Background and aims: Many inflammatory bowel disease (IBD) patients do not respond to medical therapy. Tofacitinib is a first in class, partially selective inhibitor of Janus kinase, recently approved for treating patients with ulcerative colitis (UC). We describe our experience with the use of tofacitinib for treatment of patients with moderate-to-severe IBD. Methods: This is a retrospective, observational study of the use of tofacitinib in IBD. Patients with medically resistant IBD were treated orally with 5 mg or 10 mg twice daily. Clinical response and adverse events were assessed at 8, 26, and 52 weeks. Objective response was assessed endoscopically, radiologically, and biochemically. Results: 58 patients (53 UC, 4 Crohn’s, 1 pouchitis) completed at least 8 weeks of treatment with tofacitinib. 93% of the patients previously failed treatment with anti-TNF. At 8 weeks of treatment, 21 patients (36%) achieved a clinical response, and 19 (33%) achieved clinical remission. Steroid-free remission at 8 weeks was achieved in 15 (26%) patients. Of the 48 patients followed for 26 weeks, 21% had clinical, steroid-free remission. Of the 26 patients followed for 12 months, 27% were in clinical, steroid-free remission. Twelve episodes of systemic infections were noted, mostly while on concomitant steroids. One episode of zoster infection was noted during follow up. Conclusions: In this cohort of patients with moderate-to-severe, anti-TNF resistant IBD, tofacitinib induced clinical response in 69% of patients. 27% were in clinical, steroid-free remission by one year of treatment. Tofacitinib is an effective therapeutic option for this challenging patient population.

Summary Background Following induction therapy with a calcineurin inhibitor (CNI) in severe ulcerative colitis, transitioning to vedolizumab as maintenance therapy could be an option. Aim To report on the largest cohort of patients successfully induced with CNIs who were transitioned to vedolizumab maintenance therapy. Methods This is a retrospective observational study of adult patients with severe steroid‐refractory ulcerative colitis. Patients were included if they were induced with a CNI followed by maintenance therapy with vedolizumab between January 2014 and December 2018. The primary endpoint was colectomy‐free survival. Secondary endpoints included survival without vedolizumab discontinuation as well as clinical, steroid‐free and biochemical remission at week 14. Results A total of 71 patients (59% male) were treated with vedolizumab after induction therapy with CNIs for severe steroid‐refractory colitis. Patients were followed for a median time of 25 months (IQR 16‐36). Colectomy‐free survival rates from vedolizumab initiation were 93% at 3 months, 67% at 1 year and 55% at 2 years. At the end of induction with vedolizumab at week 14, 50% of patients were in clinical remission, and 62% of patients had a normal CRP. At 1 and 2 years following vedolizumab initiation, 43% and 28% of patients were still on vedolizumab respectively. Vedolizumab was dose escalated to infusions every 4 weeks in 44% of patients. The median time to dose escalation was 5.6 months (IQR 4.1‐8.2). No serious adverse events were recorded in our patient cohort. Conclusions Transitioning to vedolizumab following induction of remission with CNIs is effective and safe.

Background Chronic inflammation in ulcerative colitis (UC) is associated with the development of colorectal neoplasia (CRN). A group at St. Mark’s Hospital reported a novel cumulative inflammatory index that predicted the development of CRN in UC patients that we validated with an independent, well-described, matched, case-controlled cohort from the University of Chicago. Methods Cumulative inflammatory burden (CIB) was calculated by summing each histological inflammatory activity (HIA) score and multiplying it by the length of the surveillance interval. Persistency was defined by the number of surveillance episodes (with a severity score >2) divided by the total number of surveillance procedures. T tests compared the mean and maximum HIA scores, assessing mean and maximum severity, CIB, and persistency. Results Sixty-two UC patients (26 patients with CRN, 36 control patients without CRN) were analyzed. Fifty-five percent were men, mean disease duration was 20.6 years, and mean age at CRN diagnosis was 43.9. Of the CRN patients, 6 (23%) had colorectal cancer, 16 (62%) had low-grade dysplasia, and 4 (15%) had indefinite dysplasia. Using mean HIA scores, we found CIB to be statistically greater in CRN patients (P = 0.04). Using maximum HIA scores, we found CIB (P = 0.02), mean severity (P = 0.03), and persistency (P = 0.01) to be significantly greater in CRN patients. Maximum severity was numerically greater for mean and maximum HIA scores but did not reach significance. Conclusion Cumulative histologic inflammation is significantly associated with the development of CRN in UC patients. This suggests a management strategy of controlling inflammation to reduce the risk of CRN and may influence the selection of surveillance intervals.

OBJECTIVES: Patients with inflammatory bowel disease (IBD) are susceptible to Clostridioides difficile infections (CDIs), suffering from greater morbidity and mortality than the general population. Previous studies have proven the efficacy of oral vancomycin therapy in CDI, but there are no definitive guidelines to treat patients with IBD. We assessed the relationship between the length of vancomycin therapy and rates of CDI recurrence and reinfection in patients with IBD. METHODS: We compared rates of CDI recurrence and reinfection in Crohn's disease and ulcerative colitis (UC) patients receiving long-duration (LD) and short-duration (SD) oral vancomycin therapy, defined as 21–42 days and 10–14 days, respectively. Recurrence and reinfection were defined as positive C. difficile toxin assay by polymerase chain reaction within 8 weeks of the end of antibiotic therapy and after 8 weeks of the end of antibiotic therapy, respectively. The Fisher exact test was used to test for significance, and multivariate logistic regression models were constructed to control for other covariables. RESULTS: One hundred thirty-four patients with IBD (57 ulcerative colitis and 77 Crohn's disease) met inclusion criteria. LD vancomycin had a 1.8% incidence of CDI recurrence, compared with 11.7% in the SD vancomycin group (odds ratio = 0.13, P = 0.043). CDI reinfection rates and time to reinfection were not significantly different (LD 14.0% vs SD 16.9%, P = NS). Multivariate logistic regression models showed that treatment with LD vancomycin had lower odds for recurrence than SD vancomycin (odds ratio = 0.03, P = 0.021). DISCUSSION: LD vancomycin is associated with lower rates of CDI recurrence compared with SD vancomycin therapy. These results will help guide clinical decisions and the development of a prospective trial.

BACKGROUND: Anastomotic complications after restorative total proctocolectomy with IPAA for ulcerative colitis alter functional outcomes and quality of life and may lead to pouch failure. Routine contrast enema of the pouch assesses anastomotic integrity before ileostomy reversal, but its clinical use is challenged. OBJECTIVE: The purpose of this research was to assess the relationship among preoperative clinical characteristics, abnormal pouchography, and long-term pouch complications. DESIGN: This was a retrospective chart review. SETTINGS: The study was conducted at a tertiary care center between 2000 and 2010. PATIENTS: Ulcerative colitis patients with IPAA undergoing pouchography before ileostomy closure were included. MAIN OUTCOME MEASURES: Patient demographics, incidence of pouch-related complications, and findings on pouchogram were recorded. Primary outcome was pouch failure, defined as excision or permanent diversion of the ileoanal pouch. Independent predictors of pouch failure were determined by multivariate regression. RESULTS: A total of 262 patients with ulcerative colitis were included. Contrast extravasation was seen in 27 patients (10.3%): 14 (51.9%) were clinically asymptomatic at the time of pouchogram. Six (22.2%) of 27 patients with extravasation developed pouch failure despite normalization of the pouchogram before ileostomy closure. Forty patients (15.3%) were found to have pouch-anal anastomotic stenosis; only 1 developed pouch failure. Pre-IPAA serum albumin and hemoglobin levels were inversely associated with contrast extravasation (serum albumin: OR = 0.42; hemoglobin: OR = 0.77; p < 0.05). Contrast extravasation was associated with delayed takedown operation (average = 67 d), increased risk (OR = 5.25; p < 0.01), and shorter time (median = 32.0 vs 72.5 mo; HR = 5.88; p < 0.05) to pouch failure, as well as increased risk of pouch-related complications (p < 0.05). LIMITATIONS: The study was limited by its retrospective nature and small number of patients who developed pouch failure. CONCLUSIONS: Pouchography before ileostomy takedown is useful in identifying patients with ulcerative colitis at risk for postoperative complications. Radiologic resolution of IPAA-related leak does not reliably predict healing; caution is warranted in this subgroup. See Video Abstract at http://links.lww.com/DCR/A818.