Einarson Thomas R, Bereza Basil G, Ying Lee Xin, Lelli Filippo
a Leslie Dan Faculty of Pharmacy , University of Toronto , Toronto , ON , Canada.
b Janssen-Cliag A/S , Birkerød , Denmark.
Curr Med Res Opin. 2017 Aug;33(8):1433-1449. doi: 10.1080/03007995.2017.1335001. Epub 2017 Jun 11.
Biologics used to treat Crohn's disease (CD) may lose their effect over time, requiring dose escalation. Little information is available on this topic.
To summarize rates of dose escalation, duration, de-escalation in observational studies of CD in adults treated with adalimumab, infliximab, and vedolizumab in Europe.
Two independent investigators searched Medline and Embase for observational studies published in 1998-2015 and proceedings from four major scientific meetings. Rates were summarized descriptively.
In total, 58 articles from 12 European countries were analyzed (49 full articles, nine abstracts), providing 65 reports with 7,850 patients; 35 reported on 3,830 patients with adalimumab (ADA), and 30 on 4,020 patients with infliximab (IFX). Overall, 29.9% ± 3.5% of patients required dose escalation; 32.8% ± 6.2% with ADA and 25.2% ± 2.4% with IFX (p = .35 between drugs). Rates increased according to line of treatment: 19% for first line, 37% second, and 41% third. The median time to loss of response was 12 months, and the weighted average was 15.1 ± 5.9 months. Median time to escalation was 6.7 months; 6.7 months for ADA and 7.5 for IFX (p = .86). Short-term response rates to escalation were 63% for ADA and 45% for IFX (p = .08). There were no papers available for vedolizumab.
A substantial proportion of patients receiving ADA or IFX for Crohn's disease require dose escalation after a short period of time.
用于治疗克罗恩病（CD）的生物制剂可能会随着时间推移失去疗效，需要增加剂量。关于这一主题的信息很少。
总结欧洲接受阿达木单抗、英夫利昔单抗和维多珠单抗治疗的成年CD患者观察性研究中的剂量增加率、持续时间及剂量降低情况。
两名独立研究人员检索了1998年至2015年发表在Medline和Embase上的观察性研究以及四大科学会议的会议记录。对发生率进行描述性总结。
共分析了来自12个欧洲国家的58篇文章（49篇全文，9篇摘要），提供了65份报告，涉及7850例患者；35篇报告了3830例接受阿达木单抗（ADA）治疗的患者，30篇报告了4020例接受英夫利昔单抗（IFX）治疗的患者。总体而言，29.9%±3.5%的患者需要增加剂量；ADA组为32.8%±6.2%，IFX组为25.2%±2.4%（两种药物之间p=0.35）。剂量增加率根据治疗线数而增加：一线为19%，二线为37%，三线为41%。失去反应的中位时间为12个月，加权平均值为15.1±5.9个月。增加剂量的中位时间为6.7个月；ADA为6.7个月，IFX为7.5个月（p=0.86）。ADA增加剂量后的短期反应率为63%，IFX为45%（p=0.08）。没有关于维多珠单抗的可用论文。
相当一部分接受ADA或IFX治疗克罗恩病的患者在短时间后需要增加剂量。
