An International Multicenter Comparison of IBD-Related Disability and Validation of the IBDDI.

BACKGROUND: The IBD disability index (IBDDI) has been shown to be valid and reliable. We compared the distributional and predictive properties of the IBDDI, when collected from five populations of people living with IBD- from Winnipeg, Chicago, Toronto, Hong Kong, and Jerusalem. METHODS: People with IBD from five jurisdictions were invited to complete a survey including the IBDDI, the World Health Organization Disability Assessment Scale, the Work and Social Adjustment Scale, the IBDQ, the Kessler-6 distress scale, and the Stanford presenteeism scale. Between sites, we compared the correlation between IBDDI and the other 4 measures of disability/quality of life/distress, and the association between IBDDI and presenteeism and having been hospitalized in the past year. RESULTS: There were 1121 participants from Winnipeg, 511 from Chicago, 147 from Toronto, 97 from Hong Kong, and 96 from Jerusalem. The majority had Crohn's disease. Although the mean IBDDI score varied by site, the correlation between IBDDI and each of the other 4 measures of disability/QOL/distress was nearly identical. Similarly, the regression coefficient showing the association between IBDDI and presenteeism was nearly identical in all sites, and the risk ratios showing the association between hospitalization and high IBDDI was similar in all sites. CONCLUSION: The correlation between IBDDI and different measures of disability/QOL/distress was similar across all sites. There is strong evidence of the association between IBD-related disability and presenteeism, and between hospitalization and high IBD-related disability, and that the associations are the same across different populations. The severity of disability that an individual with a given IBDDI score has is directly comparable across populations.

[TREATMENTS OF PERIANAL CROHN'S DISEASE].

INTRODUCTION: Perianal Crohn's disease is correlated with a significant decrease in quality of life and can predict unfavorable outcomes. In this condition, it is recommended that a multidisciplinary team including a gastroenterologist, colorectal surgeon and radiologist will be involved to optimize therapeutic decisions. Despite the advent of biologic and surgical therapies, the success rate of therapy is unsatisfactory and may result in a high chance of recurrence. In recent years, novel therapies have been introduced which include local injection of mesenchymal stem cells and surgical techniques which can improve the outcome and quality of life of the patients. The goal of this review, is to raise the awareness and summarize the therapeutic options available for the treatment of perianal Crohn's disease.

Clinical and Radiologic Characteristics of Intra-Abdominal Fistulizing Crohn's Disease.

BACKGROUND: Few studies describe the radiological and laboratory characteristics of patients with Crohn's disease (CD) with intra-abdominal fistulae. OBJECTIVES: We aimed to describe a cohort of CD patients with intra-abdominal fistulae and determine characteristics associated with complex fistulae. METHODS: Data were gathered from medical records and imaging studies of patients. Evaluation included type of fistula, number of fistulae, and radiological characteristics. RESULTS: A total of 205 fistulae in 132 patients were identified with an average patient age of 31 (±12) years. The average time from CD diagnosis to fistula development was 7 years. The most common type of fistula was entero-enteric (53%). Patients with an extra-intestinal fistula presented with an average of 1.96 fistulae, compared with an average of 1.28 fistulae for those with a fistula limited to the bowel (p =0.01). Except for the number of fistula no other significant differences were observed in radiological characteristics of patients who were diagnosed with a fistula at time of CD diagnosis compared to those diagnosed with a fistula later. CONCLUSIONS: The most common CD-associated intra-abdominal fistulae are entero-enteric and entero-colonic fistulae. An extra-intestinal fistula and diagnosis of a fistula subsequent to diagnosis of CD were associated with an increased number of fistulae per patient.

[DISABILITY AMONG PATIENTS WITH INFLAMMATORY BOWEL DISEASES: A CROSS SECTIONAL STUDY].

INTRODUCTION: nflammatory bowel diseases (IBD) which include Crohn's disease and ulcerative colitis cause chronic remitting inflammation of the gastrointestinal tract with the potential of bowel wall injury which can lead to disability. AIMS: This study aimed to evaluate the degree of disability among IBD patients in Israel using validated scales and to identify factors that are associated with disability. Furthermore, the study aimed to examine the association between disability and quality of life (QoL) among patients. METHODS: The study population included 96 patients who attended a dedicated IBD clinic, (71 patients (pts) with Crohn's disease (CD), 22 pts with ulcerative colitis (UC) and 3 pts with IBD-undefined (IBD-U)). The participants completed a 5-part questionnaire which included demographic parameters, a validated QoL measure (inflammatory bowel disease questionnaire (IBDQ), two validated disability scales (the work and social adjustment scale (WSAS) and the World Health Organization Disability Assessment Schedule V.2.0 (WHODAS2.0), employment status, and a disease activity measure (the Manitoba IBD index (MIBDI). RESULTS: Major disability was found among 20% of the participants (as defined by a WSAS score ≥17). Major disability was significantly associated with lower QoL (p<0.001) and with recognition of disability from the National Insurance Institute of Israel ("Hamosad Lebituach Leumi") (p=0.005). Significant association was found between WHODAS2.0 and low QoL (r=-0.763,p<0.001). There were no significant differences in rates of major disability among patients with CD vs. those with UC. CONCLUSIONS: Approximately one fifth of IBD patients in Israel have major disability, which in turn, is associated with a decreased quality of life and recognition of disability from the National Insurance Institute of Israel. There were no significant differences in rates of disability between patients with CD vs. those with UC.

G-EYE colonoscopy is superior to standard colonoscopy for increasing adenoma detection rate: an international randomized controlled trial (with videos).

BACKGROUND AND AIMS: Colorectal cancer (CRC) is largely preventable with routine screening and surveillance colonoscopy; however, interval cancers arising from precancerous lesions missed by standard colonoscopy still occur. An increased adenoma detection rate (ADR) has been found to be inversely associated with interval cancers. The G-EYE device includes a reusable balloon integrated at the distal tip of a standard colonoscope, which flattens haustral folds, centralizes the colonoscope's optics, and reduces bowel slippage. The insufflated balloon also aims to enhance visualization of the colon during withdrawal, thereby increasing the ADR. METHODS: In this randomized, controlled, international, multicenter study (11 centers), patients (aged ≥50 years) referred to colonoscopy for screening, surveillance, or changes in bowel habits were randomized to undergo either balloon-assisted colonoscopy by using an insufflated balloon during withdrawal or standard high-definition colonoscopy. The primary endpoint was the ADR. RESULTS: One thousand patients were enrolled between May 2014 and September 2016 to undergo colonoscopy by experienced endoscopists; 803 were finally analyzed (standard colonoscopy n = 396; balloon-assisted colonoscopy n = 407). Baseline parameters were similar in both groups. Balloon-assisted colonoscopy provided a 48.0% ADR compared with 37.5% in the standard colonoscopy group (28% increase; P = .0027). Additionally, balloon-assisted colonoscopy provided for a significant increase in detection of advanced (P = .0033) flat adenomas (P < .0001) and sessile serrated adenomas/polyps (P = .0026). CONCLUSION: Balloon-assisted colonoscopy yielded a higher ADR and increased the detection of advanced, flat, and sessile serrated adenomas/polyps when compared with standard colonoscopy. Improved detection by the G-EYE device could impact the quality of CRC screening by reducing miss rates and consequently reducing interval cancer incidence. (Clinical trial registration number: NCT01917513.).

To Pull or to Scope: A Prospective Safety and Cost-effectiveness of Percutaneous Endoscopic Gastrostomy Tube Replacement Methods.

BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) tubes are routinely used as an effective method for providing enteral nutrition. The need for their exchange is common. GOALS: We aimed to examine the comparative safety and cost-effectiveness of PEG percutaneous counter-traction "pulling" approach or by endoscopically guided retrieval. STUDY: A prospective 215 consecutive patients undergoing PEG tube insertion were included. Fifty patients in total were excluded. The patients were examined for demographics, indications for PEG replacement, as well as procedure-related complications and procedural costs. RESULTS: Group A included 70 patients (42%) with PEG tubes replaced endoscopically, whereas group B included 95 patients (58%) with PEG tubes replaced percutaneously. Baselines characteristics were similar between the 2 groups (P=NS). Group A and group B had similar immediate complication rates including 4 patients in group B (4.2%), and 2 patients in group A (2.8%) (P=0.24). Complications included a conservatively managed esophageal perforation, and self-limited mild bleeding groups A and group B, respectively. The mean procedure cost was significantly higher in the endoscopic PEG replacement group compared with the percutaneous PEG replacement group ($650 vs. $350, respectively). CONCLUSION: Percutaneous PEG replacement appears as safe as endoscopic PEG replacement, however, percutaneous tube exchange is less costly.

Isolation and expansion of high yield of pure mesenchymal stromal cells from fresh and cryopreserved placental tissues.

The injection of placental stromal cells isolated from fetal human tissues (f-hPSC) was reported to indirectly induce tissue regeneration in different animal models. A procedure of f-hPSC isolation from fragments of both selected fresh or cryopreserved bulk placental neonate tissues is proposed, based on their high migratory potential,. The fragments of the desired fetal placental tissues are adhered to a culture dish by traces of diluted fibrin and covered with culture medium. Spontaneous migration of pure f-hPSC from the tissue fragments to the cell culture dishes is followed by their rapid expansion by numerous passages. The isolated f-hPSC express typical mesenchymal surface antigens, including CD29, CD105, CD166 and CD146, with negative expression of white blood cell lineage and endothelial cells markers. Optimal yields of f-hPSC cultures can also be obtained from tissue samples cryopreserved in medium composed of 10% dimethyl sulfoxide (M2SO) and 50% fetal calf serum. Slightly better yields are obtained with media supplemented with 1% human albumin. Medium with 5% M2SO and/or 0.25 mg/ml PEG yielded inferior results. The f-hPSC from fresh or cryopreserved tissues express similar cell markers and growth kinetics. The proposed isolation protocol may also be applied for high yield isolation of stromal cells from fresh and cryopreserved tissue of other organs.

Diagnosis of Cytomegalovirus Infection during Exacerbation of Ulcerative Colitis.

BACKGROUND/AIMS: The role of cytomegalovirus (CMV) reactivation during exacerbations of ulcerative colitis (UC) is yet a matter of debate, and assessment of CMV infection in UC patients remains an ongoing challenge. We aimed to identify associated parameters and compare detection methods for CMV infection during UC exacerbation. METHODS: Clinical, pathological and virological parameters were retrospectively analyzed in all patients hospitalized in our institution for UC exacerbation between January 2009 and April 2015, who underwent full evaluation for CMV infection in colonic tissue by histopathology, immunohistochemistry (IHC) and CMV-PCR. RESULTS: Of 28 patients who underwent full examination for tissue CMV-infection, 13 (46.4%) were found to be positive for CMV. Tissue CMV-PCR was more sensitive for the detection of CMV infection than histopathology and IHC. CMV-positive patients had a statistically higher frequency of recent steroid treatment and fever, with higher mean partial Mayo scores and lower mean albumin levels. There were no significant differences between CMV-positive and CMV-negative patients in terms of age, severity of colitis and disease duration. In a multivariable model, only recent steroid treatment and fever were independently associated with colonic CMV infection. CONCLUSIONS: This study provides a clinical model to detect the presence of CMV infection in patients hospitalized with UC exacerbation, which could direct proper investigation and facilitate timely empirical therapy.

Ameliorating Active Ulcerative Colitis via an Orally Available Toll-Like Receptor-9 Modifier: A Prospective Open-Label, Multicenter Phase II Trial.

BACKGROUND: Treatment of active ulcerative colitis is associated with incomplete efficacy, adverse events, and loss of response. Toll-like receptor-9 mediates innate and adaptive immune response toward intestinal microorganisms. The oral synthetic oligonucleotide toll-like receptor-9 modulator has demonstrated anti-inflammatory properties in colitis murine models and a satisfactory safety profile in humans. AIM: To evaluate the efficacy and safety of BL-7040 (a Toll-like receptor-9 modulator) in patients with moderately active ulcerative colitis. METHODS: Moderately active ulcerative colitis patients were included in this multicenter, open-label phase IIa trial. Concomitant mesalamine and steroids at a stable dose were allowed. Clinical outcome was evaluated using the Mayo score, histology, and mucosal cytokine levels. Side effects were registered. RESULTS: Sixteen out of 22 patients completed a 5-week treatment course and 2-week follow-up. Six patients discontinued the study, three of them due to adverse events. Clinical remission was observed in two patients (12.5 %), and clinical response as well as mucosal healing were achieved in half (50 %) of the patients, while all others remained stable. Furthermore, mucosal neutrophil (p = 0.002) and mucosal interleukin-6 levels (p = 0.046) were significantly reduced in responders compared to non-responders. Toll-like receptor-9 was well tolerated with only one unrelated to study drug serious adverse event (hemoglobin decrease) and 29 mild-to-moderate adverse events. CONCLUSIONS: Oral administration of the Toll-like receptor-9 agonist BL-7040 appeared efficacious, safe and well tolerated in patients with moderately active ulcerative colitis.

Younger age at diagnosis is associated with panenteric, but not more aggressive, Crohn's disease.

BACKGROUND & AIMS: Crohn's disease (CD) diagnosed in pediatric patients has been reported to have a more aggressive phenotype and course, with a greater prevalence of upper gastrointestinal involvement, than in adults. However, studies have not accounted for differences in diagnostic tests. We aimed to discern whether, in fact, CD diagnosed in childhood has a different outcome than CD diagnosed in adults. METHODS: We performed comprehensive medical chart reviews of 571 patients with CD (451 with complete data) who were followed in a single referral inflammatory bowel disease clinic in Winnipeg, Canada, from 1993-2012. For specific time intervals, we determined types and numbers of imaging studies performed and parameters of disease phenotype, including age at diagnosis according to the Montreal classification (A1 diagnosed <17 years of age, A2 diagnosed 17-40 years, and A3 diagnosed >40 years). RESULTS: Within 1 year of diagnosis, a higher proportion of A1 patients had upper gastrointestinal involvement and ileocolonic (L3) disease than A2 or A3 patients. These differences could be partly accounted for by the diagnostic tests performed during this time period. Although A1 patients underwent more extensive imaging studies, they had a lower prevalence of complicated disease, particularly compared with A3 patients. After a median follow-up period of 11.1 years, complicated disease behavior (B2 [structuring] or B3 [penetrating]) was similar among the 3 groups. Nonetheless, at the end of the study period, rates of inflammatory bowel disease-related abdominal surgery were significantly lower for A1 than A2 patients (odds ratio, 0.63; 95% confidence interval, 0.41-0.98) but not for A3 patients (odds ratio, 0.71; 95% confidence interval, 0.40-1.27). CONCLUSIONS: On the basis of a database analysis of different age groups of patients with CD, studies of disease phenotypes among different cohorts should account for different patterns of diagnostic imaging evaluation. Our data show that although children are at increased risk of panenteric disease, they are not more likely to have more complicated disease or undergo surgery than adults.

Low prevalence of disability among patients with inflammatory bowel diseases a decade after diagnosis.

BACKGROUND & AIMS: Disability is defined by chronic limitations that preclude the ability to engage in usual daily activities. Studies of disability in patients with inflammatory bowel disease (IBD) have focused on work and employment, with few descriptions of more general disability among multiple domains. We examined disability and the factors associated with it a decade after diagnosis in a population-based cohort of IBD patients. METHODS: We interviewed 125 patients with Crohn's disease (CD) and 119 with ulcerative colitis (UC) from the population-based Manitoba IBD Cohort study a median of 12.3 years after diagnosis. Disability was assessed by using 2 validated measures. Disease activity was assessed semiannually, and long-term activity was defined as symptoms of active IBD at more than 65% of semiannual assessments. RESULTS: Mean levels of disability were significantly higher among patients with CD than those with UC (P < .01). On the basis of the Work and Social Adjustment Scale, rates of disability were 19% among patients with CD vs 11% among those with UC (P < .05). Results from the World Health Organization Disability Assessment Schedule v.2 and the Work and Social Adjustment Scale correlated (r = 0.58 for patients with CD and 0.60 for those with UC; P < .01). Disability was associated with reduced quality of life. Long-term active disease and a lifetime history of major depression were associated with disability, whereas history of IBD-related surgeries or hospitalizations was not. CONCLUSIONS: A minority of patients with IBD have significant disability after a decade of disease, although a higher proportion of patients with CD are disabled than those with UC. Long-term active disease and psychological factors are important predictors of disability. Depression should be treated as aggressively as the IBD itself.

Placental Histopathological Lesions and Adverse Neonatal Outcomes in Patients with Inflammatory Bowel Diseases- A retrospective Cohort Study.

Inflammatory bowel diseases (IBD) are significantly associated with adverse pregnancy and neonatal outcomes, though the pathomechanism is yet unknown. To investigate the relationship between IBD and adverse pregnancy outcomes by comparing neonatal outcomes and placental histopathology in two matched groups of patients with and without IBD. In this retrospective study, data of all patients who gave birth between 2008-2021 and were diagnosed with IBD were reviewed and compared to a control group matching two control cases for every IBD case. Neonatal outcomes and placental pathology were compared between the groups. Compared to the control group (n=76), the placentas of patients with IBD (n=36) were characterized by significantly lower placental weight (p < 0.001), and higher rates of maternal vascular malperfusion lesions (MVM, p < 0.001) and maternal and fetal inflammatory response lesions (p < 0.001). Neonates of patients with IBD were more frequently small for gestational age (SGA) (p=0.01), with increased rates of need for phototherapy (p = 0.03), respiratory morbidity and NICU admission (p < 0.001 for both outcomes). Multivariate logistic regression analyses adjusting for possible confounders (including maternal age, gestational age, chronic hypertension, smoking, and thrombophilia) confirmed the independent association between IBD and composite MVM lesions (aOR 4.31, p < 0.001), maternal inflammatory responses (aOR 40.22, p < 0.001) and SGA infants (aOR 4.31, p = 0.013). IBD is associated with increased rates of placental histopathological lesions and adverse pregnancy outcomes, including SGA infants. These novel findings imply the role of placental malperfusion and inflammatory processes in pregnancy complications of IBD patients, which should be followed accordingly. Approval of local ethics committee # WOMC-0219-20.

The diagnostic accuracy of endoscopic ultrasound vs. contrast-enhanced computed tomography in local staging of pancreatic adenocarcinoma: a bi-national multicenter study.

BACKGROUND: Identification of pancreatic cancer (PC) local invasion is crucial to optimize patients' selection for surgery. AIMS: To determine the diagnostic accuracy of contrast-enhanced computed tomography (CECT) and endoscopic ultrasound (EUS) in local staging of PC. METHODS: We performed a multicenter study including all patients with PC who underwent surgery. RESULTS: One hundred twelve patients were included. Surgical findings of peri-pancreatic lymph nodes (LN), vascular and adjacent organ involvement were seen in 67 (59.8%), 33 (29.5%) and 19 patients (17%), respectively. The diagnostic performance of EUS was better than CECT in peri-pancreatic LN. The sensitivity, specificity, positive predictive value (PPV) and negative predictive (NPV) of CECT vs. EUS were 28.4%, 80%, 67.9% and 42.9% vs. 70.2%, 75.6%, 81% and 63%, respectively. For vascular and adjacent organ involvement, the sensitivity, specificity, PPV and NPV were 45.5%, 93.7%, 75%, 80.4% and 31.6%, 89.2%, 37.5% and 86.5% for CECT, respectively, vs. 63.6%, 93.7%, 80.8%, 86.1% and 36.8%, 94.6%, 58.3% and 88% for EUS, respectively. Combining both CECT and EUS, the sensitivity for peri-pancreatic LN, vascular and adjacent organ involvement improved (76.1%, 78.8% and 42%), respectively. CONCLUSION: EUS was superior to CECT in local staging. Combined EUS and CECT had a higher sensitivity than either alone.

Losartan reduces trinitrobenzene sulphonic acid-induced colorectal fibrosis in rats.

BACKGROUND: Intestinal fibrosis is a challenging clinical condition in several fibrostenosing enteropathies, particularly Crohn's disease. Currently, no effective preventive measures or medical therapies are available for intestinal fibrosis. Fibrosis, due to an abnormal accumulation of extracellular matrix proteins, is a chronic and progressive process mediated by cell/matrix/cytokine and growth factor interactions, but may be a reversible phenomenon. Of the several molecules regulating fibrogenesis, transforming growth factor-beta 1 (TGF-b1) appears to play a pivotal role; it is strongly induced by the local activation of angiotensin II. The levels of both TGF-b1 and angiotensin II are elevated in fibrostenosing Crohn's disease. AIMS: To evaluate the in vivo effect of losartan - an angiotensin II receptor antagonist - on the course of chronic colitis-associated fibrosis and on TGF-b1 expression. METHODS: Colitis was induced by intrarectal instillation of trinitrobenzene sulphonic acid (TNBS) (15 mg/mL) while losartan was administered orally daily by gavage (7 mg/kg/day) for 21 days. Three groups of rats were evaluated: control (n=10); TNBS treated (n=10); and TNBS + losartan treated (n=10). Inflammation and fibrosis of the colon were evaluated by macro- and microscopic score analysis. Colonic TGF-b1 levels was measured using ELISA. RESULTS: Twenty-one days after induction, losartan significantly improved the macro- and microscopic scores of fibrosis in the colonic wall and reduced TGF-b1 concentration. CONCLUSIONS: Prophylactic oral administration of losartan reduces the colorectal fibrosis complicating the TNBS-induced chronic colitis, an effect that appears to be mediated by a downregulation of TGF-b1 expression.

Improved Outcomes of Paediatric and Adult Crohn's Disease and Association With Emerging Use of Biologics-A Nationwide Study From the Epi-IIRN.

BACKGROUND: The effectiveness of biologics for improving long-term outcomes in patients with Crohn's disease [CD] is still controversial. In this nationwide study, we aimed to evaluate trends of long-term outcomes in all CD patients in Israel during the biologics era. METHODS: Trends of outcomes were analysed using data from the four Israeli health maintenance organisations, covering 98% of the population; joinpoint regression models were used to explore changes of these trends over 2005 to 2019. RESULTS: A total of 16 936 patients were diagnosed with CD in Israel since 2005 (2932 [17%] paediatric onset, 14 004 [83%] adult onset) with 114 947 person-years of follow-up. The cumulative rate of any CD related surgery was 5%, 9%, 11%, and 14% at 1, 3, 5, and 10 years from diagnosis. The increase in use of biologics was sharp (from 8.9% to 36%; average annual percent change [AAPC], 14.3%), and the time to biologics was shorter in recent years (median time of 4.8 [1.9-8.1] years in those diagnosed in 2005-2008 compared with 0.5 [0.2-1.1] years in those diagnosed in 2015-2018; p < 0.001). A significant decrease was noted in the hazard of hospitalisations (1.3 [0.1-4.6] years compared with 0.2 [0.02-0.9] years; p < 0.001), steroid dependency (1.5 [0.2-5.4] years compared with 0.1 [0.02-0.4] years; p < 0.001), and intestinal surgeries [4.7 [1.6-8.2] years compared with 0.6 [0.2-1.4] years; p < 0.001), but not of perianal surgery (4.2 [1.1-7.7] years compared with 0.6 [0.2-1.4] years; p = 0.2). Outcomes were consistently worse in paediatric onset compared with adults. CONCLUSIONS: The rates of hospitalisations, steroid dependency, and intestinal resections decreased in association with increased use of biologics both in children and in adults, but not the rate of perianal surgeries.

Short-term effectiveness and safety of tofacitinib in ulcerative colitis - real world data from tertiary medical centers in Israel.

BACKGROUND: We sought to define the effectiveness and safety of tofacitinib in a real-world (RW) cohort of Israeli patients with moderate to severe ulcerative colitis (UC). METHODS: This was a multi-center retrospective observational cohort study (2019-2020) to assess the effectiveness and safety of tofacitinib induction and maintenance therapy up to 26 weeks. Clinical response and remission were defined as a reduction in Simple Clinical Colitis Activity Index (SCCAI) or partial Mayo score (PMS) of ≥3 points, and SCCAI ≤2 or a PMS ≤1, respectively. RESULTS: We included 73 patients, 47% male; median age 26 years [IQR: 19.5-39.5], disease duration 7 years [IQR: 2.5-14.5], follow-up 7.1 months [IQR: 3-12], 91% biologics-experienced, and 74% ≥ 2-biologics. Half of patients used concomitant corticosteroids (CS). Overall, 56.1% discontinued therapy due to either lack of response and/or adverse events (AEs), median time to discontinuation - 9.7 months [IQR 3.4-16]. Overall, response, remission, and CS-free-remission were achieved in 47.6%, 20.6%, and 17.5% of patients, respectively. At early maintenance (week 26), response, remission, and CS-free-remission were achieved in 65%, 22.5%, and 20% of patients, respectively. At week 26, tofacitinib 10 mg BID was still used in 43%. Seventeen patients (23.2%) had an adverse event including herpes zoster- 2.7%, hospitalization- 12.3%, and colectomy- 2.7%. CONCLUSIONS: Tofacitinib was effective in achieving CS-free-remission in about 1/5 of highly biologics -experienced patients with UC. Despite a considerable proportion of patients maintained on tofacitinib 10 mg bid, it was well tolerated and safe. Earlier positioning of tofacitinib in the therapeutic algorithm may result in improved outcomes.