Li Qianqian, Ding Xiao, Liu Yujie, Marcella Cicilia, Dai Min, Zhang Ting, Bai Jianling, Xiang Liyuan, Wen Quan, Cui Bota, Zhang Faming
Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China.
Front Pharmacol. 2021 May 17;12:658087. doi: 10.3389/fphar.2021.658087. eCollection 2021.
How to handle patients with anti-tumor necrosis factor (anti-TNF) failure was a common challenge to clinicians in Crohn's disease (CD). The present study is dedicated to clarifying whether fecal microbiota transplantation (FMT) could be a switch therapy for patients with prior failure of infiiximab (IFX) in CD in a long-term observation. Thirty-six patients with CD who had prior failure of IFX were recruited from January 2013 to December 2019. The "one-hour FMT protocol" was followed in all patients. All patients received the first course of FMT through gastroscopy or mid-gut transendoscopic enteral tubing. After April 2014, the methodology of FMT was coined as washed microbiota transplantation (WMT), substituting for the manual methods, which is dependent on the automatic microbiota purification system and the washing process. The primary endpoint of this study was the clinical remission at one month and one year after FMT. The secondary endpoint was the safety of FMT in the short and long term, and clinical factors as predictors for long-term efficacy of FMT. Clinical factors as independent predictors of efficacy from FMT were isolated using univariable and multivariable logistic regression analysis. There was no significant difference in the rates of clinical response and remission between IFX treatment stage and FMT treatment stage (at one month, three months and six months after administration) ( > 0.05). Compared with those of 19 patients who achieved clinical remission at one month after FMT, the rates of clinical relapse were significantly higher in 18 patients who achieved clinical remission at one month after IFX [log-rank test = 0.0009 HR = 3.081 (95% CI 1.43-6.639)]. Multivariate analysis revealed that the gender of donor (95% CI: 0.001-0.72; = 0.031) was an independent predictor of efficacy at one year after FMT. No serious adverse events (AEs) associated with FMT were observed during and after FMT. The rate of AEs was significantly lower in group FMT than that in group IFX ( = 0.002). The present findings first time provided the evidence for clinicians to consider FMT into practice as an alternative switch therapy for patients with prior loss of response or intolerance to IFX in CD. https://clinicaltrials.gov, identifier NCT01793831.
如何处理抗肿瘤坏死因子（抗TNF）治疗失败的克罗恩病（CD）患者，是临床医生面临的一项常见挑战。本研究旨在通过长期观察，阐明粪便微生物群移植（FMT）是否可作为英夫利昔单抗（IFX）治疗失败的CD患者的转换疗法。2013年1月至2019年12月招募了36例IFX治疗失败的CD患者。所有患者均遵循“一小时FMT方案”。所有患者通过胃镜或中肠经内镜肠内导管接受第一疗程的FMT。2014年4月后，FMT方法被称为洗过的微生物群移植（WMT），取代了依赖自动微生物净化系统和清洗过程的手工方法。本研究的主要终点是FMT后1个月和1年的临床缓解。次要终点是FMT短期和长期的安全性，以及作为FMT长期疗效预测指标的临床因素。使用单变量和多变量逻辑回归分析分离出作为FMT疗效独立预测指标的临床因素。IFX治疗阶段和FMT治疗阶段（给药后1个月、3个月和6个月）的临床反应和缓解率无显著差异（>0.05）。与FMT后1个月达到临床缓解的19例患者相比，IFX后1个月达到临床缓解的18例患者的临床复发率显著更高[对数秩检验=0.0009，HR=3.081（95%CI 1.43-6.639）]。多变量分析显示，供体性别（95%CI：0.001-0.72；=0.031）是FMT后1年疗效的独立预测指标。FMT期间及之后未观察到与FMT相关的严重不良事件（AE）。FMT组的AE发生率显著低于IFX组（=0.002）。本研究结果首次为临床医生将FMT作为CD中先前对IFX无反应或不耐受患者的替代转换疗法应用于实践提供了证据。https://clinicaltrials.gov，标识符NCT01793831 。
