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联合使用疾病活动度和英夫利昔单抗血清谷浓度来早期预测类风湿关节炎患者对英夫利昔单抗的(无)反应。

The combined use of disease activity and infliximab serum trough concentrations for early prediction of (non-)response to infliximab in rheumatoid arthritis.

机构信息

Department of Pharmacy, Sint Maartenskliniek, Nijmegen, the Netherlands.

出版信息

Br J Clin Pharmacol. 2013 Dec;76(6):939-45. doi: 10.1111/bcp.12142.

Abstract

AIM

Early prediction of (non-)response to infliximab therapy can improve therapeutic benefit by avoiding unnecessary periods of high disease activity during ineffective therapy. This prospective cohort study therefore aimed to study the predictive value of (1) disease activity alone and (2) infliximab serum trough concentrations in addition to disease activity 6 weeks after start of treatment for achieving low disease activity after 6 months.

METHODS

Disease activity and infliximab serum trough concentrations were assessed in all rheumatoid arthritis (RA) patients at 2, 6 and 26 weeks after initiation of infliximab therapy. Receiver operating characteristic (ROC) curves and Youden indices were used to calculate specificity for prediction of good response after 6 months while aiming for maximum sensitivity.

RESULTS

Fifty-seven consecutive RA patients starting with infliximab therapy were included. After 6 months, 15 (26%, 95 % CI 15, 38%) patients reached good European League against Rheumatism (EULAR) response. A disease activity score <4.2 at 6 weeks after initiation of therapy was a moderate predictor for reaching EULAR response after 6 months (sensitivity 100%, specificity 49%). Infliximab serum trough concentrations (>2.5 mg l(-1)) as predictor complimentary to disease activity (<4.2) slightly increased the specificity from 49% to 54% without changing the sensitivity (100%). As 39% of the patients did not fulfill at least one of these criteria at week 6, these patients could already be switched to another therapy after 6 weeks.

CONCLUSIONS

The combination of disease activity and infliximab serum trough concentrations could be a fair predictor to identify early (after 6 weeks) patients who have insufficient response after 6 months of therapy.

摘要

目的

早期预测英夫利昔单抗治疗的反应(无反应或有反应)可以通过避免在无效治疗期间出现不必要的高疾病活动期,从而提高治疗效益。因此,本前瞻性队列研究旨在研究(1)疾病活动本身和(2)在治疗开始后 6 周时除疾病活动外还测定英夫利昔单抗血清谷浓度,对于治疗 6 个月后达到低疾病活动的预测价值。

方法

在英夫利昔单抗治疗开始后 2、6 和 26 周时,评估所有类风湿关节炎(RA)患者的疾病活动和英夫利昔单抗血清谷浓度。使用受试者工作特征(ROC)曲线和 Youden 指数来计算预测治疗 6 个月后达到良好缓解反应的特异性,同时追求最大敏感性。

结果

共纳入 57 例连续起始英夫利昔单抗治疗的 RA 患者。6 个月后,15 例(26%,95%CI 15%,38%)患者达到了良好的欧洲抗风湿病联盟(EULAR)缓解。治疗开始后 6 周时疾病活动评分<4.2 是达到 6 个月后 EULAR 缓解的中度预测指标(敏感性 100%,特异性 49%)。英夫利昔单抗血清谷浓度(>2.5mg/L)作为对疾病活动(<4.2)的补充预测指标,特异性从 49%略微提高到 54%,而敏感性(100%)保持不变。由于 39%的患者在第 6 周时至少不符合其中一项标准,这些患者在 6 周后即可转换为其他治疗。

结论

疾病活动和英夫利昔单抗血清谷浓度的组合可能是一种公平的预测指标,可以早期(6 周后)识别出治疗 6 个月后反应不足的患者。

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