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Background: Vedolizumab effectiveness estimates immediately after Food and Drug Administration (FDA) approval for ulcerative colitis (UC) and Crohn's disease (CD) are limited by use in refractory populations. We aimed to compare treatment patterns and outcomes of vedolizumab in 2 time frames after FDA approval., Methods: We used 2 data sets for time trend analysis, an academic multicenter vedolizumab consortium (VICTORY) and the Truven MarketScan database, and 2 time periods, May 2014-June 2015 (Era 1) and July 2015-June 2017 (Era 2). VICTORY cumulative 12-month clinical remission, corticosteroid-free remission, and mucosal healing rates, and Truven 12-month hospitalization and surgery rates, were compared between Eras 1 and 2 using time-to-event analyses., Results: A total of 3661 vedolizumab-treated patients were included (n = 1087 VICTORY, n = 2574 Truven). In both cohorts, CD and UC patients treated during Era 2 were more likely to be biologic naïve. Compared with Era 1, Era 2 CD patients in the VICTORY consortium had higher rates of clinical remission (31% vs 40%, P = 0.03) and mucosal healing (42% vs 58%, P < 0.01). These trends were not observed for UC. In the Truven database, UC patients treated during Era 2 had lower rates of inflammatory bowel disease-related hospitalization (22.4% vs 9.6%, P < 0.001) and surgery (17.2% vs 9.4%, P = 0.008), which was not observed for CD., Conclusion: Since FDA approval, remission and mucosal healing rates have increased for vedolizumab-treated CD patients, and vedolizumab-treated UC patients have had fewer hospitalizations and surgeries. This is likely due to differences between patient populations treated immediately after drug approval and those treated later., (© 2019 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.)

Background: We quantified loss of response (LOR) to vedolizumab (VDZ) in clinical practice and assessed the effectiveness of VDZ dose intensification for managing LOR., Methods: Retrospective review (May 2014-December 2016) of a prospectively maintained inflammatory bowel disease (IBD) registry. Kaplan-Meier estimates were used to determine rates of LOR to VDZ . Independent predictors of LOR were identified using univariate and multivariable Cox proportional hazard regression. Success of recapturing response (>50% reduction in symptoms from baseline) and remission (complete resolution of symptoms) after dose intensification was quantified., Results: Cumulative rates for VDZ LOR were 20% at 6 months and 35% at 12 months, with slightly lower rates in Crohn's disease than in ulcerative colitis (6 months 15% vs 18% and 12 months 30% vs 39%, P = 0.03). On multivariable analysis, LOR to a tumor necrosis factor (TNF) antagonist before VDZ use was associated with an increased risk for LOR to VDZ [hazard ratio (HR) 1.93; 95% confidence interval (CI) 1.25-2.97] in all patients. For Crohn's disease patients specifically, higher baseline C-reactive protein concentration was associated with increased risk for LOR to VDZ (HR 1.01 per mg/dL increase, 95% CI 1.01-1.02). Shortening of VDZ infusion interval from 8 to every 4 or 6 weeks recaptured response in 49% and remission in 18% of patients., Conclusions: LOR to a TNF antagonist before VDZ use and higher baseline C-reactive protein are important predictors of VDZ LOR. Treatment response can be recaptured in almost half of these patients with VDZ infusion interval shortening.

Background: Vedolizumab is now widely available for the treatment of moderate to severe ulcerative colitis (UC) and Crohn's disease (CD). We sought to quantify the rates of postoperative complications with preoperative vedolizumab compared with anti-tumor necrosis factor (anti-TNF) therapy., Methods: A multicenter retrospective review of adult inflammatory bowel disease (IBD) patients who underwent an abdominal operation between May 20, 2014, and December 31, 2015, was performed. The study cohort was comprised of patients who had received vedolizumab within 12 weeks of their abdominal operation, and the control cohort was IBD patients who had received anti-TNF therapy., Results: A total of 146 patients received vedolizumab within 12 weeks before an abdominal operation (64% female; n = 93; median age, 33 years; range, 15-74 years), and 289 patients received anti-TNF therapy (49% female; n = 142; median age, 36 years; range, 17-73 years). Vedolizumab-treated patients were younger (P = 0.015) and were more likely to have taken corticosteroids (P < 0.01) within the 12 weeks before surgery. Vedolizumab-treated patients had a significantly increased risk of any postoperative surgical site infection (SSI; P < 0.01), superficial SSI (P < 0.01), deep space SSI (P = 0.39), and mucocutaneous separation of the diverting stoma (P < 0.00) as compared with patients taking anti-TNF therapy. On multivariate analysis, after adjusting for body mass index, steroids at the time of operation, and institution, exposure to vedolizumab remained a significant predictor of postoperative SSI (P < 0.01)., Conclusions: We observed that vedolizumab-treated patients were at significantly increased risk of postoperative SSIs after a major abdominal operation, as compared with anti-TNF-treated patients.

Background: Clostridium difficile infection (CDI) is traditionally considered a colon-affecting disease with frequent pseudomembrane formation. However, multiple case reports have documented the existence of CDI in the small bowel, and the literature on outcome of C difficile enteropathy (CDE) is sparse. The aims of our study are to identify risk factors and to assess patient-related outcomes associated with CDE., Methods: This is a case-control study involving 112 patients at our tertiary care center. Patients with an ileostomy who tested positive for C difficile toxins were assigned to the study group (n = 34). The control group included patients with an ileostomy who tested negative for the C difficile toxins (n = 78). Via chart review, we collected data on baseline characteristics, laboratory values, potential risk factors, and outcome measures., Results: Patients in the study and control groups were comparable in baseline and laboratory characteristics. In univariate analysis, CDE was associated with a history of smoking (hazard ratio [HR], 2.1; 95% confidence interval [CI], 1.06-4.3; P = 0.034), the presence of alcohol use (HR, 3.7; 95% CI, 1.05-12.8; P = 0.042), and older median age at the time of ileostomy (HR, 1.2; 95% CI, 1.07-1.3; P = 0.001). In multivariate analysis, no significant association between established CDI risk factors (eg, prior exposure to antibiotics and the use of proton pump inhibitors or histamine 2 receptor blockers) and the risk for the CDE was found. Only a history of alcohol intake was found to be associated with CDE (HR, 3.9; 95% CI, 1.09-14.1; P = 0.036). No significant difference in mortality was found in the study and control groups (2.9% vs 1.3%, P = 0.52), but patients with CDE were more likely to have acute kidney injury (AKI) than those without CDE (odds ratio, 4.0; 95% CI, 1.2-13.0. P = 0.023)., Conclusions: We identified a history of alcohol use a risk factor for CDE. Furthermore, CDE was found be associated with an increased risk for developing AKI., (© 2018 Crohn’s & Colitis Foundation of America. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com)

Background: The administration of intravenous immunoglobulin (IVIG) has demonstrated promise in the treatment of medically refractory inflammatory bowel diseases (IBD). We aimed to identify factors associated with IVIG failures in the treatment of refractory IBD., Methods: Our historical cohort included patients with refractory IBD admitted to our inpatient service with an exacerbation and treated with at least 1 dose of IVIG (0.4 g/kg). Detailed clinical variables were recorded for subjects. Examined outcomes included changes in disease-specific severity indices, the duration of surgery-free survival after IVIG, infusion reactions, subsequent IBD-related emergency department visits, hospital readmissions, and mortality., Results: Fifty-four subjects with refractory IBD (61% female, age 42 ± 16 yrs, 23 with Crohn's disease, 15 with ulcerative colitis, 16 with pouchitis) met the inclusion criteria. All disease severity scores were significantly improved after IVIG administration (Harvey-Bradshaw index P = 0.007, partial Mayo score P = 0.002, modified Pouchitis Disease Activity Index P = 0.008). Twenty-seven patients (50%) underwent surgery, with a mean surgery-free survival of 28.7 ± 3.7 months. In univariable analysis, patients with Clostridium difficile infection (CDI) had a 3-fold increased risk of bowel resection surgery after IVIG compared with those without (hazard ratio = 2.9, 95% confidence interval, 1.2-7.4; P = 0.023), and in subsequent multivariable analysis, CDI remained significant (hazard ratio = 3.0, 95% confidence interval, 1.2-7.6; P = 0.024). CDI was also associated with increased risk of hospital readmission (hazard ratio = 2.5, 95% confidence interval, 1.05-5.9; P = 0.038)., Conclusions: Our study demonstrates that IVIG is beneficial in patients with medically refractory IBD, and that concomitant CDI is a risk factor for the treatment failure of IVIG for refractory disease.

Background: Diarrhea is a common problem in the setting of solid-organ transplantation, especially orthotopic liver transplant (OLT). De novo or preexisting inflammatory bowel disease (IBD) is one of the differential diagnoses. The aims of our study were to evaluate the frequency of de novo IBD in patients with OLT and to assess the impact of de novo IBD and preexisting IBD on the outcome of OLT., Methods: This case-control study included all eligible patients who had OLT from January 2001 to December 2009. The study group included all patients who had a biopsy-proven diagnosis of IBD after their OLT (the de novo IBD group). The control groups included patients with existing IBD before OLT and those without IBD before and after OLT. The groups were matched based on their underlying diagnoses of end-stage liver disease. Univariate and multivariate analyses were performed., Results: A total of 66 subjects were included in the study. The mean age was 45.4 ± 13.4 years, with 44 (66.7%) being male. Fifteen patients (23%) had de novo IBD, 21 (32%) had existing IBD before OLT, and 30 (45%) had no underlying IBD before or after OLT. There were no significant differences between the 2 IBD groups in any of the IBD characteristics, including IBD medications. Subjects without IBD were more likely to receive mycophenolate mofetil within 1 week of OLT than those in the de novo or preexisting IBD (70% versus 23% P = 0.018). Episodes of graft rejection were more commonly observed in subjects with preexisting IBD (52%) than de novo IBD (27%) or no IBD (20%) (P = 0.045). The rate of retransplantation was highest in the de novo IBD group followed by the preexisting IBD group and non-IBD group (20% versus 14% versus 0%; P = 0.029). Combined together, patients with IBD in the setting of OLT were more likely to be retransplanted than those without IBD (16.7% versus 0%, P = 0.045). In multivariate analysis, we found that patients with IBD were 6.7 (95% confidence interval, 1.9-23.9) times more likely to have an adverse outcome after liver transplant (P = 0.004), after adjusting for primary sclerosing cholangitis., Conclusions: De novo IBD can occur in patients after OLT. De novo IBD and preexisting IBD were found to be associated with a higher risk for graft failure, suggesting that early diagnosis and closer monitoring of the patients at risk are critical.

Despite recent therapeutic advances, patients with Crohn's disease (CD) continue to experience high recurrence with cumulative structural damage and ultimate loss of nutritional autonomy. With short bowel syndrome, strictures, and enteric fistulae being the underlying pathology, CD is the second common indication for home parenteral nutrition (HPN). With development of intestinal failure, nutritional management including HPN is required as a rescue therapy. Unfortunately, some patients do not escape the HPN-associated complications. Therefore, the concept of gut rehabilitation has evolved as part of the algorithmic management of these patients, with transplantation being the ultimate life-saving therapy. With type 2 intestinal failure, comprehensive rehabilitative measures including nutritional care, pharmacologic manipulation, autologous reconstruction, and bowel lengthening is often successful, particularly in patients with quiescent disease. With type 3 intestinal failure, transplantation is the only life-saving treatment for patients with HPN failure and intractable disease. With CD being the second common indication for transplantation in adults, survival outcome continues to improve because of surgical innovation, novel immunosuppression, and better postoperative care. Despite being a rescue therapy, the procedure has achieved survival rates similar to other solid organs, and comparable to those who continue to receive HPN therapy. With similar technical, immunologic, and infectious complications, survival is similar in the CD and non-CD recipients. Full nutritional autonomy is achievable in most survivors with better quality of life and long-term cost-effectiveness. CD recurrence is rare with no impact on graft function. Further progress is anticipated with new insights into the pathogenesis of CD and mechanisms of transplant tolerance.