AP&T: 炎症性肠病患者对抗TNFα药物反应的丧失取决于治疗持续时间

2021-10-26 MedSci原创 MedSci原创

抗肿瘤坏死因子α(抗TNFα)药物被广泛用作炎症性肠病(IBD)患者的维持治疗。成功诱导缓解后,但是仍然有高达13%-21%的患者会对抗TNFα失去治疗反应。

1992年,首例患有严重克罗恩病 (CD)的患者在荷兰阿姆斯特丹的医学中心(AMC)接受了抗肿瘤坏死因子(TNF)抗体治疗,临床反应迅速且非常显著,由此胃肠病学杂志宣称,1BD的新纪元由此开启。然而,在临床实践中,仍然有很大比例的患者对于抗TNFα治疗具有不佳的临床反应,虽然在开始抗TNFα后立即治疗失败的年度风险相对较高,但随着治疗持续时间的延长,无应答的风险可能会降低。本项研究的主要目的是评估炎症性肠病患者的反应丧失的发生率是否随着治疗持续时间的延长而下降。次要目的是确定反应丧失的预测因素,并确定总体停药和抗TNFα剂量强化的时间依赖性风险。

 

这是一项针对溃疡性结肠炎 (UC) 或克罗恩病 (CD) 患者的多中心、回顾性队列研究,这些患者在 2011 年至 2019 年期间接受抗 TNFα治疗至少 4 个月。原发性无反应定义为在抗 TNFα治疗开始后 4 个月内因疾病活动而停用抗TNFα治疗。反应丧失定义为治疗四个月后因疾病活动而停用抗TNFα。研究人员采用生存时间进行建模。通过 Cox 回归分析确定反应丧失的预测因子。次要结果包括总体抗 TNFα 停用和剂量递增的关系。

 

研究最后总共纳入了 708 名炎症性肠病患者,所有患者总共接受了844次抗TNFα治疗。其中211次 (25.0%) 发生治疗应答丧失,66次 (31.3%) 检测到抗药物抗体。在第一年,反应丧失的发生率是治疗四年后的三倍(17.2% VS 4.8%,P< 0.001)。停用抗TNFα的发生率(28.6% VS 14.0%,P< 0.001)和剂量递增(38.0% VS 6.8%,P < 0.001) 也分别从在四年后显着下降。反应丧失的预测因素包括 UC(相对于 CD, [aHR] 1.53,95% CI 1.10-2.15),以及在 CD 患者中,狭窄或穿透性疾病(aHR 1.68,95% CI 1.15-2.46)和男性性别(aHR 0.55,95% CI 0.38-0.78)是抗TNF-α治疗失败的危险因素。免疫调节剂对抗药物抗体的反应丧失具有保护作用(aHR 0.42,95% CI 0.24-0.74)。

 

 随着时间的推移,抗TNFα停用、抗TNFα因副作用的发生而停用和剂量增加的发生率显着下降。

原始出处:

Johannes P. D. et al. Loss of response to anti-TNFα agents depends on treatment duration in patients with inflammatory bowel disease. Alimentary Pharmacology & Therapeutics.2021.

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    2021-11-07 gongliu
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    2022-01-29 mfx808
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  4. [GetPortalCommentsPageByObjectIdResponse(id=1995767, encodeId=490c1995e673d, content=<a href='/topic/show?id=ba231e5989a' target=_blank style='color:#2F92EE;'>#TNFα#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17598, encryptionId=ba231e5989a, topicName=TNFα)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=1a5a149, createdName=gongliu, createdTime=Sun Nov 07 15:18:06 CST 2021, time=2021-11-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1670808, encodeId=21ed16e080811, content=<a href='/topic/show?id=abd35513ed5' target=_blank style='color:#2F92EE;'>#抗TNF#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=55137, encryptionId=abd35513ed5, topicName=抗TNF)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=7dc326754916, createdName=mfx808, createdTime=Sat Jan 29 02:18:06 CST 2022, time=2022-01-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1952893, encodeId=8e341952893c7, content=<a href='/topic/show?id=49ff8e70301' target=_blank style='color:#2F92EE;'>#药物反应#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=87703, encryptionId=49ff8e70301, topicName=药物反应)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=da20314, createdName=lfcmxl, createdTime=Thu Jun 30 06:18:06 CST 2022, time=2022-06-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1066441, encodeId=b7621066441d5, content=非常感谢,非常好的内容,学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=51, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2020/02/15/7274ed1be4747d648e4e2f7f62fae403.jpg, createdBy=d8d65273314, createdName=1482963am12暂无昵称, createdTime=Wed Nov 03 00:26:37 CST 2021, time=2021-11-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1401802, encodeId=5c2014018028e, content=<a href='/topic/show?id=17e21e57943' target=_blank style='color:#2F92EE;'>#TNF#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=51, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17579, encryptionId=17e21e57943, topicName=TNF)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83eqjVbfRD4f4vibEcZVcvato8Qib1gGtZJiayXCMFgHrkeErSiaxdYMiabKGxY2an9muxWCkUJbjFPViaC6A/132, createdBy=e4fb2361580, createdName=snowpeakxu, createdTime=Thu Oct 28 14:18:06 CST 2021, time=2021-10-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1503690, encodeId=0af01503690db, content=<a href='/topic/show?id=4f215634296' target=_blank style='color:#2F92EE;'>#持续时间#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=56342, encryptionId=4f215634296, topicName=持续时间)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=13e29684821, createdName=zhwj, createdTime=Thu Oct 28 14:18:06 CST 2021, time=2021-10-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1547489, encodeId=6607154e489ed, content=<a href='/topic/show?id=4ef26e01766' target=_blank style='color:#2F92EE;'>#炎症性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=67017, encryptionId=4ef26e01766, topicName=炎症性)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=09e813968720, createdName=12498dd9m15暂无昵称, createdTime=Thu Oct 28 14:18:06 CST 2021, time=2021-10-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1600119, encodeId=982c1600119b1, content=<a href='/topic/show?id=508e6e03203' target=_blank style='color:#2F92EE;'>#炎症性肠病患者#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=67032, encryptionId=508e6e03203, topicName=炎症性肠病患者)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a9fa18776644, createdName=huangshifeng, createdTime=Thu Oct 28 14:18:06 CST 2021, time=2021-10-28, status=1, ipAttribution=)]
    2021-11-03 1482963am12暂无昵称

    非常感谢,非常好的内容,学习了

    0

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    2021-10-28 snowpeakxu
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    2021-10-28 zhwj
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