The Long Term Safety Of Fecal Microbiota Transplantation For Crohn’s Disease

Objective: Fecal microbiota transplantation(FMT)has been used as a potential treatment option for Crohn’s disease(CD).However,there is still lack of safety evidence based on large samples of CD undergoing FMT.This study was designed to analyze adverse events(AE)and the risk factors in the treatment of CD with FMT.Methods: Active CD patients admitted to the Second Affiliated Hospital of Nanjing Medical University from October 2012 to December 2016 were enrolled.FMT via mid-gut for CD was performed.All patients were followed for at least 6 months.All AEs were described using Common Terminology Criteria for Adverse Events(CTCAE)Version 4.0.The severity of AE and its relevance to FMT were evaluated.We analyzed the possible risk factors of AE and the relationship between AE and the efficacy of FMT.Results: A total of 184 frequencies of FMT were performed in 139 patients with CD.During 1 month after FMT,25 AEs occurred,accounting for 13.6%(25/184).The AEs included increased frequency of defecation,fever,abdominal pain,flatulence,hematochezia,vomiturition,bloating and herpes zoster.84.0%(21/25)of the AEs were mild and self-limiting.Only 4 patients required medication.One patient developed persistent fever after FMT,and gradually improved after oral prednisone treatment.One patient developed hematochezia after FMT but it disappeared after FMT once again.One patient was discharged from hospital due to increased frequency of defecation after FMT,and the symptoms improved after steroid therapy.Herpes zoster appeared in one case and healed after symptomatic treatment.No serious AE occurred during the long-term follow-up.Among the possible risk factors of AE,only the preparation method of fecal microbiota was related to the occurrence of AE(P=0.012).Both the donor source(kinship or non-kinship)and fecal microbiota status(fresh or frozen)were not related to AE(P> 0.05).The incidence of AE in the manual preparation group was 21.7%(15/69),which was significantly higher than 8.7%(10/115)of the automated machine(GenFMTer)preparation group.It was further found that the FMT response rate of the manual preparation group was 77.6%(52/67)and the clinical remission rate was 58.2%(39/67).The FMT response rate of the GenFMTer group was 65.3%(47/72)and the clinical remission rate was 55.6%(40/72).Statistical analysis showed that there was no significant difference in FMT response rate and clinical remission rate between the two groups of fecal preparation methods(P>0.05).However,the clinical response rate and response rate in patients with AE were 45%(9/20)and 20%(4/20),respectively,which was significantly lower than 75.6%(90/119)and 63.0%(75/119)in patients without AE.The difference was statistically significant(P < 0.05).Conclusion: This cohort study based on the largest size of CD cases demonstrated that the incidence of AE after FMT was low,mostly mild and self-limiting.The fecal microbiota preparation by automated machine(Gen FMTer)reduced the rates of AEs,but did not affect the clinical efficacy in patients with CD.