Cardiovascular outcomes of patients with rheumatoid arthritis prescribed disease modifying anti-rheumatic drugs: a review

Introduction: Rheumatoid arthritis (RA) is associated with a heightened risk of cardiovascular disease (CVD), with both traditional CV risk factors and inflammation contributing to this risk.

Areas covered: This review highlights the burden of CVD in RA and associated traditional CV risk factors, including the complexity of dyslipidemia in RA and the so-called ‘lipid paradox.’ Furthermore, the recognized RA-disease-specific factors associated with higher risk of CVD and the role of systemic inflammation in the pathogenesis of CVD in RA will be addressed. With the advent of biologic and targeted synthetic therapies in the treatment of RA, the effect of conventional and newer generation disease modifying anti-rheumatic therapies (DMARDs) on CV risk and associated risk factors will also be discussed.

Expert opinion: Identifying the RA phenotype at greatest risk of CVD, understanding the interplay of increased traditional risk factors, common inflammatory processes and RA-specific factors, and personalized use of DMARDs according to disease phenotype and comorbidity to reduce this risk are key areas for future research.     

Mixed treatment comparison of efficacy and tolerability of biologic agents in patients with rheumatoid arthritis

Abstract

Objective:

To determine the comparative efficacy and tolerability of abatacept and tumor necrosis factor inhibitors (TNFi) in patients with rheumatoid arthritis (RA) and inadequate response to conventional disease modifying anti-rheumatic drugs (DMARDs).     

Clinical utility of therapeutic drug monitoring in biological disease modifying anti-rheumatic drug treatment of rheumatic disorders: a systematic narrative review

Introduction: Biological Disease Modifying Anti-Rheumatic Drugs (bDMARDs) have improved the treatment outcomes of inflammatory rheumatic diseases including Rheumatoid Arthritis and spondyloarthropathies. Inter-individual variation exists in (maintenance of) response to bDMARDs. Therapeutic Drug Monitoring (TDM) of bDMARDs could potentially help in optimizing treatment for the individual patient.

Areas covered: Evidence of clinical utility of TDM in bDMARD treatment is reviewed. Different clinical scenarios will be discussed, including: prediction of response after start of treatment, prediction of response to a next bDMARD in case of treatment failure of the first, prediction of successful dose reduction or discontinuation in case of low disease activity, prediction of response to dose-escalation in case of active disease and prediction of response to bDMARD in case of flare in disease activity.

Expert opinion: The limited available evidence does often not report important outcomes for diagnostic studies, such as sensitivity and specificity. In most clinical relevant scenarios, predictive value of serum (anti-) drug levels is absent, therefore the use of TDM of bDMARDs cannot be advocated. Well-designed prospective studies should be done to further investigate the promising scenarios to determine the place of TDM in clinical practice.     

A population model of early rheumatoid arthritis disease activity during treatment with methotrexate,sulfasalazine and hydroxychloroquine

Aims

To develop a population model describing the disease activity (DAS28) time course in patients with early rheumatoid arthritis (RA) treated with triple disease-modifying anti-rheumatic drug (DMARD) therapy (methotrexate, sulfasalazine and hydroxychloroquine).

Methods

DAS28 was obtained in 263 patients with early RA from initiation of therapy until 60 weeks. Using nonmem®, base models (DAS28 vs. time) and covariate influences were investigated for the population.

Results

The best model was an exponential model of DAS28 vs. time that was additive to baseline DAS28, with covariance between parameters, and a combined residual error model. Age and patient smoking history were covariates significantly affecting response to therapy. Population estimates were baseline DAS28 (5.7), extent of change in DAS28 (−2.8) and the half-life of disease activity (6.2 weeks; time to steady disease state achieved within approximately 30 weeks). Older individuals exhibited more severe baseline DAS28, described by a power function centred around 57 years (baseline DAS28 for 40- and 70-year-old patients were 5.4 vs. 5.8, respectively) and current smokers took longer to achieve a steady disease state (approximately 50 weeks). There was considerable within-patient random variability in DAS28 over time (empirical 90% CI for DAS28 in a population typical patient at 60 weeks: 1.8, 4.2 with median value of 2.8).

Conclusions

This is the first report of a disease activity model for early RA treated with triple DMARD therapy. Smoking and age were identified as covariates.     

雪莲治疗类风湿性关节炎疗效系统评价

目的系统评价雪莲治疗类风湿性关节炎的临床疗效。方法计算机检索MEDLINE（1996年至2005年11月）、EMBASE（1984年至2005年11月）、Cochrane临床对照试验资料库（2005年第4期）、中国Cochrane中心临床对照实验资料数据库、中国生物医学文献数据库（1978年至2005年11月）,手工检索纳入试验的所有中文及外文文献及相关文献,并逐个进行方法学质量评价,采用RevMan4.2.7软件进行Meta分析。结果共纳入2个半随机对照试验（198例患者）,结果显示,①治愈率：1个研究报道了与湿热麻痹剂比较,治疗前后差异无统计学意义[RR1.81,95%CI（0.40,8.81）];②总有效率：2个研究,与湿热麻痹剂或吲哚美辛比较,治疗前后差异无统计学意义[RR1.21,95%CI（1.00,1.46）;RR 1.23,95%CI（1.02,1.48）]。结论现有的有限证据表明,无法得出其能改善类风湿性关节炎的治愈率、总有效率或病死率等的结论;需要更多设计良好的随机、双盲、安慰剂对照试验加以证实。     

短期应用改善病情抗风湿药治疗类风湿关节炎出现肝功能异常的临床特点

目的:观察短期应用改善病情抗风湿药(disease-modifying antirheumatic drug, DMARD)治疗类风湿关节炎致肝功能异常发生率及其特点。方法:分析2016年6月至2019年6月初诊首次应用DMARD治疗的类风湿关节炎患者472例,观察患者2周后肝功能异常的发生情况以及临床特点。结果:472例患者完成2周治疗后发生肝功能异常54例(11.44%);应用DMARD单药肝功能异常发生率为12.06%(34/282),其中氨甲蝶呤发生率最高,为22.73%(10/44);DMARD联合用药肝功能异常发生率为10.53%(20/190),氨甲蝶呤联用柳氮磺吡啶发生率最高,为22.22%(2/9);发生肝功能异常者的血沉高于无肝功能异常者(P=0.016);应用氨甲蝶呤发生肝功能异常的风险最大(OR=1.902),羟氯喹可减少肝功能异常的发生(OR=0.325)。结论:应用DMARD治疗类风湿关节炎短期内即可导致肝功能异常,可能与个体敏感性及药物选择有关。     

沙利度胺联合其他药品治疗类风湿关节炎的系统评价

目的 系统评价沙利度胺联合其他药品治疗类风湿关节炎的有效性与安全性。方法 检索2017年9月1日前发表在PubMed、Medline、Web of Science及中国知网（CNKI）、中国生物医学文献数据库（CBM）、维普数据库（VIP）、万方数据库中相关的随机对照试验（RCTs）,应用State 14.0软件进行Meta-分析。结果 共纳入15篇相关文献,累计1 246例患者。Meta-分析结果显示,联用沙利度胺组在有效率（OR=2.71,95% CI=1.87~3.93,P<0.05）、关节肿胀数（OR=1.68,95% CI=0.99~2.37,P<0.05）、关节压痛数（OR=2.22,95% CI=1.31~3.14,P<0.05）、红细胞沉降率（OR=12.93,95% CI=10.26~15.60,P<0.05）等方面疗效均优于对照组。在不良反应发生率方面,联用沙利度胺组与对照组比较无显著性差异（OR=0.93,95% CI=0.66~1.32,P>0.05）。结论 联用沙利度胺在类风湿关节炎的治疗中有积极作用。     

糖皮质激素联合慢作用抗风湿药治疗类风湿关节炎的临床观察

目的观察小剂量糖皮质激素联合慢作用抗风湿药物治疗类风湿关节炎的临床疗效。方法将76例初发类风湿关节炎患者随机分为小剂量糖皮质激素联合慢作用抗风湿药物组(激素联合治疗组,共38例)及慢作用抗风湿药物治疗组(对照组,共38例),两组均给予慢作用抗风湿药物,其中激素联合治疗组另给予小剂量糖皮质激素,对照组给予洛索洛芬钠治疗,全部患者在治疗前与治疗后2、4、12、24周检测临床指标、免疫学指标及足跟骨密度值。结果治疗后联合治疗组VAS评分、DAS28评分及ESR、CRP水平与治疗前、同期对照组相比,差异均有统计学意义(P<0.05)。治疗24周,两组足跟骨密度值比较差异无统计学意义(P>0.05)。结论小剂量糖皮质激素联合慢作用抗风湿药物可在短期内明显缓解临床症状,降低炎性指标,且短期内未见增加骨质疏松风险。     

类风湿关节炎治疗药物的研究进展

近年来,类风湿关节炎治疗药物的研发有较大进展。肿瘤坏死因子-α(TNF-α)抑制剂、白介素(IL)抑制剂、蛋白酶抑制剂和改善病情抗风湿药都有新品种出现,并且在临床广泛应用。本文对上述药物的临床疗效和安全性做一综述。     

类风湿性关节炎治疗药物研究进展

类风湿性关节炎（RA）是一种常见的慢性全身性自身免疫性疾病,其病情错综复杂,发病机制尚未完全明确,目前普遍认为个体遗传易感性、环境因素和失调的免疫反应与RA发病有关。主要就RA的发并机制及其治疗药物研发进展进行综述。     

关节镜与切开术治疗类风湿性关节炎的效果比较

目的比较关节镜与切开术治疗类风湿性关节炎的效果。方法选择2009年10月～2011年10月于本院就诊的膝关节类风湿性关节炎患者86例,根据患者意愿分为切开术组和关节镜组。切开术组43例患者采用切开直视滑膜切除术,关节镜组43例患者采用关节镜下滑膜切除术,比较两组的住院时间、术中出血量、术后功能锻炼时间。所有患者均随访6～24个月,采用膝关节HSS评分,对膝关节功能恢复情况进行比较。结果关节镜组恢复功能锻炼时间、平均住院时间均短于切开术组,术中平均出血量少于切开术组,两组差异有统计学意义（P〈0．05）。随访6～24个月,关节镜组与切开术组优良率分别为80．00％和83．67％,两组膝关节功能恢复情况差异无统计学意义（P〉0．05）。结论关节镜与切开术均可有效恢复患者的关节功能,是治疗类风湿性关节炎的有效方法。关节镜较切开术具有创伤小、出血少、住院时间短的优点．对具备关节镜适廊证的患者麻优先选择关节镜．     

The treatment of juvenile arthritis

Until recently, two different classification systems for juvenile arthritis (JA) were utilised, each with its own terminology and subclassification (Table 1) [1]. It has been recognised that particularly within the polyarticular and pauci-articular groups, many distinct subsets exist each with a different prognosis. As a result, a new classification system for JA has been developed (Table 2) [2]. It is hoped that this will allow more accurate assessment of incidence and aetiology of the various subtypes in future generations and in time will allow therapy to be targeted at those most likely to achieve benefit. Since there is a new classification system for JA, the vast majority of published clinical studies were performed using the old classification system. For the purposes of this review, unless otherwise stated, the American College of Rheumatology classification will be used. This is outlined in Table 1 with clinical features of the major subtypes described in Table 3. This review will cover current best practice and discuss future directions for research using the recent advances in the treatment of rheumatoid arthritis (RA) as a model.     

萘丁美酮和尼美舒利治疗类风湿关节炎疗效和安全性的比较

目的 :比较 2种非甾类消炎药 (NSAIDs)萘丁美酮和尼美舒利治疗类风湿关节炎 (RA)的疗效和安全性。方法 :6 2例活动性RA病人分为 2组 ,萘丁美酮组 (治疗组 ) 30例 ,给予萘丁美酮 5 0 0mg ,po ,bid ;尼美舒利组 (对照组 ) 32例 ,给予尼美舒利10 0mg ,po ,bid。 2组均给药 4wk。受试前后观察临床和实验室指标的变化。结果 :萘丁美酮组总有效率为 87% ,尼美舒利组总有效率为 83% ,P >0 .0 5。与萘丁美酮治疗有关的不良反应包括 :恶心、胃烧灼感、反酸和嗜睡各 1例 ,不良反应率13% ;尼美舒利组不良反应率为 19% ,P >0 .0 5。结论 :萘丁美酮对RA的疗效和不良反应的发生率均与尼美舒利相似 ,是一种较为有效、安全且服用方便的NSAIDs。     

Review of treatment response in rheumatoid arthritis: assessment of heterogeneity

Abstract

Objective:

Rheumatoid arthritis (RA) is a chronic, systemic, progressive, inflammatory disorder. The primary goals of treatment in RA are to reduce the signs and symptoms of disease, prevent progression of joint damage and improve patients’ physical function. Patients with different sociodemographic characteristics, varying degrees of severity of illness, and comorbidities tend to exhibit differential response to treatment. The purpose of this review was to identify a broad set of factors that are associated with and/or predictive of RA treatment response and determine those that warrant further research.     

高频超声在抗风湿药物治疗类风湿性关节炎疗效评估中的价值探讨

目的观察小剂量糖皮质激素联合抗风湿药物治疗类风湿性关节炎(RA)的疗效,并探讨高频超声在RA疗效评估中的价值。方法收集我院2018年3月至2019年1月收治的初诊RA患者80例,随机分成观察组和治疗组,每组40例。对照组给予雷公藤联合甲氨蝶呤治疗;观察组在此基础上,给予强的松口服。两组患者在治疗前及治疗1个月、3个月、6个月时高频超声检测双手指及腕关节滑膜厚度,同时检测血ESR、CRP指标及评估DAS28评分,观察两组各项指标变化情况。结果治疗前两组上述各项指标差异无统计学意义(P<0.05),治疗后在同一时点,两组各项指标与治疗前比较均下降,其中观察组滑膜厚度以及腕关节血流分级、ESR、CRP、DAS28评分等各项指标与治疗前比较差异均有统计学意义(P<0.05)。观察组上述各项指标较对照组均明显下降,两组比较差异有统计学意义(P<0.05)。结论小剂量糖皮质激素联合抗风湿药物治疗RA疗效确切,同时高频彩超能实时反映关节滑膜变化,在RA治疗腕关节疗效评估中具有一定的价值。     

小剂量糖皮质激素联合DMARD治疗类风湿关节炎的临床研究

目的探讨小剂量糖皮质激素联合慢作用抗风湿药（DMARD）治疗类风湿关节炎（RA）的疗效。方法将60例RA患者随机分为小剂量糖皮质激素联合DMARD治疗组（30例,联合组）和单纯应用DMARD治疗组（30例,对照组）。两组均用DMARD治疗,联合组另给予糖皮质激素：强的松10 mg,1次/d口服,所有患者在治疗前和治疗后12周,均检测临床和免疫学指标。结果联合组治疗后与治疗前、对照组治疗后比较,临床DAS28评分、ESR、CRP、IL-6水平差异有统计学意义（P〈0.05）。结论小剂量糖皮质激素联合DMARD可有效改善患者关节肿痛的症状,明显抑制炎症反应,控制病情的进展。     

英夫利昔单抗治疗类风湿关节炎的临床研究

目的探讨英夫利昔单抗治疗类风湿关节炎的临床疗效,为临床合理用药提供参考。方法回顾性分析我院风湿免疫科2013年10月至2015年6月收治的30例患者应用英夫利昔单抗治疗类风湿关节炎的情况,观察患者治疗前后症状、体征及实验室检查等情况。结果治疗后患者的血沉和CRP明显降低,病情活动情况明显减轻。30例患者中,1例出现局部注射反应,2 d内可自动消失。其余患者未发现明显不良反应。结论英夫利昔单抗能明显改善RA等风湿免疫疾病的炎症反应,抑制关节破坏进展,改善患者的临床表现及预后。