The Efficacy And Safety Of Tacrolimus In The Treatment Of Refractory Ulcerative Colitis:A Meta- Analysis

Background:Ulcerative colitis(UC)is a type of inflammatory bowel disease.Its pathogenic mechanism is not yet clear.In addition to surgical bowel resection,there is no effective theraphy for cure.For such patients,the primary therapeutic goal pursued by clinicians is to induce and maintain clinical remission.The traditional therapeutic drugs of UC include aminosalicylic acid preparations,hormones,and purine drugs(azathioprine,6-mercaptopurine).Most patients can benefit from the above-mentioned drugs and maintain stability,but there are still some patients.After receiving the above-mentioned drug treatment,the treatment failed and the recurrence worsened.For this group of patients,we need to consider the choice of drugs for switch therapy.At present,our guidelines recommend that cyclosporine and infliximab should be used for switch therapy,both of which require intravenous administration,and patients often require hospitalization.Tacrolimus and cyclosporine have a similar pharmacological mechanism,but the immunosuppressive effect is higher than that of cyclosporine.Even in the presence of gastro-intestinal diseases,the absorption rate of tacrolimus in the gastrointestinal tract is still high,and it has the advantage of oral administration,which saves medical costs to some extent.In China,the clinical data of tacrolimus are mostly derived from transplant patients.The lack of experience in the use of drugs in patients with ulcerative colitis,coupled with less mention of this drug for ulcerative colitis from research reports or clinical guidelines,making the use of tacrolimus for ulcerative colitis has not been taken seriously.Objective: To determine the efficacy and safety of tacrolimus in the treatment of refractory ulcerative colitis;To evaluate the difference of tacrolimus and cyclosporine/biologics in the treatment of refractory ulcerative colitis.METHODS: We searched four electronic databases(Cochrane Library,Pub Med,Ovid-Medline,and Embase).Search terms includes "tacrolimus,FK506,inflammatory bowel disease,ulcerative colitis,treatment,and therapy".The search deadline was December 2017.The analysis were performed on the included literature for extracted data.The statistical analysis in the research process was performed using Rev Man 5.3 software and Stata 11.0 software.Results: A total of 2224 articles were retrieved,12 of which were included for meta-analysis.Efficacy analysis results(effective events/sample size):1 TAC group(37/72)had a better clinical response than placebo group(6/50)in the treatment of refractory ulcerative colitis(p=0.0003);2.1 There was no significant difference in clinical response?clinical remission between TAC group(73/121,166/283)and anti-TNF? group(IFX)(88/137,166/269)in the treatment of refractory ulcerative colitis(p=0.1,p=0.46);2.2 There was no significant difference in clinical remission between TAC group(33/46)and anti-TNF? group(ADA)(20/28)in the treatment of refractory ulcerative colitis(p=0.98);2.3 There was no significant difference in clinical response?clinical remission between TAC group(31/50,20/50)and anti-TNF? group(IFX+ADA)(32/50,14/50)in the treatment of refractory ulcerative colitis(p=0.84?p=0.21);3 There was no significant difference in clinical response ? clinical remission between TAC group(29/57,79/133)and Cs A group(64/99,145/254)of refractory ulcerative colitis(p=0.91,p=0.58).Safety analysis results(adverse events/sample size):1 TAC group(34/72)had a worse safety than placebo group(13/50)in the treatment of refractory ulcerative colitis(p=0.01);2.1 TAC group(40/130)had a worse safety than anti-TNF? group(IFX)(24/132)in the treatment of refractory ulcerative colitis(p=0.01);2.2 There was no significant difference in safety between TAC group(6/50)and anti-TNF ? group(IFX+ADA)(8/50)in the treatment of refractory ulcerative colitis(p=0.57);3 There was no significant difference in safety between TAC group(6/54)and Cs A group(10/82)in the treatment of refractory ulcerative colitis(p=0.56).Conclusion: Tacrolimus is effective in the treatment of refractory ulcerative colitis.Although adverse events(such as tremors and abnormal renal function)occur during treatment,it does not cause irreversible damage or death,and most adverse events can be solved by adjusting drug dosage or withdrawal.In addition,we found that the efficacy of tacrolimus in refractory ulcerative colitis is similar to that of anti-TNF agents/cyclosporine,and there is no statistical difference between them.The safety of tacrolimus is inferior to infliximab,but there was no statistical difference between tacrolimus and cyclosporine.