聚乙二醇化赛妥珠单抗治疗轻至中度活动性类风湿关节炎患者：CERTAIN双盲、随机、安慰剂对照试验

Certolizumab pegol in rheumatoid arthritis patients with low to moderate activity: the CERTAIN double-blind, randomised, placebo-controlled trial.

作者信息

Smolen J S, Emery P, Ferraccioli G F, Samborski W, Berenbaum F, Davies O R, Koetse W, Purcaru O, Bennett B, Burkhardt H

机构信息

Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, and 2nd Department of Medicine, Hietzing Hospital, Vienna, Austria.

Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Chapel Allerton Hospital, Leeds, UK NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust, Leeds, UK.

出版信息

Ann Rheum Dis. 2015 May;74(5):843-50. doi: 10.1136/annrheumdis-2013-204632. Epub 2014 Jan 15.

DOI:10.1136/annrheumdis-2013-204632

PMID:24431394

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4392224/

Abstract

OBJECTIVES

This 52-week, randomised, double-blind phase IIIb study assessed efficacy and safety of certolizumab pegol (CZP) as add-on therapy to non-biologic disease-modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis (RA) patients with low to moderate disease activity, and stopping therapy in patients in sustained remission.

METHODS

Patients were randomised 1:1 to CZP (400 mg at weeks 0, 2 and 4, then 200 mg every 2 weeks) or placebo (every 2 weeks) plus current non-biologic DMARDs. At week 24, patients who achieved the primary endpoint of Clinical Disease Activity Index (CDAI) remission at both weeks 20 and 24 stopped study treatment and continued in the study until week 52.

RESULTS

Of 194 patients (CZP=96; placebo=98), >90% had moderate disease activity at baseline. Significantly more CZP patients met the primary endpoint than placebo patients (week 20 and 24 CDAI remission rates: 18.8% vs 6.1%; p≤0.05). At week 24, 63.0% vs 29.7% of CZP versus placebo patients (p<0.001) achieved LDA. Disease activity score (ESR) based on 28-joint count and Simplified Disease Activity Index remission rates were also significantly higher with CZP versus placebo (19.8% vs 3.1%; p≤0.01 and 14.6% vs 4.1%; p≤0.05). CZP patients reported improvements in physical function versus placebo (mean Health Assessment Questionnaire-Disability-Index change from baseline: CZP, -0.25 vs placebo, -0.03; p≤0.01). During the period following withdrawal of CZP or placebo, only 3/17 prior CZP patients and 2/6 prior placebo patients maintained CDAI remission until week 52, but CZP reinstitution allowed renewed improvement. Adverse and serious adverse event rates were comparable between CZP and placebo groups.

CONCLUSIONS

Addition of CZP to non-biologic DMARDs is an effective treatment in RA patients with predominantly moderate disease activity, allowing low-disease activity or remission to be reached in a majority of the patients. However, the data suggest that CZP cannot be withdrawn in patients achieving remission.

TRIAL REGISTRATION NUMBER

NCT00674362.

摘要

目的

这项为期52周的随机双盲IIIb期研究评估了聚乙二醇化赛妥珠单抗（CZP）作为低至中度疾病活动度类风湿关节炎（RA）患者非生物改善病情抗风湿药（DMARDs）的附加疗法的疗效和安全性，以及持续缓解患者停药后的情况。

方法

患者按1:1随机分组，接受CZP（第0、2和4周400mg，然后每2周200mg）或安慰剂（每2周一次）加当前非生物DMARDs治疗。在第24周时，在第20周和第24周均达到临床疾病活动指数（CDAI）缓解这一主要终点的患者停止研究治疗，并继续留在研究中直至第52周。

结果

194例患者（CZP组96例；安慰剂组98例）中，>90%在基线时疾病活动度为中度。达到主要终点的CZP组患者显著多于安慰剂组患者（第20周和第24周CDAI缓解率：18.8%对6.1%；p≤0.05）。在第24周时，CZP组和安慰剂组分别有63.0%和29.7%的患者达到低疾病活动度（LDA）（p<0.001）。基于28个关节计数的疾病活动评分（ESR）和简化疾病活动指数缓解率在CZP组也显著高于安慰剂组（19.8%对3.1%；p≤0.01和14.6%对4.1%；p≤0.05）。与安慰剂相比，CZP组患者报告身体功能有所改善（健康评估问卷残疾指数自基线的平均变化：CZP组为-0.25，安慰剂组为-0.03；p≤0.01）。在停用CZP或安慰剂后的期间，仅17例既往CZP组患者中的3例和6例既往安慰剂组患者中的2例在第52周时维持CDAI缓解，但重新使用CZP后病情再次改善。CZP组和安慰剂组的不良事件和严重不良事件发生率相当。