| Background and objective: Ulcerative colitis(UC)is a non-specific intestinal inflammatory disease whose etiology and pathogenesis have not been well defined.Traditional treatments include oral administration of aminosalicylic acid,glucocorticoids and immunosuppressive agents,but inefficacy,hormone-dependency and some serious complications have been found in the patients with these traditional treatments,thus there are many limits for the use of drugs.Recent years,many studies have shown that intestinal microbiota dysbiosis plays an important role in the development of UC.Fecal microbiota transplantation(FMT)refers to the transplantation of intestinal microbiota from a healthy individual into the gut of patients.As a special "organ transplant",FMT has been confirmed effective in the treatment of C.Difficile.Infection(CDI).Domestic and international clinical studies have reported the efficacy of FMT in inflammatory bowel disease,refractory constipation,metabolic syndrome and other diseases,while some clinical studies found no difference between FMT and placebo in the treatment of UC.The current security of FMT in UC is not very clear.This study aimed to observe the efficacy and safety of FMT in the treatment of active UC compared with traditional drug therapy through clinical trial studies.Methods: Our target population is patients with active ulcerative colitis.According to the patients' wishes,they were divided into 4 groups: treatment with aminosalicylic acid(group A),treatment with aminosalicylic acid,glucocorticoids and/or immunosuppressive agents(group B),aminosalicylic drugs and FMT group(FMT1 group),aminosalicylic acid drug,glucocorticoids and/or immunosuppressive agents and FMT group(FMT2 group).From September 2015 to March 2019,we screened 4 healthy volunteers as donors and recruited 98 patients with mild to moderate UC(Mayo score 4-10 points)at the Gastroenterology Department of Shanghai General Hospital to enter the traditional treatment group A.After 12 weeks of treatment,the patients who did not achieve remission were assigned to the three treatment groups according to their wishes: traditional treatment group B,FMT1 group,and FMT2 group.During the first month after treatment,we followed the patients' clinical symptoms,blood routine,inflammation indicators and adverse reactions per week.From 1 month to 3 months after treatment,we followed the patients' clinical symptoms,blood routine,biochemistry,inflammation indicators,colonoscopy and adverse reactions per month.We conducted the final follow-up at 12 th weeks.The primary outcome was a composite of clinical remission and endoscopic remission or response,which we defined as a total Mayo score of 2 or less,with all Mayo subscores of 1 or less,and at least a 1 point reduction from baseline in the endoscopy subscore.Secondary outcomes were: clinical remission(defined as combined Mayo subscores of 1 or less for rectal bleeding plus stool frequency);clinical response(defined as either a decrease of 3 points or more on the Mayo score,a 50% or greater reduction from baseline in combined rectal bleeding plus stool frequency Mayo subscores,or both);endoscopic response(defined as a Mayo endoscopy subscore of 1 or less,with a reduction of at least 1 point from baseline);endoscopic remission(defined as a Mayo endoscopy subscore of 0);histological remission(defined as the intestinal mucosal histopathological Nancy score of grade 1 or less).Results: In the group A,47 of 98 patients(47/98,48%)achieved the primary endpoint,47 of 98 patients(47/98,48%)achieved clinical remission,and 58 of 98 patients(58/98,59.2%)achieved clinical response,20 of 98 patients(20/98,20.4%)achieved endoscopic remission,52 of 98 patients(52/98,53.1%)achieved endoscopic response,and 22 of 98 patients(22/98,22.4%)achieved histological remission.In the group B,3 of 16 patients(3/16,18.8%)achieved the primary endpoint,3 of 16 patients(3/16,18.8%)achieved clinical remission,and 9 of 16 patients(9/16,56.3%)achieved clinical response,1 of 16 patients(1/16,6.3%)achieved endoscopic remission,6 of 16 patients(6/16,37.5%)achieved endoscopic response and 4 of 16 patients(4/16,25%)achieved histological remission.Among the FMT1 group,16 of 22 patients(16/22,72.7%)achieved the primary end point,17 of 22 patients(17/22,77.3%)achieved clinical remission,and 19 of 22 patients(19/22,86.4%)achieved clinical response,14 of 22 patients(14/22,63.6%)achieved endoscopic remission,19 of 22 patients(19/22,86.4%)achieved endoscopic response,12 of 22 patients(12/22,54.5%)achieved histological remission.In the FMT2 group,5 of 7 patients(5/7,71.4%)achieved the primary endpoint,5 of 7 patients(5/7,71.4%)achieved clinical remission,6 of 7 patients(6/7,85.7%)achieved clinical response,3 of 7 patients(3/7,42.9%)achieved endoscopic remission,6 of 7 patients(6/7,85.7%)achieved endoscopic response,and 6 of 7 patients(6/7,85.7%)achieved histological remission.The FMT1 group achieved the primary end point(p=0.003),clinical remission(p=0.001),endoscopic remission(p=0.001),and endoscopic response rate(p=0.004),which were significantly higher than those of the group B.The clinical response and histological remission rate in the FMT1 group were higher than those of the group B without statistical difference.The FMT2 group achieved more primary end point(p=0.026),clinical remission(p=0.026),histological remission(p=0.019)than those of the group B.The FMT2 group achieved more clinical response,endoscopic remission,endoscopy response than those of the group B but there was no statistical difference.Patients receiving FMT from donor c reached more primary outcome(p=0.048)and clinical remission(p=0.048)than those who receiving FMT from donor d.Patients receiving FMT from donor a achieved more clinical remission(p=0.032)and clinical response(p=0.035)than those in FMT receiving FMT from donor d.Patients' serum TNF-? level decreased after FMT,and significant difference was found between unresolved group and remission group.10 of 16 patients(10/16,62.5%)in the group B,5 of 22 patients(5/22,22%)in the FMT1 group,and 2 of 7 patients(2/7,28.6%)in the FMT2 group had adverse events.The probability of adverse events in group B was significantly higher than that of the FMT1 group(p=0.020).The incidence of adverse events was lower in the FMT2 group than in the group B(p=0.143).There was no significant difference in the incidence of adverse events between the FMT1 and FMT2 groups(p=1.000).Conclusions: 1.Aminosalicylic acid plus FMT treatment induced significantly higher UC remission rate and lower adverse events than those of the aminosalicylic drugs plus glucocorticoids and / or immunosuppressive therapy.2.Aminosalicylic acid plus glucocorticoids and / or immunosuppressive plus FMT treatment induced significantly higher UC remission rate than that of the aminosalicylic drugs plus glucocorticoids and / or immunosuppressive therapy.3.Different donors may affect the efficacy of FMT in the treatment of UC.4.Changes in serum TNF-? have relationship with the efficacy of FMT in the treatment of UC. |
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