Long-Term Safety And Efficacy Of Fecal Microbiota Transplantation In Active Ulcerative Colitis

Background and Aims:Increasing evidences have shown that fecal microbiota transplantation(FMT)could be an alternative therapeutic option for ulcerative colitis(UC).However,the efficacy and safety reports by different research centers varied and the reports on the long-term safety of FMT were very limited.This study aims to evaluate the efficacy and long-term safety of step-up FMT in UCMethods:Two clinical trials(NCT01790061,NCT02560727)for moderate-to-severe UC(Mayo score range 6-12)were performed from November 2012 to July 2017.Both studies were pooled for analysis on the safety and efficacy of FMT in UC over a one-year follow-up.The step-up FMT strategy included step 1:single FMT;step 2:multiple FMTs;and step 3:FMT/FMTs followed by immunosuppressants.Manual preparation of fecal microbiota was used before April 2014;washed microbiota transplantation(WMT)was used after April 2014Results:1.One hundred and nine patients were included for analysis.The average duration of UC was 6.5 years.The follow-up period ranged from 12 to 68 months.Two-hundred and forty-seven FMT procedures were performed in 109 patients;12.6%(31/247)of procedures were manual FMT and 87.4%(216/247)were WMT.66.0%(163/247)of FMTs were delivered through mid-gut and 34.0%(84/247)were delivered through colonic transendoscopic enteral tubing(TET)2.FMT-related AEs were observed in 17.4%(43/247)of FMT procedures including one serious AE(myasthenia gravis)and 56 non-serious AEs.82.5%(47/57),12.3%(7/57),and 5.3%(3/57)of AEs were graded as mild,moderate and severe,respectively All of AEs occurred within one month after FMT.Multivariable logistic regression analysis showed that both WMT and the delivery way of colonic TET were associated with a lower rate of FMT-related AEs(p=0.023,p=0.017,respectively)3.During the first course of step-up FMT,100.0%(109/109),29.4%(32/109)and 20.2%(22/109)of patients underwent step 1,step 2,and step 3,respectively.73.4%(80/109),75.2%(82/109),51.4%(56/109)and 28.4%(31/109)of patients achieved clinical response at one week,one month,three months,and six months after step-up FMT,respectively4.Ninety patients were included in the assessment of quality-of-life.The EQ-5D index score increased significantly in responders at one year after step-up FMT(p<0.0001)Conclusions:FMT should be a safe and effective treatment for UC.The improved fecal microbiota preparation and colonic TET might reduce the rate of AEs in UC.