟肟酸类肿瘤坏死因子转化酶抑制剂的研究进展

类风湿性关节炎属自身免疫性疾病，全球约有1%～2%的人群受该病困扰。肿瘤坏死因子转化酶(TACE)是治疗类风湿性关节炎的潜在的靶点，当前TACE抑制剂主要分为异羟肟酸类和非异羟肟酸类抑制剂两类。本文对近几年来出现的新型非异羟肟酸类TACE小分子抑制剂进行介绍，使读者对当前高活性、高选择性非异羟肟酸类TACE抑制剂的发展和设计研究现状有个总体的了解。     

Update of epidermal growth factor receptor-tyrosine kinase inhibitors in non-small-cell lung cancer

Lung cancer is the leading cause of cancer-related death in the world. Prior to the era of targeted therapy, platinum-based doublet chemotherapy was the first-line therapy of choice for patients with metastatic non-small-cell lung cancer (NSCLC). The availability of agents that target epidermal growth factor receptor (EGFR)-tyrosine kinase, as well as inhibitors against anaplastic lymphoma kinase (ALK) gene rearrangement or ROS-1 gene rearrangement product, has provided promising clinical benefits in specific subpopulations of NSCLC. At present, only first-generation EGFR-tyrosine kinase inhibitors (TKIs) (erlotinib and gefitinib) are available for clinical use. Second-generation irreversible EGFR-TKIs, such as afatinib, are still in clinical trials. In current clinical practice, EGFR-TKI is the first-line treatment of choice for metastatic NSCLC patients with tumor EGFR mutation or as salvage therapy in NSCLC patients who received systemic chemotherapy previously. Platinum-based doublet chemotherapy continues to be the standard of care for those treatment-naïve patients with EGFR wild -type tumor or unknown EGFR status. Even though all investigators agree with the use of EGFR-TKI as the first-line treatment in tumor EGFR-mutated patients, only 10–30% of NSCLC patients have mutated EGFR, and there was no obvious survival difference when EGFR-TKIs were used in a second-line setting versus a first-line treatment in EGFR-mutated patients. Thus, the molecular complexity of lung cancer emphasizes the need for optimizing treatment by seeking a more personalized approach to care, including searching for driver oncogenes, managing the emergence of resistance and overcoming that resistance, and optimizing the sequence of treatment. Numerous other novel targeted agents are now in clinical development, including new agents targeting novel pathways and those that may have the potential to overcome the limitations or resistance associated with currently available EGFR-TKIs. In this report, we review the clinical data of EGFR-TKIs as molecular-targeted therapies in NSCLC.     

Prevalent and emerging therapies for osteoporosis

Osteoporosis and fractures associated with it constitute a real and serious socio-medical problem, which only recently has come to the forefront of social consciousness. With increasing number of exservicemen and their dependents, osteoporosis management has become very important in our setup. Currently available pharmacological therapies for prevention of fragility fractures are limited in scope, efficacy and acceptability to patients. Oral bisphosphonates are the standard treatment for osteoporosis which are associated with significant gastrointestinal side effects and thus poor patient compliance. Newer regimens, including intravenous (IV) formulations of bisphosphonates, have successfully come in vogue with greater patient compliance and equal or better benefits. The real need in osteoporosis treatment is for additional anabolic drugs. The only currently approved anabolic agent for treating osteoporosis is teriparatide (recombinant human parathyroid hormone 1–34), which stimulates new bone formation. Considerable efforts are being made to develop new, more effective treatment for osteoporosis. These novel drugs under trial include those primarily inhibiting osteoclastic bone resorption (like bisphosphonates) such as inhibitors of receptor activator of nuclear factor-kappa B ligand (RANKL) signalling, cathepsin K inhibitors, c-Src kinase inhibitors, integrin inhibitors, chloride channel inhibitors and the drugs with osteo-anabolic actions such as orally active parathyroid hormone (PTH) analogues, calcium sensing receptor antagonists, PTH-related peptide analogues and agents that induce osteoblast anabolism via pathways involving key, recently identified, molecular targets (wnt low-density lipoprotein receptor-related protein-5 signalling; sclerostin antibodies).     

Prevalent and Emerging Therapies for Osteoporosis

Osteoporosis and fractures associated with it constitute a real and serious socio-medical problem, which only recently has come to the forefront of social consciousness. With increasing number of exservicemen and their dependents, osteoporosis management has become very important in our setup. Currently available pharmacological therapies for prevention of fragility fractures are limited in scope, efficacy and acceptability to patients. Oral bisphosphonates are the standard treatment for osteoporosis which are associated with significant gastrointestinal side effects and thus poor patient compliance. Newer regimens, including intravenous (IV) formulations of bisphosphonates, have successfully come in vogue with greater patient compliance and equal or better benefits. The real need in osteoporosis treatment is for additional anabolic drugs. The only currently approved anabolic agent for treating osteoporosis is teriparatide (recombinant human parathyroid hormone 1–34), which stimulates new bone formation. Considerable efforts are being made to develop new, more effective treatment for osteoporosis. These novel drugs under trial include those primarily inhibiting osteoclastic bone resorption (like bisphosphonates) such as inhibitors of receptor activator of nuclear factor-kappa B ligand (RANKL) signalling, cathepsin K inhibitors, c-Src kinase inhibitors, integrin inhibitors, chloride channel inhibitors and the drugs with osteo-anabolic actions such as orally active parathyroid hormone (PTH) analogues, calcium sensing receptor antagonists, PTH-related peptide analogues and agents that induce osteoblast anabolism via pathways involving key, recently identified, molecular targets (wnt low-density lipoprotein receptor-related protein-5 signalling; sclerostin antibodies).Key Words: Osteoporosis, Prevalent, Emerging therapies     

类风湿关节炎常用药物治疗方案及进展

类风湿性关节炎(RA)是一种以非化脓性增生性滑膜炎为主的对称性自身免疫性疾病,最初会影响小关节,逐渐发展为大关节,最后影响皮肤、眼睛、心脏、肾脏和肺部.RA发病机制特殊,目前虽诊疗手段繁多,却暂无完美诊疗手段.现有的用于治疗RA的药物诸如甲氨蝶呤类慢性抗风湿类药物(DMARDs)、类固醇(GC)、非类固醇消炎药(NSA...     

肠促胰岛素类似物和DPP-Ⅳ抑制剂在2型糖尿病治疗中的作用

肠促胰岛素类似物(incretin mimetics)是一类具有多种抗高血糖作用的新型降糖药物,它模拟胰升糖素样肽(GLP)-1的作用;二肽基肽酶(DPP-Ⅳ)抑制剂抑制GLP-1的降解。这两类药物的作用机制为:增加葡萄糖依赖的胰岛素分泌;抑制不适当的胰高血糖素分泌增多;增强胰岛素敏感性;减缓胃的排空;和抑制食欲。研究显示,肠促胰岛素类似物和DPP-Ⅳ抑制剂还具有促进胰岛β细胞新生的作用,可能会成为未来2型糖尿病(T2DM)治疗领域的新药。目前,几种肠促胰岛素类似物和DPP-Ⅳ抑制剂正在进行T2DM治疗的末期临床试验。