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对改善病情抗风湿药物和生物制剂治疗银屑病关节炎的疗效及毒性的系统评价和荟萃分析

A systematic review and meta-analysis of efficacy and toxicity of disease modifying anti-rheumatic drugs and biological agents for psoriatic arthritis.

作者信息

Ravindran V, Scott D L, Choy E H

机构信息

Sir Alfred Baring Garrod Clinical Trials Unit, Academic Department of Rheumatology, King's College London, London, UK.

出版信息

Ann Rheum Dis. 2008 Jun;67(6):855-9. doi: 10.1136/ard.2007.072652. Epub 2007 Sep 7.

Abstract

OBJECTIVE

Treatments for psoriatic arthritis (PsA) range from high-cost agents such as tumour necrosis factor (TNF) inhibitors evaluated in large randomised control trials (RCTs) and low-cost disease-modifying anti-rheumatic drugs (DMARDs) studied in less detail. We compared their efficacy and toxicity in a systematic review.

METHODS

We searched Medline, PubMed and EmBase (1966-2006) for RCTs in PsA. We included RCTs that were randomised, placebo-controlled, in English, involved current treatments and only enrolled PsA patients. Efficacy was assessed by the numbers of patients withdrawn for lack of effect; toxicity by withdrawals for adverse events. RCTs were compared using risk ratios (RR) with 95% confidence intervals (CI).

RESULTS

We identified 32 potentially relevant RCTs; 14 were excluded because they involved unused agents, were unblinded, were not placebo-controlled and enrolled patients with other diseases. 18 studies were included in the meta-analysis assessing DMARD monotherapy (11), DMARD combinations (one), TNF inhibitors (five) and alefacept (one). Treatment was more effective than placebo (RR = 0.35; 95% CI 0.25, 0.49) but caused more toxicity (RR = 2.33; 95% CI 1.61, 3.37). There was evidence that gold, sulfasalazine, leflunomide and TNF inhibitors were effective; gold and TNF inhibitors showed the largest effect sizes; TNF inhibitors had the best efficacy/toxicity ratio (number needed to harm/number needed to treat = 0.25); tolerability was least with gold and leflunomide.

CONCLUSIONS

Efficacy/toxicity ratios were highest with TNF inhibitors followed by leflunomide, gold and sulfasalazine. Gold, though effective, has excessive toxicity and sulfasalazine, though of low toxicity, was also relatively ineffective.

摘要

目的

银屑病关节炎(PsA)的治疗方法多样,从在大型随机对照试验(RCT)中评估的高成本药物如肿瘤坏死因子(TNF)抑制剂,到研究较少的低成本改善病情抗风湿药(DMARDs)。我们在一项系统评价中比较了它们的疗效和毒性。

方法

我们检索了Medline、PubMed和EmBase(1966 - 2006年)中关于PsA的RCT。纳入的RCT需为随机、安慰剂对照、英文发表、涉及当前治疗且仅纳入PsA患者。疗效通过因缺乏疗效而退出的患者数量评估;毒性通过因不良事件而退出的患者数量评估。使用风险比(RR)及95%置信区间(CI)对RCT进行比较。

结果

我们识别出32项可能相关的RCT;14项被排除,因为它们涉及未使用的药物、未设盲、未用安慰剂对照或纳入了患有其他疾病的患者。18项研究纳入荟萃分析,评估DMARD单药治疗(11项)、DMARD联合治疗(1项)、TNF抑制剂(5项)和阿法赛特(1项)。治疗比安慰剂更有效(RR = 0.35;95% CI 0.25,0.49),但毒性更大(RR = 2.33;95% CI 1.61,3.37)。有证据表明金制剂、柳氮磺胺吡啶、来氟米特和TNF抑制剂有效;金制剂和TNF抑制剂显示出最大的效应量;TNF抑制剂的疗效/毒性比最佳(伤害所需人数/治疗所需人数 = 0.25);金制剂和来氟米特的耐受性最差。

结论

TNF抑制剂的疗效/毒性比最高,其次是来氟米特、金制剂和柳氮磺胺吡啶。金制剂虽有效,但毒性过大;柳氮磺胺吡啶虽毒性低,但效果也相对较差。

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