Risk of Tuberculosis Reactivation With Tofacitinib (CP-690550)

Risk of Tuberculosis Reactivation With Tofacitinib (CP-690550)
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DOI:
10.1093/infdis/jis269
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发表时间:
2012-06-01
影响因子:
6.4
通讯作者:
Bishai, William R.
Bishai, William R.
中科院分区:
医学2区
文献类型:
--
作者:
Maiga, Mamoudou;Lun, Shichun;Bishai, William R.

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潜伏性结核感染(LTBI)的个体存在再激活的风险,并且慢性炎症性疾病的几种治疗与这种再激活高度相关。一种新的Janus激酶抑制剂,托法替尼(CP-690550),已显示出治疗炎症性疾病的有希望的结果,从而提高了对活动性结核病风险的关注。我们的目标是使用小鼠结核病模型来表征托法替尼对LTBI的影响。我们的数据表明,托法替尼减少结核分枝杆菌的宿主遏制,促进肺部细菌复制,表明结核病复发。托法替尼可能对人体中LTBI再激活具有显著风险。
Individuals with latent tuberculosis infection (LTBI) live with a risk of reactivation, and several treatments for chronic inflammatory conditions are highly associated with such reactivation. A new Janus kinase inhibitor, tofacitinib (CP-690550), has shown promising results for treatment of inflammatory disorders, thus raising concerns of risk of active tuberculosis. Our goal was to characterize the impact of tofacitinib on LTBI using a mouse model of contained tuberculosis. Our data indicate that tofacitinib reduces host containment of Mycobacterium tuberculosis and promotes bacterial replication in the lungs, suggesting tuberculosis reactivation. Tofacitinib may carry a significant risk for LTBI reactivation in humans.