Objective:To assess the short-term efficacy and safety of tacrolimus in patients with refractory Crohn′s disease (CD) , and analyze the influencing factors of clinical response.Methods:A single center restrospective cohort study was conducted. The clinical data of patients with refractory CD in Renji Hospital of Shanghai Jiaotong University School of Medicine from March 2014 to June 2019 were analyzed retrospectively. The patients received tacrolimus treatment for at least 3 months. Clinical response, clinical remission and relapse after tacrolimus treatment were evaluated by Crohn′s disease activity index (CDAI) . According to the existence of clinical response after 3 months of tacrolimus treatment, the patients were divided into clinical response group and non-clinical response group. The differences in clinical data between the 2 groups were assessed by univariate analysis. The variables with P<0.1 in univariate analysis and having clinical significance were further analyzed by multivariate Logistic regression to determine the independent risk factors of clinical response. The receiver operating characteristic (ROC) curve analysis was performed to evaluate the value of risk factors in predicting the clinical response of tacrolimus for the treatment of refractory CD. Results:A total of 45 patients with refractory CD were included, including 31 males and 14 females with the age of 32 (27, 39) years old. The disease duration was 61.0 (28.0, 97.5) months. The CDAI was 203 (175, 229) points before the treatment of tacrolimus while it decreased to 137 (117, 175) points after the treatment of tacrolimus for 3 months, and the difference was significant ( Z = -5.512, P<0.01) . After the treatment of tacrolimus for 3 months, 13 patients (28.9%) with clinical response were set as clinical response group and 32 (71.1%) without clinical response were set as non-clinical response group. Univariate analysis showed that the differences in gender, CDAI before the treatment of tacrolimus and neutrophil-to-lymphocyte ratio (NLR) between the clinical response group and non-clinical response group were statistically significant (all P<0.05) . Gender, CDAI before the treatment of tacrolimus and NLR were included for the multivariate Logistic regression analysis. The results showed that CDAI ( OR = 1.026, 95% CI: 1.006-1.046, P = 0.012) and NLR ( OR = 2.605, 95% CI: 1.290-5.258, P = 0.008) were the independent risk factors for predicting clinical response. The areas under ROC curve of CDAI, NLR and NLR combined with CDAI in predicting clinical response of tacrolimus in patients with refractory CD were 0.786 (95% CI : 0.648-0.924) , 0.764 (95% CI: 0.595-0.934) and 0.861 (95% CI : 0.729-0.992) , the optimal cut-off values were 189.15, 2.82 and 0.31, sensitivities were 100%, 84.6% and 84.6%, and specificities were 53.1%, 71.9% and 84.4%, respectively. Twenty-six patients continued to receive tacrolimus for 12 months, and the clinical remission rate was 73.1% (19/26) and the recurrence rate was 26.9% (7/26) . Forty-five patients were followed up for 1 year, adverse effects occurred in 6 and there was no severe adverse effects during the treatment of tacrolimus. Conclusions:Tacrolimus can be used as an immunosuppressant to induce the remission and maintenance in refractory CD patients. CDAI and NLR can be used as independent indicators to predict the clinical response of tacrolimus in the treatment of patients with refractory CD, and the combination of CDAI and NLR has higher prediction efficiency.

Objective:To assess the short-term efficacy and safety of tacrolimus in patients with refractory Crohn′s disease (CD) , and analyze the influencing factors of clinical response.Methods:A single center restrospective cohort study was conducted. The clinical data of patients with refractory CD in Renji Hospital of Shanghai Jiaotong University School of Medicine from March 2014 to June 2019 were analyzed retrospectively. The patients received tacrolimus treatment for at least 3 months. Clinical response, clinical remission and relapse after tacrolimus treatment were evaluated by Crohn′s disease activity index (CDAI) . According to the existence of clinical response after 3 months of tacrolimus treatment, the patients were divided into clinical response group and non-clinical response group. The differences in clinical data between the 2 groups were assessed by univariate analysis. The variables with P<0.1 in univariate analysis and having clinical significance were further analyzed by multivariate Logistic regression to determine the independent risk factors of clinical response. The receiver operating characteristic (ROC) curve analysis was performed to evaluate the value of risk factors in predicting the clinical response of tacrolimus for the treatment of refractory CD. Results:A total of 45 patients with refractory CD were included, including 31 males and 14 females with the age of 32 (27, 39) years old. The disease duration was 61.0 (28.0, 97.5) months. The CDAI was 203 (175, 229) points before the treatment of tacrolimus while it decreased to 137 (117, 175) points after the treatment of tacrolimus for 3 months, and the difference was significant ( Z = -5.512, P<0.01) . After the treatment of tacrolimus for 3 months, 13 patients (28.9%) with clinical response were set as clinical response group and 32 (71.1%) without clinical response were set as non-clinical response group. Univariate analysis showed that the differences in gender, CDAI before the treatment of tacrolimus and neutrophil-to-lymphocyte ratio (NLR) between the clinical response group and non-clinical response group were statistically significant (all P<0.05) . Gender, CDAI before the treatment of tacrolimus and NLR were included for the multivariate Logistic regression analysis. The results showed that CDAI ( OR = 1.026, 95% CI: 1.006-1.046, P = 0.012) and NLR ( OR = 2.605, 95% CI: 1.290-5.258, P = 0.008) were the independent risk factors for predicting clinical response. The areas under ROC curve of CDAI, NLR and NLR combined with CDAI in predicting clinical response of tacrolimus in patients with refractory CD were 0.786 (95% CI : 0.648-0.924) , 0.764 (95% CI: 0.595-0.934) and 0.861 (95% CI : 0.729-0.992) , the optimal cut-off values were 189.15, 2.82 and 0.31, sensitivities were 100%, 84.6% and 84.6%, and specificities were 53.1%, 71.9% and 84.4%, respectively. Twenty-six patients continued to receive tacrolimus for 12 months, and the clinical remission rate was 73.1% (19/26) and the recurrence rate was 26.9% (7/26) . Forty-five patients were followed up for 1 year, adverse effects occurred in 6 and there was no severe adverse effects during the treatment of tacrolimus. Conclusions:Tacrolimus can be used as an immunosuppressant to induce the remission and maintenance in refractory CD patients. CDAI and NLR can be used as independent indicators to predict the clinical response of tacrolimus in the treatment of patients with refractory CD, and the combination of CDAI and NLR has higher prediction efficiency.

Background: Some of the active perianal fistulizing Crohn's disease (CD) patients achieving remission with infliximab (IFX) therapy would develop relapse of perianal fistula within weeks to years after discontinuation of IFX therapy. Aims: To assess the outcomes of patients with perianal fistulizing CD after discontinuation of IFX therapy and the risk factors for relapse of perianal fistula. Methods: The clinical data of patients with perianal fistulizing CD who received IFX therapy at Shanghai Renji Hospital between June 2013 and May 2019 and stopped IFX therapy after achieving complete or partial radiological remission were collected retrospectively and analyzed. Demographic data, clinical and imaging characteristics, as well as data of IFX treatment and relapse of perianal fistula were extracted. Kaplan-Meier analysis was performed to calculate the cumulative probabilities of perianal and luminal relapse, while Cox proportional hazards model was applied to identify the risk factors for relapse. Results: A total of 56 perianal fistulizing CD patients who had been treated with IFX and stopped IFX therapy were included. Of them 26 achieved complete radiological remission and 30 achieved partial radiological remission. The median follow-up time was 20.5 months. Twenty-one patients (37.5%) had relapse of perianal fistula. The cumulative probabilities of perianal relapse were 29.0%, 33.7% and 42.8% at 12, 24 and 60 months after IFX discontinuation, respectively; and the cumulative probabilities of luminal relapse were 21.7%, 31.2% and 56.4% at 12, 24 and 60 months after IFX discontinuation, respectively. Multivariate analysis showed that non-stricturing and non-penetrating type (HR=9.711, 95% CI: 1.210-77.939, P=0.032) and involvement of rectum (HR=3.034, 95% CI: 1.119-8.231, P=0.029) were independent risk factors for relapse of perianal fistula, while the frequency of using of IFX therapy was a protective factor (HR=0.885, 95% CI: 0.792-0.990, P=0.032). Conclusions: There is a high risk of relapse of perianal fistulizing CD after discontinuation of IFX therapy. Non-stricturing and non-penetrating type and rectal involvement are risk factors for relapse of perianal fistula, and increasing the frequencies of using IFX therapy is crucial for the maintenance of remission.

Background:Reactivation of hepatitis B virus (HBV)in the context of immunosuppressive therapy is serious. Biological agents are known having the effect to increase the risk of HBV reactivation in patients with inflammatory bowel disease (IBD)who are seropositive for HBsAg and/ or HBcAb. Aims:To study the HBV reactivation in IBD patients with HBV infection who are treated with infliximab (IFX)in China. Methods:A retrospective study was conducted between March 2014 and March 2017 in Shanghai Renji Hospital. Consecutive IBD patients who were seropositive for HBcAb and treated with IFX were enrolled. The clinical and follow-up data were analyzed and the changes in viral replication and liver function were recorded. Results:Of the 194 IBD patients treated with IFX,28 had active or prior HBV infection. The overall prevalence of HBV infection was 14. 4%,and that of active infection was 4. 6% . The mean number of IFX treatment course was 6. 96 ± 3. 47,and the mean follow-up period was (15. 32 ± 10. 47)months. Fifteen patients (53. 6%)received prophylactic antiviral treatment,one with lamivudine and 14 with entecavir. Ten patients (35. 7%) received synergistic treatment with immunosuppressants,of which,one (10. 0%)with active HVB infection (HBsAg positive and HBV-DNA negative)suffered HBV reactivation. In this reactivation case,lamivudine antiviral prophylaxis was used initially and the reactivation was resolved when entecavir was used instead of lamivudine. Conclusions:IBD patients receiving IFX treatment should be screened for HBV infection. In patients who are seropositive for HBsAg and/ or HBcAb, prophylactic antiviral agents with low resistance rate is recommended for preventing HBV reactivation when IFX and immunosuppressants are synergistically used.

Objective To evaluate the efficacy and safety of thalidomide (100 to 200mg per day) in the treatment of adult refractory Crohn's disease (CD).Methods From July 2008 to February 2013,29 refractory CD patients were enrolled in thalidomide (100 to 200 mg per day)cohort study.The clinical activity was evaluated by simplified CD activity index.Patients in clinical remission underwent colon endoscope examination,and mucosal healing was assessed by simple endoscopic score for Crohn's disease (SES-CD).Adverse reactions (ADR) were also observed.Results Among the 29 CD patients,23 males and six females,the baseline of 19 patients (65.5％) were in clinical active period and 10 in clinical remission period.Among patients with baseline in clinical active period,three patients did not reach the target dose because of ADR,the left 16 patients were treated with thalidomide for one year and 14 patients achieved clinical remission.The median time of inducing clinical remission was one month.A totle of 24 patients with clinical remission induced by thalidomide and with baseline in clinical remission period were assessed in efficacy evaluation of mucosal healing.Thalidomide was withdrawn in three patients in six months because of ADR and colonoscopy evaluation did not complete,while the other 21 patients received colonoscopy evaluation among whom 33.3％ (7/21) achieved mucosal healing after two years of thalidomide treatment.Numbness of the hands,feet or mouth,somnolence and dermatitis were the top three ADR of thalidomide treatment.A total of nine patients withdrew the medication because of ADR (four (13.8％) with numbness of the hands,feet or mouth,four (13.8％) with dermatitis and one (3.4％) with leukopenia).Conclusions Thalidomide 100 to 200 mg per day can induce clinical remission and mucosal healing in refractory CD.However,it has some adverse reactions and close monitoring and follow up are required during treatment.