Addition of an Immunomodulator to Infliximab Therapy Eliminates Antidrug Antibodies in Serum and Restores Clinical Response of Patients With Inflammatory Bowel Disease
Addition of an Immunomodulator to Infliximab Therapy Eliminates Antidrug Antibodies in Serum and Restores Clinical Response of Patients With Inflammatory Bowel Disease
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DOI：
10.1016/j.cgh.2012.10.020
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发表时间：
2013-04-01
影响因子：
12.6
通讯作者：
Chowers, Yehuda
中科院分区：
文献类型：
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作者：
Ben-Horin, Shomron;Waterman, Matti;Chowers, Yehuda
炎症性肠病患者对英夫利昔单抗失去反应，因为他们产生了针对该药物的抗体，因此很少有治疗选择。我们进行了回顾性分析，以调查5例对英夫利昔单抗（ATI）产生抗体的患者给予免疫调节剂是否恢复了对该药物的反应；3例患者给予硫唑嘌呤/6-巯基嘌呤，2例患者给予甲氨蝶呤。采用基于酶联免疫吸附法的竞争分析法，对患者给予免疫调剂前后采集的血清样本进行英夫利昔单抗和ATIs浓度及抗肿瘤坏死因子（TNF）活性分析。在所有患者中，ATIs水平逐渐下降，英夫利昔单抗的低谷水平升高；所有患者均恢复临床反应。在竞争试验中，免疫调节剂诱导的ATIs消除与血清中抗tnf活性的增加有关。在治疗中加入免疫调节剂可能有助于那些由于抗药物抗体的形成而对抗tnf药物失去反应的患者。
There are few therapeutic options for patients with inflammatory bowel disease who lose response to infliximab because they produced antibodies against the drug. We performed a retrospective analysis to investigate whether administration of immune modulators to 5 patients who developed antibodies to infliximab (ATI) restored response to this drug; 3 patients were given azathioprine/6-mercaptopurine and 2 patients were given methotrexate. Concentrations of infliximab and ATIs, and antitumor necrosis factor (TNF) activity, were analyzed using enzyme-linked immunosorbent assay-based competition assays of serum samples collected before and after patients were given the immunomodulator. In all patients, levels of ATIs gradually decreased and trough levels of infliximab increased; clinical responses were restored to all patients. In competition assays, immunomodulator-induced elimination of ATIs was associated with increased anti-TNF activity in serum. The addition of immunomodulators to therapy might be helpful to patients who have lost response to anti-TNF agents owing to formation of antidrug antibodies.