Shin Jongbeom, Baek Ga Hyeon, Cha Boram, Park Soo-Hyun, Lee Jung-Hwan, Kim Jun-Seob, Kwon Kye Sook
Department of Internal Medicine, Inha University College of Medicine, Incheon 22332, Republic of Korea.
Department of Nano-Bioengineering, Incheon National University, Incheon 22012, Republic of Korea.
Biomedicines. 2024 Apr 3;12(4):800. doi: 10.3390/biomedicines12040800.
In patients with ulcerative colitis (UC), the development of an antidrug antibody (ADA) to anti-tumor necrosis factor (TNF)α agent is a crucial problem which aggravates the clinical course of the disease, being cited as one of the most common causes for discontinuing anti-TNFα treatment. This is due to ADA eventually causing secondary LOR, leading to discontinuation of anti-TNFα treatment. Recently, research on the microbiome and relationship between worsening UC and dysbiosis has been conducted. Further, investigations on the association between the microbiome and secondary LOR are increasing. Here, we present the therapeutic effect of fecal microbiota transplantation (FMT) on a 42-year-old man with secondary LOR and high ADA levels. FMT has recently been used for the treatment of, and for overcoming, drug resistance through microbiome modification. Stool samples were collected from the patient before and 4 weeks after FMT. Symptoms, including hematochezia and Mayo endoscopy sub-scores, improved after FMT, while ADA levels decreased by one-third to less than half the value (29 ng/mL) compared to before FMT (79 ng/mL). Additionally, the trough level of infliximab became measurable, which reflects the improvement in the area under the concentration (AUC). , , , , , and , which regulate immune responses and alleviate inflammation, also increased after FMT. We report a case in which microbiome modification by FMT increased the AUC of anti-TNFα in a patient who developed secondary LOR during anti-TNFα treatment, thereby improving symptoms and mucosal inflammation.
在溃疡性结肠炎(UC)患者中,对抗肿瘤坏死因子(TNF)α药物产生抗药抗体(ADA)是一个关键问题,它会加重疾病的临床进程,被认为是停止抗TNFα治疗的最常见原因之一。这是因为ADA最终会导致继发性药物失效,从而导致抗TNFα治疗中断。最近,已经开展了关于微生物群以及UC病情恶化与生态失调之间关系的研究。此外,关于微生物群与继发性药物失效之间关联的调查也越来越多。在此,我们展示了粪便微生物群移植(FMT)对一名42岁继发性药物失效且ADA水平高的男性患者的治疗效果。FMT最近已被用于治疗以及通过改变微生物群来克服耐药性。在FMT前和FMT后4周采集患者的粪便样本。FMT后,包括便血和梅奥内镜亚评分在内的症状有所改善,而ADA水平降至FMT前(79 ng/mL)的三分之一至不到一半(29 ng/mL)。此外,英夫利昔单抗的谷浓度变得可测,这反映了浓度-时间曲线下面积(AUC)的改善。调节免疫反应和减轻炎症的 、 、 、 、 以及 ,在FMT后也有所增加。我们报告了一例在抗TNFα治疗期间出现继发性药物失效的患者,通过FMT改变微生物群增加了抗TNFα的AUC,从而改善了症状和黏膜炎症。