BACKGROUND & AIMS:Adverse events (AEs) including reactivation of herpes zoster (HZ) and venous thromboembolism (VTE) have been reported from clinical trials of tofacitinib in ulcerative colitis (UC). We investigated the incidence rates of AEs in a real-world study of UC patients given tofacitinib. METHODS:We collected data from 260 patients with UC in the Tofacitinib Real-world Outcomes in Patients with ulceratIve colitis and Crohn's disease consortium study, performed at 6 medical centers in the United States. Patients were followed up for a median of 6 months (interquartile range, 2.7-11.5 mo). AEs were captured using a standardized data collection instrument before study

Cholangiocytes, or bile duct epithelia, were once thought to be the simple lining of the conduit system comprising the intra- and extrahepatic bile ducts. Growing experimental evidence demonstrated that cholangiocytes are in fact the first line of defense of the biliary system against foreign substances. Experimental advances in recent years have unveiled previously unknown roles of cholangiocytes in both innate and adaptive immune responses. Cholangiocytes can release inflammatory modulators in a regulated fashion. Moreover, they express specialized pattern-recognizing molecules that identify microbial components and activate intracellular signaling cascades leading to a variety of downstream responses. The cytokines secreted by cholangiocytes, in conjunction with the adhesion molecules expressed on their surface, play a role in recruitment, localization, and modulation of immune responses in the liver and biliary tract. Cholangiocyte survival and function is further modulated by cytokines and inflammatory mediators secreted by immune cells and cholangiocytes themselves. Because cholangiocytes act as professional APCs via expression of major histocompatibility complex antigens and secrete antimicrobial peptides in bile, their role in response to biliary infection is critical. Finally, because cholangiocytes release mediators critical to myofibroblastic differentiation of portal fibroblasts and hepatic stellate cells, cholangiocytes may be essential in the pathogenesis of biliary cirrhosis.

Background and Aims Inflammation of the pouch after ileal pouch-anal anastomosis (IPAA) can significantly impact quality of life and be difficult to treat. We assessed the effectiveness and safety of vedolizumab in Crohn’s disease (CD) of the pouch and chronic antibiotic-dependent or antibiotic-refractory pouchitis. Methods This was a retrospective, multicenter cohort study at 5 academic referral centers in the United States. Adult patients with endoscopic inflammation of the pouch who received vedolizumab were included. The primary outcome was clinical response at any time point. Secondary outcomes included clinical remission, endoscopic response, and remission. Univariate analysis and multivariate analysis were performed for the effect of the following variables on clinical response: fistula, onset of pouchitis less than 1 year after IPAA, younger than 35 years old, gender, previous tumor necrosis factor inhibitor-alpha use, and BMI >30. Results Eighty-three patients were treated with vedolizumab for inflammation of the pouch between January 2014 and October 2017. Median follow-up was 1.3 years (interquartile range 0.7–2.1). The proportion of patients that achieved at least a clinical response was 71.1%, with 19.3% achieving clinical remission. Of the 74 patients with a follow-up pouchoscopy, the proportion of patients with endoscopic response and mucosal healing was 54.1% and 17.6%, respectively. Patients who developed pouchitis symptoms less than 1 year after undergoing IPAA were less likely to respond to vedolizumab, even after controlling for other risk factors. Conclusions Vedolizumab is safe and effective in the management of CD of the pouch and chronic pouchitis. Further studies are needed to compare vedolizumab with other biologic therapies for pouchitis and CD of the pouch.

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C urrently, 3 vaccines have been granted Emergency Use Authorization for coronavirus disease 2019 prevention in the United States. These include the messenger RNA (mRNA) platform vaccines (mRNA-1273; Moderna/National Institutes of Health) and BNT162b2 (Pfizer-BioNTech) and an adenovirus vector vaccine (Ad26.CoV2.S; Johnson & Johnson), which were 94%, 95%, and 67% effective against COVID-19 infection in their phase III registry trials against the endemic variants at the time, respectively. 1-3 All 3 vaccines target the viral spike (S) protein that facilitates severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry into host cells via its receptor binding domain, which interacts with angiotensin-converting enzyme 2. 4 Although the mRNA platform vaccines are 2-dose vaccines administered 3-4 weeks apart, the Ad26.CoV2.S is administered as a single dose. Another adenovirus vector vaccine (ChAdOx1; Astrazeneca), not yet authorized in the United States, is intended as a 2-dose regimen with an interval of 8-12 weeks.Patients with inflammatory bowel disease (IBD) on corticosteroids, immunomodulators, and advanced therapies may have normal to slightly decreased humoral responses to the SARS-CoV-2 mRNA vaccine platforms. 1 In addition, patients receiving infliximab and/or thiopurines have significantly lower rates of seroconversion than those on vedolizumab monotherapy after a single dose of either BNT162b2 or ChAdOx1. 2 A study of solid organ transplant recipients showed decreased humoral responses to Ad26.CoV2.S vaccine relative to both mRNA platform vaccines, although it is unknown whether these findings are generalizable to other immune compromised populations. 5 Q5 We aimed to assess for differences in serologic responses among patients with IBD who received Ad26.CoV2.S relative to those receiving mRNA-1273 or BNT162b2. Among 353 vaccine recipients with IBD participating in a prospective SARS-CoV-2 vaccine registry without prior COVID-19 infection and who had completed a full vaccine regimen, 148 (42%), 193 (55%), and 12 (3%) received mRNA-1273, BNT162b2, and Ad26.CoV2.S, respectively. Demographic and disease characteristics were similar across vaccine groups (mean age, 51 years, 62% were female) (Supplementary Table 1). Approximately 290 (83.1%) participants were on immune-modifying therapies (IMTs), as defined by receipt of advanced therapies (biologics or JAK inhibitors, 80.2%), immunomodulators (16.6%), and/or systemic corticosteroids (6.6%) at the time of initial vaccination. At least 2 weeks after completion of the vaccine regimen, positive antibody levels were detected in 121 (100%), 142 (99%), and 9 (90%) patients receiving mRNA-1273, BNT162b2, and Ad26.CoV2.S, respectively (Figure 1A). Quantitative log 10 (anti-Spike IgG