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Introduction: Real-world data on tofacitinib's effectiveness is limited and mainly retrospective or registry-based. We elected to conduct a pragmatic prospective study to assess the efficacy of tofacitinib for moderate to severe ulcerative colitis (UC), aiming to evaluate the ability of intestinal ultrasound (IUS) to discriminate responders vs. non-responders in real-time., Methods: This pragmatic prospective clinical study included consecutive adult patients starting tofacitinib treatment for active moderate to severe UC. Patients were evaluated at baseline and after 8 weeks of tofacitinib (clinical, biomarker, endoscopy, and IUS). The primary outcome was clinical response defined by a decrease in the full Mayo score (fMS) of ≥3 at week 8. Next, we explored ultrasonographic parameters in the sigmoid colon as potential real-time classifiers to differentiate between responders and non-responders at week 8., Results: Overall, 30 adult patients started tofacitinib; the median age was 26.3 years (IQR 22.5-39.8), and 50% were female. Most patients (86.6%) had left-sided or extensive colitis, 96.7% had previously failed biologic therapy, and 60% (18/30) were on oral corticosteroids at the start of tofacitinib. At week 8, clinical response (a decrease in the fMS ≥ 3) and remission (fMS ≤ 2) rates were 40% (12/30) and 20% (6/30), respectively. Biomarker response (FC < 250µg/g) and biomarker normalization (FC ≤ 100µg/g) were achieved in 47.6% (10/21) and 38.1% (8/21) of patients, respectively. Endoscopic healing (endoscopic Mayo sub-score [EMS] ≤ 1) was achieved in 33.3% (10/30) of patients. Sigmoid bowel wall normalization as assessed by IUS (sBWT ≤ 3) was achieved in 18.2% (4/22). The best sBWT cut-off at week 8 to accurately classify endoscopic healing vs. no healing was a sBWT of 3.6 mm (AUC of 0.952 [95% CI: 0.868-1.036], p  < 0.001)., Conclusion: In this real-world pragmatic prospective study, tofacitinib was an effective treatment for moderate to severe UC, and IUS at week 8 accurately discriminated treatment response from non-response.

Background: Patients with ulcerative colitis (UC) undergoing proctocolectomy and ileal pouch-anal anastomosis (IPAA) may eventually require biologic therapy. Factors associated with biologic therapy after IPAA have not been previously studied., Methods: All patients with UC after total proctocolectomy and IPAA who were followed at Rabin Medical Center comprehensive pouch clinic and who consented to prospective observational follow-up were included. The primary outcome was the initiation of biologic therapy after IPAA. Cox proportional hazard models were used to evaluate potential associations., Results: Out of 400 patients receiving their care at the pouch clinic, 148 patients consented to prospective observational follow-up and constituted the study cohort. The median age at diagnosis was 21 years and the age at IPAA was 30 years. Median time-to-biologic therapy initiation post-IPAA was 9.2 years, with 34 patients (23%) initiating biologic therapy: Associated factors for initiating biologic therapy post-IPAA were preoperative treatment with biologic therapy and immunomodulatory therapy (hazard ratio [HR] 6.1 and 3.6, respectively, P < .001); Arab descent (HR 5.3, P < .001); heterozygosity of NOD2 variant rs2066845 (HR 5.1, P = .03); past smoking status (HR 2.3, P = .03); 3-stage IPAA (HR 2.3, P = .02); immediate postoperative complications (HR 2.1, P = .033); and pediatric-onset UC (HR 2.1, P = .03). None of the patients undergoing IPAA due to dysplasia (n = 27) required biologic therapy., Conclusions: Several demographic, disease-related, surgery-related, and genetic factors associated with post-IPAA biologic therapy were identified. Physicians treating patients with UC undergoing colectomy should incorporate these factors into their decision-making process. These patients may benefit from closer postoperative follow-up, and earlier initiation of biologic therapy should be considered., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Introduction: Complicated perianal disease (cPD) may be the sole presentation of Crohn's disease (CD). The role of small-bowel capsule endoscopy (SBCE) in the diagnostic algorithm of cPD is unclear. We aimed to evaluate the role of SBCE as a diagnostic tool, in patients with cPD, after a negative standard workup for CD., Methods: A multicenter, retrospective, cross-sectional study, in patients with cPD, and negative standard workup for CD (ileocolonoscopy and cross-sectional imaging), who underwent SBCE for suspected CD. Demographics, biomarkers, and the Lewis Score (LS) were recorded and analyzed. An LS ≥ 135 was considered a positive SBCE for diagnosing CD., Results: Ninety-one patients were included: 65 (71.4%) males; median age: 37 (29-51) years; cPD duration: 25.1 (12.5-66.1) months. Positive SBCE: 24/91 (26.4%) patients. Fecal calprotectin (FC) positively correlated with LS ( r = 0.81; p < 0.001). FC levels of 100 µg/g and 50 µg/g had a sensitivity of only 40% and 55% to rule out small-bowel CD, with a negative predictive value (NPV) of only 76% and 80%, respectively., Conclusions: SBCE contributed to CD diagnosis in a quarter of patients with cPD after a negative standard workup. FC levels correlated with the degree of inflammation defined by the LS. However, the NPV of FC was low, suggesting that SBCE should be considered for patients with cPD even after a negative standard workup.

Background: The modified pouchitis disease activity index (mPDAI) based on clinical symptoms and endoscopic findings is used to diagnose pouchitis, but validated instruments to monitor pouchitis are still lacking. We recently established an endoscopic classification that described 7 endoscopic phenotypes with different outcomes. We assessed symptoms and compared mPDAIs among phenotypes in inflammatory bowel disease (IBD)., Methods: We retrospectively reviewed pouchoscopies and classified them into 7 main phenotypes: normal ( n  = 25), afferent limb (AL) involvement ( n  = 4), inlet involvement ( n  = 14), diffuse ( n  = 7), focal inflammation of the pouch body ( n  = 25), cuffitis ( n  = 18), and pouch-related fistulas ( n  = 10) with a single phenotype were included. Complete-case analysis was conducted., Results: One hundred and three IBD patients were included. The median mPDAI was 0 (IQR 0-1.0) in patients with a normal pouch. Among inflammatory phenotypes, the highest median mPDAI was 4.0 (IQR 2.25-4.75) in cuffitis, followed by 3.0 (IQR 2.5-4.0) in diffuse inflammation, 2.5 (IQR 1.25-4.0) in inlet involvement, 2.5 (IQR 2.0-3.5) in AL involvement, 2.0 (IQR 1.0-3.0) in focal inflammation, and 1.0 (IQR 0.25-2.0) in the fistula phenotype. Perianal symptoms were frequently observed in pouch-related fistulas (8/10, 80%) and cuffitis (13/15, 87%). Among patients with cuffitis, all had incomplete emptying (6/6, 100%)., Conclusions: We correlated the mPDAI with the endoscopic phenotypes and described the limited utility of symptoms in distinguishing between inflammatory phenotypes. Further studies are warranted to understand which symptoms should be monitored for each phenotype and whether mPDAI can be minimized after pouch normalization., Competing Interests: S.A., J.E.O., N.A.C., V.R., L.R.G., Y.Y., C.T., J.R., K.B.S., R.D.H., K.U., B.D.S., N.H.H., and A.S. have no relevant disclosures. R.D.C. is on the speaker’s bureau from AbbVie and Takeda. He is a consultant/advisor for AbbVie Laboratories, BM/celgene, Eli Lilly, Gilead Sciences, Janssen, Pfizer, Takeda, UCB Pharma. He has received clinical trial support/grants from Abbvie, BMS/Celgene, Boehringer Ingelheim, Crohn’s and Colitis Foundation of America, Genentech, Gilead Sciences, Hollister, Medimmune, Mesoblast Ltd., Osiris Therpeutics, Pfizer, Receptos, RedHill Biopharma, Sanofi-Aventis, Schwarz Pharma, Seres Therapeutics, Takeda Pharma, UCB Pharma. His wife is on the board of directors of Aerpio Therapeutics, Novus Therapeutics, Vital Therapeutics, Inc, and NantKwest. M.A.R. has served as a consultant for Pfizer. S.R.D. has served as a consultant for Pfizer and is on the speaker’s bureau for AbbVie. J.P. has received grant support from AbbVie and Takeda. He has served as a consultant for Veraste,. CVS Caremark and is on the advisory board for Takeda, Janssen and Pfizer. E.B.C. is the founder and chief medical officer of AVnovum Therapeutics. D.T.R. has received grant support from Takeda; and has served as a consultant for Abbvie, Altrubio, Amgen, AvaloTherapeutics, Bristol-Myers Squibb, Buhlmann Diagnostics Corp, Chronicles Health, ClostraBio, Connect BioPharma, Cytoki Pharma, Douglas Pharmaceuticals, EcoR1, Ferring Pharma, Image Analysis Group, Index Pharmaceuticals, Iterative Health, Janssen Pharmaceuticals, Lilly, Odyssey Therapeutics, Pfizer, Prometheus Biosciences, Reistone Biopharma, Samsung Neurologica, Sangamo Therapeutics, Shanghai Pharma Biotherapeutics USA, Takeda, Tissium S.A., and Trellus Health., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn's & Colitis Foundation.)

Background & Aims: Janus kinase (JAK) inhibitors are used for treating inflammatory bowel diseases (IBD). We aimed to identify molecular effects of JAK inhibition in human intestinal mucosa, considering IBD location and phenotype., Methods: Colonic and ileal explants from patients with ulcerative colitis (UC), Crohn's disease (CD), and non-IBD controls (NC) were assessed for phosphorylated signal transducers and activators of transcription (p-STAT) levels and Inflammatory genes expression panel in response to ex-vivo JAK inhibitor (tofacitinib). Cytokine production by lamina propria lymphocytes in response to tofacitinib was assessed. Human intestinal organoids were used to investigate JAK inhibitors' effects on iNOS expression., Results: Explants were collected from 68 patients (UC=20; CD=20; NC=28). p-STAT1\3\5 inhibition rates varied, being higher in colonic compared to ileal explants. p-STAT1\3 inhibition rates negatively correlated with CRP levels. While significant alterations in 120 of 255 inflammatory genes were observed in colonic explants, only 30 were observed in ileal NC explants. In colonic explants from UC, significant alterations were observed in 5 genes, including NOS2. JAK inhibition significantly decreased Th1\Th2\Th17-related cytokine production from lamina propria lymphocytes. Various JAK inhibitors reduced IFN-γ-induced increase in iNOS expression in organoids., Conclusions: Site-specific anti-inflammatory effect of JAK inhibition by tofacitinib was noticed, whereby the colon was more robustly affected than the ileum. Ex-vivo response to tofacitinib is individual. JAK inhibition may attenuate inflammation by decreasing iNOS expression. Ex-vivo mucosal platforms may be a valuable resource for studying personalized drug effects in patients with IBD., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objective: Drug sustainability (DS), a surrogate marker for drug efficacy, is important, especially when aiming for precision medicine. However, it lacks reliable prediction methods., Aims: To develop and externally validate a web-based artificial intelligence(AI)-derived tool for predicting DS of infliximab and vedolizumab in patients with moderate-to-severe Ulcerative Colitis (UC)., Methods: Data from three Israeli centers included infliximab or vedolizumab patients treated for >54 weeks. Sustainability meant no corticosteroids, hospitalizations or surgeries. Machine learning techniques predicted >54-week and overall DS using baseline clinical data., Results: The model was developed using data from 246 patients from Rabin Medical Center and externally validated on 67 patients from Rambam Health Care Campus and Sheba Medical Center. No significant difference in DS was observed across the datasets. Most patients were biologic-naïve and primarily treated with vedolizumab. The model performed well, with an area under the ROC curve of 0.86, and showed good accuracy (65.5 %-76.9 %) across the test sets., Conclusions: The study introduces a novel, AI-based tool for predicting >54-week DS of infliximab and vedolizumab in moderate-to-severe UC, using baseline parameters. This can aid clinical decision-making in the framework of precision medicine, promising to optimize disease management while maintaining physician autonomy., Competing Interests: Conflicts of interest HY- Has received research grants from Pfizer; consulting fees from Abbvie, Janssen, Pfizer, Takeda, and BMS; Speaker fees from Abbvie, Janssen, Pfizer, Takeda, and Bristol Myers Squibb; Data Safety Monitoring Board or Advisory Board fees from Abbvie, Pfizer Takeda and Bristol Myers Squibb. JEO- Has received grant support from Pfizer, consulting fees from Takeda, and speaker fees from Abbvie, Janssen, Pfizer, Takeda, Novartis, and Bristol Myers Squibb. IAB- Has received speaker fees from Abbvie, Janssen, Pfizer, Takeda, and Neopharm. ID- consultation fee or honorarium from: Abbott, Abbvie, Athos, Arena, Altman Research, Cambridge Healthcare, Celltrion, Celgene/BMS, Eli-Lilly, Ferring, Falk Pharma, Food Industries Organization, Gilead, Galapagos, Iterative Scopes, Integra Holdings, Janssen, Neopharm, Pfizer, Rafa laboratories, Roche/Genentech, Sangamo, Sublimity, Sandoz, Takeda, Wildbio. Grants: Altman Research, BMS, Pfizer UK- Research support- Jannsen, Takeda, Medtronic, speaker/advisory fees- Abbvie BMS Celtrion Jannsen Pfizer Takeda Medtronic Roche No specific funding has been received for this study., (Copyright © 2024 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Patients with inflammatory bowel disease (IBD) who undergo proctocolectomy with ileal pouch-anal anastomosis may develop pouchitis. We previously proposed a novel endoscopic classification of pouchitis describing 7 phenotypes with differing outcomes. This study assessed phenotype transitions over time., Methods: We classified pouch findings into 7 main phenotypes: (1) normal, (2) afferent limb (AL) involvement, (3) inlet (IL) involvement, (4) diffuse, (5) focal inflammation of the pouch body, (6) cuffitis, and (7) pouch-related fistulas noted more than 6 months after ileostomy takedown. Among 2 endoscopic phenotypes, the phenotype that was first identified was defined as the primary phenotype, and the phenotype observed later was defined as the subsequent phenotype., Results: We retrospectively reviewed 1359 pouchoscopies from 426 patients (90% preoperative diagnosis of ulcerative colitis). The frequency of primary phenotype was 31% for AL involvement, 42% for IL involvement, 28% for diffuse inflammation, 72% for focal inflammation, 45% for cuffitis, 18% for pouch-related fistulas, and 28% for normal pouch. The most common subsequent phenotype was focal inflammation (64.8%), followed by IL involvement (38.6%), cuffitis (37.8%), AL involvement (25.6%), diffuse inflammation (23.8%), normal pouch (22.8%), and pouch-related fistulas (11.9%). Subsequent diffuse inflammation, pouch-related fistulas, and AL or IL stenoses significantly increased the pouch excision risk. Patients who achieved subsequent normal pouch were less likely to have pouch excision than those who did not (8.1% vs 15.7%; P = .15)., Conclusions: Pouch phenotype and the risk of pouch loss can change over time. In patients with pouch inflammation, subsequent pouch normalization is feasible and associated with favorable outcome., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: We examined corticosteroid use among Israeli patients with Inflammatory Bowel Disease (IBD), focusing on demographic, disease-related, and psychosocial factors. The objective was to contribute to the development of strategies minimizing corticosteroid dependence and improving patient outcomes, given the adverse effects associated with prolonged corticosteroid use., Methods: A comprehensive analysis was conducted on data collected from adult IBD patients attending six gastroenterological outpatient clinics in Israel. The data collected encompassed disease characteristics, demographic information, service level characteristics, social data, and steroid use. Statistical analyses were performed to associate these variables with steroid use., Results: Out of 402 patients, 26 % had been treated with corticosteroids in the previous year, with a majority of these having only one treatment course. Of patients treated with steroids, 57% (n-44) met steroid dependent/excess criteria. Steroid use was more common in patients diagnosed with ulcerative colitis (UC) compared to those with Crohn's disease. Factors such as a diagnosis of UC, male gender, elevated C-reactive protein and fecal calprotectin, and decreased albumin and hemoglobin were associated with steroid use., Conclusion: Corticosteroid use among Israeli IBD patients was associated with disease-related factors and some demographic characteristics. The results highlight the need for continued research to inform strategies aimed at reducing corticosteroid dependence in managing IBD, thereby improving patient outcomes., Competing Interests: Conflict of interest None., (Copyright © 2024 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Goals and Background: Gluten-free diet (GFD) includes a higher intake of sugars and fats. Previous studies have investigated its effect on body mass index (BMI) in celiac disease (CD) patients but had contradictive conclusions. Thus, we conducted a systematic review and meta-analysis examining the effect of GFD on BMI in CD patients., Study: Systematically, we conducted literature research using Medline, Scopus, and Embase, and we identified 1565 potential studies/abstracts. Only studies of patients with CD under a GFD with recorded BMI before and after dietary intervention were included. Subgroup analyses based on study design and BMI categories were performed. We calculated the pooled odds ratios (ORs) and 95% confidence intervals (Cls) for the number of patients in each BMI group according to the World Health Organization (WHO) definitions after GFD using fixed and random effect meta-analysis., Results: The analysis included 10 studies and 38 sub-studies/data sets, which encompassed 2450 patients from 5 countries. We found nonsignificant odds for changing the BMI group (pooled OR 0.972, 95% CI: 0.858-1.101, P=0.65) after GFD. However, looking specifically at BMI subgroups, we found higher odds for BMI category change after GFD in underweight patients (OR 0.588, 95% CI: 0.479-0.723, P <0.001), and overweight patients,25

Background and Aims: Surveillance colonoscopies are crucial for high-risk patients with inflammatory bowel diseases (IBD) to detect colorectal carcinoma (CRC). However, there is no established quality metric for dysplasia detection rate (DDR) in IBD surveillance. This study assessed the DDR in a dedicated surveillance program at a tertiary referral center for IBD., Methods: Consecutive patients with quiescent colitis were enrolled in a cross-sectional study evaluating DDR. High-definition colonoscopy with dye chromoendoscopy (DCE) was performed by a specialized operator. Advanced dysplasia (AD) was defined as low-grade dysplasia ≥ 10 mm, high-grade dysplasia, or colorectal cancer. Risk factors for dysplasia detection were analyzed., Results: In total, 119 patients underwent 151 procedures, identifying 206 lesions, of which 40 dysplastic with seven AD . Per-lesion and per-procedure DDR were 19.4 % and 20.5 %, respectively. The per-procedure AD detection rate (ADDR) was 4.6 %. A Kudo pit pattern of II-V had a sensitivity of 92.5 % for dysplasia detection but a false positive rate of 64.8 % (p < 0.001). Age at diagnosis and at index colonoscopy and past or indefinite dysplasia were associated with per-procedure dysplasia detection., Conclusions: In a real-world setting, a dedicated surveillance program achieved a high DDR. We suggest that optimal DDR in high-risk IBD patients be defined and implemented as a standardized quality measure for surveillance programs., Competing Interests: Conflict of interest H.Y.- reports institutional research grants from Pfizer and the ISF; consulting fees from Abbvie, Janssen, Pfizer, and Takeda; honoraria for lectures from Abbvie, Janssen, Pfizer, Takeda, and BMS; participation in a Data Safety Monitoring Board or Advisory Board from Abbvie, Pfizer, Takeda, and BMS. I.D.: Advisory boards, consultation, speaking and teaching: Abbvie, Abbott, Arena, Athos, BMS/Celgene, Cambridge Healthcare, Celltrion, Genentech/Roche, Gilead, Galapagos, Eli-Lilly, Ferring, Falk Pharma, Food industries organization, Integra Holdings, Iterative Scopes, Janssen, Neopharm, Wild bio, Pfizer, Rafa Laboratories, Sangamo, Sublimity, Takeda J.E.O.: consultation fees from Pfizer, Abbvie, and Takeda; honoraria for lectures from Pfizer, Abbvie, and Takeda I.A.B.: consultation fees from Pfizer, Abbvie, and Takeda; honoraria for lectures from Pfizer, Abbvie, and Takeda, (Copyright © 2023. Published by Elsevier Ltd.)

Background: Real-world data on outcomes of patients with newly diagnosed Crohn's disease (ndCD) is limited. We aimed to assess the achievement of corticosteroid-free clinical remission (CS-free CR) and other therapeutic targets 1 year after diagnosis in a cohort of patients with ndCD treated by a multidisciplinary team (MDT)., Methods: A prospective observational cohort study was conducted on consecutive treatment-naïve adults with ndCD. Patients received management at the treating physician's discretion, along with a tailored nutritional plan provided by an inflammatory bowel disease (IBD)-oriented dietitian. Patients were guided and educated by an IBD nurse, with flexible communication access to the IBD team. Therapeutic targets were assessed at 1 year. Multivariable logistic regression was used to evaluate predictors of CS-free CR., Results: Seventy-six patients (50% female) with a median age of 27 (22-39) years were eligible. Over 75% of patients were assessed by IBD-oriented dietitians and the IBD nurse. Within a median of 4.3 (2.5-6.7) months from diagnosis 60.5% initiated biologics (96% anti- tumor necrosis factor). Dietary intervention was applied to 77.6% of the cohort, either monotherapy (33.9%) or add-on (66.1%). At 1 year, 64.5% of patients achieved sustained CS-free CR, 56.6% biochemical remission, 55.8% endoscopic response, 44.2% endoscopic remission, 30.8% deep remission, and in 39.5% there was an improvement in health-related quality of life (HRQoL). Predictors for CS-free CR were uncomplicated phenotype (B1/P0), lower body mass index, and lower patient-reported outcome 2 scores at diagnosis., Conclusions: In a real-world setting at a tertiary medical center, a cohort of ndCD patients treated by an MDT resulted in favorable 1-year outcomes. Over 60% achieved CS-free CR, along with significant improvements in biomarkers and HRQoL., Competing Interests: H.Y.: reports institutional research grants from Pfizer and the ISF; consulting fees from Abbvie, Janssen, Pfizer, Takeda, and Bristol Myers Squibb; honoraria for lectures from Abbvie, Janssen, Pfizer, and Takeda; participation in a Data Safety Monitoring Board or Advisory Board from Abbvie, Pfizer, Takeda, and Bristol Myers Squibb. I.G.: reports institutional research grants from Pfizer, Gilead, and Boehringer Ingelheim, and research travel grants from the European Crohn’s and Colitis Organization (ECCO) and the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD). J.E.O.: reports institutional research grants from Pfizer. I.D.: received in the last 3 years consultation fee, research grant, or honorarium from Janssen, Pfizer, Abbvie, Takeda, Genentech/Roche, Neopharm, Ferring, Iterative Scopes, Integra Holdings, Eli-Lilly, Falk Pharma, Gilead, Galapagos, Celgene/BMS, Arena, Sublimity, Sangamo, Sandoz, Celltrion, Wilbio, Cambridge Healthcare, Abbott, Food Industries Organization, Altman, Athos. The remaining authors declare that they have no conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn's & Colitis Foundation.)

Vaccines are pivotal for control of the coronavirus disease (COVID-19) pandemic. Patients with inflammatory bowel diseases (IBDs) treated with antitumor necrosis factor (TNF)-α have lower serologic response after two COVID-19 vaccine doses. Data regarding a third vaccine dose are scarce. An Israeli multicenter prospective observational study recruited 319 subjects: 220 with IBD (79 treated with anti-TNFα) and 99 healthy control (HC) participants. All patients received two mRNA-BNT162b2 vaccines (Pfizer/BioNTech), 80% of whom received a third vaccine dose. Evaluation included disease activity, anti-spike (S) and nucleocapsid (N) antibody levels, anti-TNFα drug levels, and adverse events (AEs). All participants showed significant serologic response one month after receiving a third dose. However, three months later, the anti-S levels decreased significantly in patients treated with anti-TNFα compared with the non-anti-TNFα and HC groups. A correlation between serologic response to the third vaccine dose and anti-TNF drug levels was not found. No significant AE or IBD exacerbation was observed. Importantly, lower serologic response after the third vaccine dose predicted infection. A third dose of BNT162b2 is effective and safe in patients with IBD. Lower serologic response predicted infection, even in seropositive subjects. Lower serologic responses and their rapid decline suggest a fourth vaccine dose in this patient population.

Background: Pregnant patients with inflammatory bowel diseases (IBDs) are frequently treated with immunomodulatory agents and may be at increased risk of adverse outcomes, including peripartum infections. We sought to examine the risk for peripartum infections in patients with IBD compared with control subjects and identify potential risk factors associated with peripartum infections in these patients., Methods: This retrospective cohort study compared peripartum infection rates and associated risk factors between pregnant women with and without IBD. The study population included women attending a dedicated joint maternal-fetal medicine and gastroenterology clinic for pregnant women with IBD between 2012 and 2019 at the Rabin Medical Center in Israel, a major referral center for patients with IBD. For each patient, 5 women without IBD were matched according to the newborn's birth date (±2 years), age, parity, and body mass index. Peripartum infection was defined as any 1 of the following: chorioamnionitis, maternal fever (>38°C) detected during labor or postpartum hospitalization, and positive culture taken during the hospitalization., Results: Overall, 195 pregnant women with IBD (72 [37%] with ulcerative colitis, 123 [63%] with Crohn's disease) were matched with 888 control subjects. The mean disease duration was 8.4 ± 7.02 years. IBD therapy, used by 81%, included most frequently 5-aminosalicylic acid (44%) and tumor necrosis factor inhibitors (27%). Peripartum infections were observed in 15 (7.7%) patients and 49 (5.5%) control subjects (P = 1.00). No medication significantly increased the likelihood of peripartum infection. Cesarean delivery was more likely among women with IBD but was not associated with an increased risk of peripartum infection., Conclusions: Peripartum infections were comparable in patients with IBD and control subjects. These reassuring data augment existing knowledge of obstetrical outcomes in IBD patients and contribute to the discussion between caregivers and patients., (© The Author(s) 2022. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Aim: Drug sustainability (DS) is a surrogate marker for treatment efficacy. We aimed to compare the DS of two main biologics used to treat moderate-to-severe ulcerative colitis (UC), infliximab (IFX) and vedolizumab (VDZ), in a real-world setting., Methods: We conducted a retrospective cohort study at a tertiary medical center in Israel. We included patients treated between 1 December 2017 and 1 May 2021, who were followed for up to 300 weeks. DS was defined as corticosteroid-, surgical-, and hospitalization-free treatment., Results: 217 patients with UC were included. VDZ had a significantly longer median DS of 265.6 weeks compared to IFX's 106.5 weeks ( p = 0.001) in treatment-naïve patients, even when adjusting for disease severity (HR 0.55 95 CI 0.3-0.98, p = 0.042). In treatment-experienced patients, DS was comparable between IFX and VDZ ( p = 0.593)., Conclusions: VDZ showed significantly longer DS in treatment-naïve patients with UC compared to IFX, also when adjusted for disease severity. There was no difference in DS between VDZ and IFX in treatment-experienced patients and patients switching from one drug to another. VDZ may be a suitable first-line treatment for biologic-naïve patients with moderate-to-severe UC.

Background: Inflammatory bowel disease (IBD) can have an impact on pregnancy outcomes due to the effect of the disease activity and medication use. This study aimed to evaluate the pregnancy outcomes in IBD patients treated at a multidisciplinary clinic., Methods: This study was a retrospective cohort study including consecutive pregnant patients with IBD having a singleton gestation attending a multidisciplinary clinic between 2012 and 2019. The IBD activity and management throughout gestation were assessed. The pregnancy outcomes included: adverse neonatal and maternal outcomes, mode of delivery, and three integrative outcomes: (1) a favorable pregnancy outcome, (2) a poor pregnancy outcome, and (3) an unfavorable maternal outcome. The IBD pregnant cohort was compared with a cohort of non-IBD pregnant women delivering at the same shift. Multivariable logistic regression was used for risk assessment., Results: Pregnant women with IBD (141) and without (1119) were included. Mean maternal age was 32 [±4] years. Patients with IBD had a higher rate of nulliparity (70/141 (50%) vs. 340/1119 (30%), p < 0.001) and lower BMI (21.42 kg/m 2 (19.18-23.44) vs. 22.48 (20.31-25.59), p = 0.002). All the other characteristics were comparable. Most patients with IBD 124/141 (88%) were in clinical remission at conception; with maintenance therapy in 117/141 patients (83%). A third of the patients, 43/141 (30.5%), were treated with biologics. Exacerbation occurred during pregnancy in 51/141 (36%). The majority of the maternal and neonatal outcomes and all the composite outcomes were comparable between the patients with IBD and the women without IBD. Cesarean delivery was more frequent in patients with IBD (49/141 (34.8%) vs. 270/1119 (24.1%), p = 0.021). IBD was not associated with composite outcomes., Conclusions: In pregnant patients with IBD followed at a multidisciplinary clinic, the pregnancy outcomes were encouraging and comparable to those of the women without IBD.

Background and Aims: With the development of narrow-band imaging (NBI) in the endoscopic evaluation of patients with Barrett's esophagus (BE), the role of random biopsies according to the Seattle protocol (SP) has been questioned. We aim to compare the utility of advanced imaging to SP in patients with BE., Methods: A prospective cohort of patients with proven BE was retrospectively analyzed. All biopsies were reviewed by an expert GI pathologist. Advanced imaging was tandemly used with SP in each endoscopic procedure., Results: A total of 155 out of 340 patients (45.5%) with BE were diagnosed with dysplasia during a median follow-up of 4.7 years (IQR 3.4-6.1 years) and were part of the statistical analysis. A total of 82 patients had a diagnosis of dysplasia at presentation, whereas 84 patients developed dysplasia during follow up. A total of 67 out of 82 patients with dysplasia at presentation (81.7%), and 65 out of 84 patients that were diagnosed with dysplasia during follow-up (77.4%) were diagnosed using SP. In addition, whereas all the events of EAC were diagnosed using targeted biopsies, 57.1% of the events of HGD and 86.3% of LGD were diagnosed using SP., Conclusion: Our findings demonstrate the significance of SP in the detection of low- and high-grade dysplasia in patients with BE. SP should remain the mainstay of endoscopic surveillance in this population.

Introduction: Whether fecal calprotectin (FC) and quality of life (QoL) questionnaires reflect change in disease activity in patients with a J-pouch is unknown., Methods: Patients with acute pouchitis were prospectively treated with a 2-week course of antibiotics. The full Pouchitis Disease Activity Index, FC, and QoL questionnaires were measured at baseline and after antibiotic therapy., Results: Twenty patients were prospectively enrolled. After 2 weeks of antibiotic treatment, the Pouchitis Disease Activity Index decreased from a median of 9 to 5 ( P = 0.007). FC decreased from a median of 661 ug/g to 294 ug/g ( P = 0.02), and QoL questionnaires improved significantly., Discussion: FC and QoL questionnaires reflect real-time changes in inflammatory pouch activity., (Copyright © 2022 by The American College of Gastroenterology.)

Background: Endoscopic-post-operative-recurrence [ePOR] in Crohn's disease [CD] after ileocecal resection [ICR] is a major concern. We aimed to evaluate the effectiveness of early prophylaxis with biologics and to compare anti-tumour necrosis factor [anti-TNF] therapy to vedolizumab [VDZ] and ustekinumab [UST] in a real-world setting., Methods: A retrospective multicentre study of CD-adults after curative ICR on early prophylaxis was undertaken. ePOR was defined as a Rutgeerts score [RS] ≥ i2 or colonic-segmental-SES-CD ≥ 6. Multivariable logistic regression was used to evaluate risk factors, and inverse probability treatment weighting [IPTW] was applied to compare the effectiveness between agents., Results: The study included 297 patients (53.9% males, age at diagnosis 24 years [19-32], age at ICR 34 years [26-43], 18.5% smokers, 27.6% biologic-naïve, 65.7% anti-TNF experienced, 28.6% two or more biologics and 17.2% previous surgery). Overall, 224, 39 and 34 patients received anti-TNF, VDZ or UST, respectively. Patients treated with VDZ and UST were more biologic experienced with higher rates of previous surgery. ePOR rates within 1 year were 41.8%. ePOR rates by treatment groups were: anti-TNF 40.2%, VDZ 33% and UST 61.8%. Risk factors for ePOR at 1 year were: past-infliximab (adjusted odds ratio [adj.OR] = 1.73 [95% confidence interval, CI: 1.01-2.97]), past-adalimumab [adj.OR = 2.32 [95% CI: 1.35-4.01] and surgical aspects. After IPTW, the risk of ePOR within 1 year of VDZ vs anti-TNF or UST vs anti-TNF was comparable (OR = 0.55 [95% CI: 0.25-1.19], OR = 1.86 [95% CI: 0.79-4.38]), respectively., Conclusion: Prevention of ePOR within 1 year after surgery was successful in ~60% of patients. Patients treated with VDZ or UST consisted of a more refractory group. After controlling for confounders, no differences in ePOR risk were seen between anti-TNF prophylaxis and other groups., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Women with inflammatory bowel diseases (IBD) often receive biologics to maintain remission during pregnancy., Aims: To assess maternal and neonatal outcomes in patients with IBD treated with ustekinumab (UST) during pregnancy METHODS: In a multicentre, prospective cohort study, we recruited women with IBD treated with UST during pregnancy between 2019 and 2021. Outcomes were compared among patients treated with UST, anti-tumour necrosis factor α, (anti-TNF) and non-UST, non-anti-TNF therapies. UST-treated patients were matched 1:2 to controls according to age, body mass index and parity. Newborns were followed up to 12 months., Results: We recruited 129 pregnant patients: UST 27; anti-TNF 52; non-UST, non-anti-TNF 50 (thiopurine or mesalazine 30, no therapy 20); Crohn's disease 25 (96.9%). Overall, pregnancy, neonatal and newborn outcomes were satisfactory, with no significant differences among patients treated with UST, anti-TNF and non-UST non-anti-TNF agents for obstetrical maternal complications [UST 3 (11.5%), anti TNF 12 (23.1%), non UST, non-anti-TNF 4 (8.2%), p = 0.095], pre-term delivery [1 (4.3%), 9 (18.4%), 4 (5.7%), p = 0.133], low birth weight [1 (4.2%), 5 (10.2%), 4 (8.3%), p = 0.679], or first year newborn hospitalisation [2 (9.1%), 4 (8.2%), 3 (6.1%), p = 0.885]., Conclusion: Pregnant patients with IBD treated with UST demonstrated favourable pregnancy and neonatal outcomes that were comparable with those in patients treated with anti-TNF or other therapy. Data are reassuring for patients with IBD and their physicians when considering UST during pregnancy., (© 2022 John Wiley & Sons Ltd.)

Introduction: Regulatory agencies supported vaccination of pregnant women with SARS-CoV-2 mRNA vaccines, including patients with IBD. No data exist regarding these vaccines in IBD during pregnancy., Aim: To assess the serologic response to two doses of the mRNA SARS-CoV-2 BNT162b2 vaccine in pregnant women with IBD vaccinated during pregnancy, compared to that of pregnant women without IBD, and non-pregnant women with IBD., Methods: Anti-spike antibody levels were assessed in all women and in cord blood of consenting women., Results: From December 2020 to December 2021, 139 women were assessed: pregnant with IBD-36, pregnant without IBD-61, and not pregnant with IBD-42. Antibodies were assessed in cords of two and nine newborns of women with and without IBD, respectively. Mean gestational ages at administration of the second vaccine doses were 22.0 weeks in IBD and 23.2 weeks in non-IBD, respectively. Mean (SD) duration from the second vaccine dose to serology analysis in pregnant women with IBD, without IBD, and in non-pregnant women with IBD was 10.6 (4.9), 16.4 (6.3), and 4.3 (1.0) weeks, respectively. All women mounted a serologic response. In multivariable analysis, no correlation was found between the specific group and antibody levels. In both pregnancy groups, an inverse correlation between antibody levels and the interval from the second vaccine dose was demonstrated. Cord blood antibody levels exceeded maternal levels in women with and without IBD., Conclusion: All patients with IBD mounted a serologic response. The interval between vaccine administration to serology assessment was the most important factor determining antibody levels. A third vaccine dose should be considered in pregnant women with IBD vaccinated at early stages of pregnancy.

Introduction: We evaluated whether persistent-positive celiac serology is associated with the risk of hypothyroidism., Methods: We extracted a cohort of subjects aged 1-80 years with a positive IgA anti-tissue transglutaminase between January 1, 2008, and December 31, 2012, and a repeat anti-tissue transglutaminase test within 6-36 months from a large population-based electronic medical record database. Based on serology tests, we categorized the pediatric (age &lt;21 years) and adult cohorts into normalized or persistent-positive serology groups. All subjects were followed up for incident diagnosis of hypothyroidism from the last serology date up to December 31, 2017. Hazard ratio (HR) along 95% confidence intervals (CIs) were prepared to evaluate the association of celiac serology group with a diagnosis of hypothyroidism, crude, and adjusted for age, sex, and diagnosis of type 1 diabetes mellitus., Results: Among the pediatric cohort (n = 2,687), during a median follow-up of 64 months (interquartile range 48-80), 2.3% (16/681) of the persistent-positive serology group and 1.0% (20/2,006) of the normalized serology group developed hypothyroidism (HR 2.07 [95% CI 1.07-4.44], adjHR 1.77 [95% CI 0.91-3.46]). The rate among the pediatric cohort with an established diagnosis of celiac disease was 3.4% (10/486) vs 1.0% (5/481), HR 2.83 (0.96-8.32). In the adult cohort (n = 1,286), 4.5% (20/442) of the persistent-positive group and 3.9% (33/811) of the normalized serology group developed hypothyroidism (HR 1.13 [95% CI 0.65-1.97])., Discussion: In this retrospective, age-stratified analysis, we report that persistent-positive serology may be associated with the risk of hypothyroidism among the pediatric population. Prospective cohorts are needed to validate our findings., (Copyright © 2022 by The American College of Gastroenterology.)

Background: Despite significant differences in surgical outcomes between pediatric and adult patients with ulcerative colitis (UC) undergoing colectomy, counseling on pediatric outcomes has largely been guided by data from adults. We compared differences in pouch survival between pediatric and adult patients who underwent total proctocolectomy with ileal pouch-anal anastomosis (IPAA)., Methods: This was a retrospective single-center study of patients with UC treated with IPAA who subsequently underwent pouchoscopy between 1980 and 2019. Data were collected via electronic medical records. We stratified the study population based on age at IPAA. Differences between groups were assessed using t tests and chi-square tests. Kaplan-Meier curves were used to compare survival probabilities. Differences between groups were assessed using a log-rank test., Results: We identified 53 patients with UC who underwent IPAA before 19 years of age and 329 patients with UC who underwent IPAA at or after 19 years of age. Subjects who underwent IPAA as children were more likely to require anti-tumor nerosis factor (TNF) postcolectomy compared with adults (41.5% vs 25.8%; P < .05). Kaplan-Meier estimates revealed that pediatric patients who underwent IPAA in the last 10 years had a 5-year pouch survival probability that was 28% lower than that of those who underwent surgery in the 1990s or 2000s (72% vs 100%; P < .001). Further, children who underwent IPAA and received anti-TNF therapies precolectomy had the most rapid progression to pouch failure when compared with anti-TNF-naive children and with adults who were either exposed or naive precolectomy (P < .05)., Conclusions: There are lower rates of pouch survival for children with UC who underwent IPAA following the uptake of anti-TNF therapy compared with both historical pediatric control subjects and contemporary adults., (© 2022 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background & Aims: Data regarding fecal calprotectin (FC), commonly used for noninvasive monitoring in inflammatory bowel diseases, are scarce in patients with ileal pouch-anal anastomosis (IPAA). We aimed to assess the association between FC levels and pouch inflammation in patients with ulcerative colitis who underwent IPAA., Methods: A cross-sectional study of adults with ulcerative colitis who underwent IPAA with J-pouch formation prospectively followed in a dedicated pouch clinic. Patients had clinical, endoscopic, and histologic assessments within 90 days of FC sampling. Each patient encounter was evaluated separately. Pouchitis was defined as a Pouchitis Disease Activity Score of ≥7 (maximum score: 18)., Results: Overall, 156 patients had 296 encounters that met inclusion criteria. A total of 52% of patients were male, median age at evaluation was 43 (IQR, 35-58) years, and median pouch age was 10 (interquartile range [IQR], 2.5-15) years. Median FC values were significantly lower in patients without compared with those with pouchitis (208 [IQR, 96-478] μg/g vs 550 [IQR, 250-1051] μg/g; P < .0001). Mean FC values increased among patients with higher endoscopic and histologic scores. FC performed better than C-reactive protein as a predictor of pouchitis. FC of >460 μg/g had >80% specificity for predicting significant endoscopic disease (Pouchitis Disease Activity Score endoscopic subscore ≥5), while an FC of <125 μg/g had over 80% specificity in predicting endoscopic remission., Conclusions: FC levels are increased in patients with endoscopic and histologic inflammation of the pouch. FC may be a useful tool in the management of patients following IPAA., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: The endoscopic appearance in patients with "pouchitis" after ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC) can be quite heterogenous. Patients with an endoscopic phenotype resembling Crohn's disease (CD) are at high risk of pouch loss., Aims: We aimed to assess how the histopathology of colectomy specimens predicts endoscopic pouch phenotypes in UC., Methods: We retrospectively assessed pouchoscopies from patients with UC who underwent IPAA and classified pouch findings into 7 main phenotypes: (1) normal, (2) afferent limb involvement, (3) inlet involvement, (4) diffuse, (5) focal inflammation of the pouch body, (6) cuffitis, and (7) pouch with fistulas noted ≥ 6 months from ileostomy takedown. We assessed the clinical and pathological data including deep, focal inflammation, granulomas, and terminal ileal involvement in the colectomy specimens. Logistic regression analysis was performed to identify contributing factors to each phenotype., Results: This study included 1,203 pouchoscopies from 382 patients with UC. On multivariable analysis, deep inflammation was significantly associated with pouch fistulas (Odds ratio 3.27; 95% confidence interval 1.65-6.47; P = 0.0007). Of the 75 patients with deep inflammation, only two patients (2.7%) were diagnosed with CD based on pathology review. Terminal ileal involvement significantly increased the risk of afferent limb involvement (Odds ratio 2.96; 95% confidence interval 1.04-8.47; P = 0.04). There were no significant associations between other microscopic features and phenotypes., Conclusions: We identify histologic features of colectomy specimens in UC that predict subsequent pouch phenotypes. Particularly, deep inflammation in the resected colon was significantly associated with pouch fistulas, a pouch phenotype with poor prognosis., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Patients with inflammatory bowel disease (IBD) treated with anti-tumor-necrosis factor-alpha (TNFα) exhibited lower serologic responses one-month following the second dose of the COVID-19 BNT162b2 vaccine compared to those not treated with anti-TNFα (non-anti-TNFα) or to healthy controls (HCs). We comprehensively analyzed long-term humoral responses, including anti-spike (S) antibodies, serum inhibition, neutralization, cross-reactivity and circulating B cell six months post BNT162b2, in patients with IBD stratified by therapy compared to HCs. Subjects enrolled in a prospective, controlled, multi-center Israeli study received two BNT162b2 doses. Anti-S levels, functional activity, specific B cells, antigen cross-reactivity, anti-nucleocapsid levels, adverse events and IBD disease score were detected longitudinally. In total, 240 subjects, 151 with IBD (94 not treated with anti-TNFα and 57 treated with anti-TNFα) and 89 HCs participated. Six months after vaccination, patients with IBD treated with anti-TNFα had significantly impaired BNT162b2 responses, specifically, more seronegativity, decreased specific circulating B cells and cross-reactivity compared to patients untreated with anti-TNFα. Importantly, all seronegative subjects were patients with IBD; of those, >90% were treated with anti-TNFα. Finally, IBD activity was unaffected by BNT162b2. Altogether these data support the earlier booster dose administration in these patients.

Goal: The aim was to assess whether thrombophilia significantly contributes to the risk of venous thromboembolic events (VTEs) in patients with inflammatory bowel disease (IBD)., Background: Patients with IBD have a high risk of VTE. The underlying mechanism has been only partially defined., Methods: A case-control study in adults with IBD and an episode of VTE (IBD-VTE) were matched and compared with non-IBD patients with a VTE (non-IBD-VTE). The study population was comprised of patients seen in 2 tertiary medical centers in Israel between 2000 and 2013. Characteristics of IBD and risk factors for VTE were retrieved from medical charts, and a comprehensive thrombophilia panel was completed in all patients., Results: Forty-four IBD-VTE cases (27 Crohn's disease) were matched with 127 non-IBD-VTE controls. The majority of VTE had a clear etiology and were considered provoked events. Provoked and unprovoked VTE rates were not different between the 2 groups. Likewise, thrombophilia rates were similar among patients with IBD-VTE and controls (40.9% vs. 53.5%, respectively, P=0.14). However, among patients with unprovoked VTE, thrombophilia rates were significantly lower in the IBD-VTE group compared with controls (42.1% vs. 70.7%, respectively, P=0.03). Among patients with IBD-VTE, an unprovoked event, and negative thrombophilia, 77% had active inflammation at the time of VTE., Conclusion: Thrombophilia rates are similar among patients with IBD-VTE and controls but are less common among patients with unprovoked IBD-VTE. This finding suggests that either inflammation or other novel pathways drive VTE in patients with IBD., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Goal: The aim was to assess topics of interest and concerns among patients with inflammatory bowel diseases (IBD) who are active online., Background: Social media (SM) networks are a major communication tool for patients with IBD and health care professionals., Patients and Methods: We performed an anonymized investigation of SM networks for IBD patients; I-a thematic analysis of patients' posts, II-an online survey advertised through Facebook and other popular SM networks throughout November 2019., Results: Analyzing 2133 posts (2014 to 2019) revealed 18 topics of interest. The online survey was completed by 534 respondents [63%-Crohn's disease, 56%-female, median age-38 years (interquartile range: 28.7 to 51.0)]. Most respondents (70%) were followed in referral centers, and 45% were receiving biological therapy. Respondents reported high satisfaction with IBD care and health care provider professionalism. The top 5 topics of interest were diet, lifestyle, complementary and alternative medicine, diagnostic test interpretation, and specialist referrals and reviews. Cluster analysis demonstrated that gender, income, and education level were associated with specific interest and concerns., Conclusion: Patients' activity on SM is independent of their satisfaction with formal IBD care and rather reflects an ongoing need for information and support. These needs may be addressed both in clinical settings and through online tools., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Crohn's disease (CD) and ulcerative colitis (UC) are chronic, immune-mediated inflammatory bowel diseases (IBD) affecting millions of people worldwide. IBD therapies, designed for continuous immune suppression, often render patients more susceptible to infections. The effect of the immune suppression on the risk of coronavirus disease-19 (COVID-19) is not fully determined yet., Objective: To describe COVID-19 characteristics and outcomes and to evaluate the association between IBD phenotypes, infection outcomes and immunomodulatory therapies., Methods: In this multi-center study, we prospectively followed IBD patients with proven COVID-19. De-identified data from medical charts were collected including age, gender, IBD type, IBD clinical activity, IBD treatments, comorbidities, symptoms and outcomes of COVID-19. A multivariable regression model was used to examine the effect of immunosuppressant drugs on the risk of infection by COVID-19 and the outcomes., Results: Of 144 IBD patients, 104 (72%) were CD and 40 (28%) were UC. Mean age was 32.2 ± 12.6 years. No mortalities were reported. In total, 94 patients (65.3%) received biologic therapy. Of them, 51 (54%) at escalated doses, 10 (11%) in combination with immunomodulators and 9 (10%) with concomitant corticosteroids. Disease location, behavior and activity did not correlate with the severity of COVID-19. Biologics as monotherapy or with immunomodulators or corticosteroids were not associated with more severe infection. On the contrary, patients receiving biologics had significantly milder infection course ( p = 0.001) and were less likely to be hospitalized ( p = 0.001). Treatment was postponed in 34.7% of patients until recovery from COVID-19, without consequent exacerbation., Conclusion: We did not witness aggravated COVID-19 outcomes in patients with IBD. Patients treated with biologics had a favorable outcome.

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., Competing Interests: Conflict of interest H. Yanai: reports institutional research grants from Pfizer; consulting fees from Abbvie, Ferring, Janssen, Neopharm Ltd., Pfizer, Takeda; honoraria for lectures from Abbvie, Janssen, Pfizer, Takeda; participation on a Data Safety Monitoring Board or Advisory Board from Abbvie, Neopharm Ltd., Pfizer, Takeda. I. Avni Biron: Consulting fees from Takeda; honoraria for lectures from Abbvie, Janssen, Pfizer, Takeda, Neopharm Ltd; Clinical R&D team employee, Medtronic. I.Dotan: Consultation: Arena, Athos therapeutics, Gilead, Cambridge Healthcare, Wild bio, Food industries organization, Integra Holdings, Iterative Scopes. Speakers Bureau/lectures: Janssen, Abbvie, Takeda, Pfizer, Genentech/Roche, Arena, Neopharm, Celltrion, Rafa Laboratories, Ferring, Falk Pharma, Nestle, Celgene/BMS, Abbott. DSMB/advisory boards: SPARE consortium Janssen, Abbvie, Takeda, Pfizer, Genentech/Roche, Arena, Neopharm, Gilead, Galapagos, Celltrion, Sublimity, Wild bio, Athos therapeutics, Food industries organization, Celgene/BMS, Abbott, Sublimity, Sandoz. A. Bar-Gil Shitrit: Research grants from Takeda and Janssen, Consulting and honoraria for lectures from Takeda, Janssen' Abbvie, Pfizer and Neopharm. U. Kopylov: Research grants from Janssen, Takeda Medtronic, Consulting and honoraria- Abbvie, BMS, Janssen, MSD Medtronic, Takeda, Pfizer R. Weisshof: Consulting and honoraria for lectures from Takeda, Janssen, Abbvie. Advisory board fees from Janssen and AMAG Pharmaceuticals N. Maharshak: speaking and/ or consulting fees from Pfizer, Takeda, Janssen, Ferring, BiomX, BMS, Nestle and grant support from Takeda, Janssen, Abbott, Pfizer, BMS, Corundum Innovation Ltd E. Israeli: Research grants from Abbvie; Consulting and honoraria for lectures from Takeda, Janssen, Abbvie, Pfizer, Ferring Teva and BMS. I. Goren: Institutional research grant from Pfizer JE Ollech: Institutional research grant from Pfizer B. Koslowsky, A. Levartovsky, N. Aviv Cohen, D. Hovel, T. Naftali, Y. Snir, H. Banai-Eran, Y. Broitman, T. Sharar-Fischler -None., (Copyright © 2021. Published by Elsevier Ltd.)

Background & Aim: Patients with inflammatory bowel diseases (IBD), specifically those treated with anti-tumor necrosis factor (TNF)α biologics, are at high risk for vaccine-preventable infections. Their ability to mount adequate vaccine responses is unclear. The aim of the study was to assess serologic responses to messenger RNA-Coronavirus Disease 2019 vaccine, and safety profile, in patients with IBD stratified according to therapy, compared with healthy controls (HCs)., Methods: Prospective, controlled, multicenter Israeli study. Subjects enrolled received 2 BNT162b2 (Pfizer/BioNTech) doses. Anti-spike antibody levels and functional activity, anti-TNFα levels and adverse events (AEs) were detected longitudinally., Results: Overall, 258 subjects: 185 IBD (67 treated with anti-TNFα, 118 non-anti-TNFα), and 73 HCs. After the first vaccine dose, all HCs were seropositive, whereas ∼7% of patients with IBD, regardless of treatment, remained seronegative. After the second dose, all subjects were seropositive, however anti-spike levels were significantly lower in anti-TNFα treated compared with non-anti-TNFα treated patients, and HCs (both P < .001). Neutralizing and inhibitory functions were both lower in anti-TNFα treated compared with non-anti-TNFα treated patients, and HCs (P < .03; P < .0001, respectively). Anti-TNFα drug levels and vaccine responses did not affect anti-spike levels. Infection rate (∼2%) and AEs were comparable in all groups. IBD activity was unaffected by BNT162b2., Conclusions: In this prospective study in patients with IBD stratified according to treatment, all patients mounted serologic response to 2 doses of BNT162b2; however, its magnitude was significantly lower in patients treated with anti-TNFα, regardless of administration timing and drug levels. Vaccine was safe. As vaccine serologic response longevity in this group may be limited, vaccine booster dose should be considered., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Pouchitis is a common complication of ileal pouch-anal anastomosis (IPAA) in patients with ulcerative colitis who have undergone colectomy. Pouchitis has been considered a single entity despite a broad array of clinical and endoscopic patterns. We developed a novel classification system based on the pattern of inflammation observed in pouches and evaluated the contributing factors and prognosis of each phenotype., Methods: We identified 426 patients (384 with ulcerative colitis) treated with proctocolectomy and IPAA who subsequently underwent pouchoscopies at the University of Chicago between June 1997 and December 2019. We retrospectively reviewed 1359 pouchoscopies and classified them into 7 main pouch phenotypes: (1) normal, (2) afferent limb involvement, (3) inlet involvement, (4) diffuse, (5) focal inflammation of the pouch body, (6) cuffitis, and (7) pouch with fistulas noted 6 months after ileostomy takedown. Logistic regression analysis was used to assess factors contributing to each phenotype. Pouch survival was estimated by the log-rank test and the Cox proportional hazards model., Results: Significant contributing factors for afferent limb involvement were a body mass index of 25 or higher and hand-sewn anastomosis, for inlet involvement the significant contributing factor was male sex; for diffuse inflammation the significant contributing factors were extensive colitis and preoperative use of anti-tumor necrosis factor drugs, for cuffitis the significant contributing factors were stapled anastomosis and preoperative Clostridioides difficile infection. Inlet stenosis, diffuse inflammation, and cuffitis significantly increased the risk of pouch excision. Diffuse inflammation was associated independently with pouch excision (hazard ratio, 2.69; 95% CI, 1.34-5.41; P = .005)., Conclusions: We describe 7 unique IPAA phenotypes with different contributing factors and outcomes, and propose a new classification system for pouch management and future interventional studies., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Evidence regarding the risk of immunogenicity in patients with inflammatory bowel disease (IBD) who switched anti-tumor necrosis factor alpha (anti-TNFα) therapies to a subsequent anti-TNFα (either infliximab or adalimumab) is conflicting. We aimed to assess the risk of consecutive immunogenicity to anti-TNFα in a large cohort of patients., Methods: This was a multicenter retrospective study. Medical records of adult and pediatric IBD switchers who had pharmacokinetic data for both agents between 2014 and 2020 were retrieved. Data including age, sex, disease type, duration of therapies, and concomitant use of immunomodulators (IMMs) were recorded., Results: Overall, 164 patients were included [52% female; 88% Crohn's disease; mean age = 24.4 ± 14.6 years; 108 (66%) switched from infliximab to adalimumab and 56 (34%) vice versa]; 120 (73.1%) patients switched due to an immunogenic failure. Among patients switching therapy from infliximab to adalimumab due to an immunogenic failure immunogenicity to infliximab was significantly associated with consecutive immunogenicity to adalimumab ( p = 0.026). Forthy four out of 120 patients (36.6%) with an immunogenic failure to the first anti-TNFα started an IMM with the second anti-TNFα. This combination with IMM was not associated with reduction of consecutive immunogenicity ( p = 0.31), but it was associated with longer drug retention ( p = 0.007). Multivariate analysis demonstrated that older age at second anti-TNFα, adjusted to the chronology of therapy and sex, was associated with increased immunogenicity to the second anti-TNFα., Conclusion: Patients with IBD who switch from infliximab to adalimumab following an immunogenic failure are at increased risk for consecutive immunogenicity to adalimumab. IMM use after a switch prolongs drug retention., Competing Interests: Conflict of interest statement: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: H.Y.: Consultation and lectures fees from Abbvie, Janssen, Neopharm Ltd., Pfizer, and Takeda, and research grants from Pfizer. R.S.: Research grants from Abbvie. A.A.: Consultation and lectures fees from Abbvie and Takeda, and research grants from Abbvie and Janssen. M.M. and S.A. have no financial conflicts of interest to declare. B.U.: Consultation and lectures fees from Abbvie, Takeda, Janssen, and Neopharm Ltd. U.K.: Consulting fees from Abbvie, Jannsen, Takeda, MSD, Pfizer, and Medtronic; honoraria for lectures from Abbvie, Jannsen, Takeda, MSD, Pfizer, and Medtronic; leadership or fiduciary role from Takeda; and research grants from Takeda, Jannsen, and Medtronic. I.G.: Research grants from Pfizer, and travel grants from ECCO and IOIBD. I.D.: Institutional research grants from Altman and Pfizer; consulting fees from Arena, Gilead, Cambridge Healthcare, Wild bio, Food industries organization, and Integra Holdings; honoraria for lectures from Janssen, Abbvie, Takeda, Pfizer, Genentech/Roche, Arena, Neopharm Ltd., Celltrion, Rafa Laboratories, Ferring, Falk Pharma, Nestle, Celgene/BMS, and Abbott; and participation on a Data Safety Monitoring Board or Advisory Board from spare consortium Janssen, Abbvie, Takeda, Pfizer, Genentech/Roche, Arena, Neopharm Ltd., Gilead, Galapagos, Celltrion, Sublimity, Wild bio, Athos therapeutics, Food industries organization, Celgene/BMS, and Abbott. TSF, IAB, JEO and TTP report no conflicts of interest, (© The Author(s), 2022.)

Background: Patients with Crohn's disease (CD) frequently undergo abdominopelvic computed tomography (APCT) in the emergency department (ED). It's essential to diagnose clinically actionable findings (CAF) as they may need immediate intervention, frequently surgical. However, repeated APCT's includes increased ionizing radiation exposure. Guidance regarding APCT performance is mostly clinical and empiric., Aims: We used a machine learning (ML) approach for predicting CAF on APCT in the ED., Methods: We performed a retrospective cohort study of patients with CD who presented to the ED and underwent APCT. CAF were defined as bowel obstruction, perforation, intra-abdominal abscess or complicated fistula. ML was used to predict the probability of having CAF on APCT, using routine clinical variables., Results: Of 101 admissions included, 44 (43.5%) had CAF on APCT. ML successfully identified patients at low (NPV 91.6%, CI-95% 90.6-92.5) and high (PPV 92.8%, CI-95%, 92.3-93.2) risk for CAF (AUROC = 0.774), using beats-per-minute, mean arterial pressure, neutrophil-to-lymphocyte ratio and sex. This allowed the construction of a risk stratification scheme according to patients' probability for CAF on APCT., Conclusion: We present a novel artificial intelligence-based approach, utilizing readily available clinical variables to better select patients with CD in the ED for APCT. This might reduce the number of APCTs performed, avoiding related hazards while ensuring high-risk patients undergo APCT., (Copyright © 2021. Published by Elsevier Ltd.)

Background and Aims: Skin eruptions are prevalent among patients with inflammatory bowel diseases (IBD), often associated with therapies and frequently leading to dermatological consults and treatment interruptions. We aimed to assess the impact of joint shared decision-making in a multidisciplinary (MDT) IBD-DERMA clinic., Methods: This retrospective cohort study assessed a consecutive group of patients with IBD who were referred for consultation in an MDT clinic at a tertiary referral center in Israel., Results: Over 1 year, 118 patients were evaluated in the MDT-IBD-DERMA clinic: 68 (57.6%) males; age - 35.2 ± 13.5 years, disease duration - 7.1 (interquartile range: 3.7-13.9) years; Crohn's disease - 94/118 (79.6%). Skin eruption induced by an anti-tumor necrosis factor (TNF) were the most common diagnoses [46/118 (39%)], including psoriasiform dermatitis (PD) - 31/46 (67.4%) and inflammatory alopecia (IA) - 15/46 (32.6%). Of these, 18 patients (39.1%) continued the anti-TNF agent concomitantly with a topical or systemic anti-inflammatory agent to control the eruption. The remaining 28 patients (60.9%) discontinued the anti-TNF, of whom 16/28 (57.1%) switched to ustekinumab. These strategies effectively treated the majority [38/46 (82.6%)] of patients. Continuation of the anti-TNF was possible in a significantly higher proportion of patients with PD: 12/31 (38.7%) than only one in the IA group, p  = 0.035. There was a higher switch to ustekinumab among the IA 7/15 (46.6%) compared with the PD 7/31 (22.6%) group, P  = .09. Following IBD-DERMA advised intervention, IBD deteriorated in 9/4 6(19.5%) patients, 5/9 on ustekinumab (PD versus IA, P  = NS)., Conclusion: Shared decision-making in an integrated IBD-DERMA clinic allowed successful control of skin eruptions while preserving control of the underlying IBD in more than 80% of cases. Patients with IA profited from a switch to ustekinumab., Competing Interests: Conflict of interest statement: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Henit Yanai: reports institutional research grants from Pfizer; consulting fees from Abbvie, Ferring, Janssen, Neopharm Ltd., Pfizer, Takeda; honoraria for lectures from Abbvie, Janssen, Pfizer, Takeda; participation on a Data Safety Monitoring Board or Advisory Board from Abbvie, Neopharm Ltd., Pfizer, Takeda. Hadar Amir Barak: none. Jacob E Ollech: none. Irit Avni Biron: none. Idan Goren: reports institutional research grants from Pfizer. Yifat Snir: none. Hagar Banai Eran: none. Yelena Broitman: none. Maya Aharoni Golan: none. Elena Didkovsky: none. Iris Amitay-Laish: none. Ayelet Ollech: none. Emmilia Hodak: none relevant. Iris Dotan: research grants from Altman Research, Pfizer; Advisory board/consulting fees: Pfizer, Janssen, Abbvie, Takeda, Genentech/Roche, Arena, Neopharm, Gilead, Galapagos, Celltrion, Rafa Laboratories, Ferring, DSM, Cambridge Healthcare, Sublimity, Sangamo, Wild Biotech, Food industries organization, Integra Holdings, Celgene/BMS, Abbott, 89 Bio, Alimentiv; Speakers Bureau: Roche/Genentech, Falk Pharma, Abbvie, Janssen, Pfizer, Takeda Neopharm, Celltrion, Ferring, Nestle, Celgene/BMS. Lev Pavlovsky has served as an investigator for Abbvie, Coherus, Novartis Pharmaceuticals Corporation, Janssen Biotech, Eli Lilly, Bristol Myers Squibb and as an advisor, consultant, and/or invited lecturer for Abbvie, Janssen Biotech, Novartis Pharmaceuticals Corporation, Pfizer Inc., Dexcel Pharma, Eli Lilly, and Boehringer Ingelheim., (© The Author(s), 2021.)

Data regarding the management and outcomes of acute severe ulcerative colitis (ASUC) in pregnant patients is sparse, consisting mainly of case reports. 1-3 We report on the largest cohort of pregnant patients hospitalized with ASUC and performed a systematic review of the medical literature., (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background and Aim: Approximately half of patients with Crohn's disease (CD) who have surgery will experience clinical recurrence within 10 years of their surgery. This study aimed to assess the postoperative outcomes according to disease location and validated the simple endoscopic score for CD (SES-CD) to predict disease-related outcomes., Methods: We retrospectively assessed medical records of CD patients who underwent ileocolonoscopy within 12 months after surgery at the University of Chicago between 2005 and 2016. We defined patients with postoperative colonic inflammation at the first postoperative ileocolonoscopy or had Montreal classification L2 as colon-dominant disease and patients without colonic involvement or who had L1 as small intestine (SI)-dominant disease. The outcomes included clinical and surgical recurrence., Results: Among 207 CD patients, 51 (24.6%) and 156 (75.4%) patients had colon-dominant and SI-dominant disease, respectively. Patients with colon-dominant disease had a greater risk of postoperative clinical recurrence compared with those with SI-dominant disease (P = 0.018). Colon-dominant disease was a risk of earlier surgical recurrence compared with SI-dominant disease, although there were no significant differences in the recurrence-free survivals. SES-CD > 2 at the first postoperative ileocolonoscopy was a significant risk of clinical recurrence on log-rank test (P < 0.001) and Cox proportional hazards model (hazard ratio = 2.25; 95% confidence interval = 1.14-4.47; P = 0.020). An SES-CD of 1 was an appropriate cut-off to predict the clinical recurrence of SI-dominant disease, but a higher SES-CD cut-off value of 5 was required for colon-dominant disease., Conclusions: We demonstrated that SES-CD predicts postoperative clinical recurrence of CD, regardless of disease location., (© 2021 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Interruptions in infliximab therapy are associated with the development of antibodies to infliximab (ATI), infusion reactions (IRs), and loss of response. Despite these challenges, recent observational studies suggest that reinitiating infliximab after a drug holiday can be safe and effective. We assessed the utility of our protocol for restarting infliximab using early serum infliximab and ATI measurements., Methods: A retrospective cohort study of patients restarted on infliximab after at least a 6-month drug holiday. The cohort was divided into 2 groups: a "therapeutic drug monitoring (TDM) group," those who had serum infliximab and ATI measured 1-3 weeks after first reinduction dose, and a "non-TDM group." Outcomes included results of TDM, occurrence of immediate IR (IIR) and delayed hypersensitivity reactions, and medication persistence at 14 weeks and 1 year., Results: About 76 patients were included: 49 in the TDM group and 27 in the non-TDM group. Of 76, 67 (88%) patients tolerated the first reinduction dose without IR. Formation of ATI was seen in 17 of 49 (35%) patients and was associated with longer drug holidays. Most did not experience IR during the entire therapy course-in 26 of 32 (81%) without ATI and 20 of 27 (74%) in the non-TDM group. Infliximab persistence at 14 weeks and 1 year was 76% and 57% for the cohort, respectively., Conclusion: Infliximab can be safely and effectively restarted after a drug holiday. We suggest performing TDM with a drug-tolerant assay 1-3 weeks after the first reinduction infusion as a means to identify patients at risk for severe IIR at the second dose., (© The Author(s) 2021. Published by Oxford University Press on behalf of Crohn's & Colitis Foundation.)

Background & Aims: A subset of patients with Crohn's disease (CD) do not respond to ustekinumab at the standard dose of 90 mg every 8 weeks. Little is known about the efficacy of shortening the interval between doses., Methods: We performed a retrospective study to determine the effectiveness of ustekinumab dose interval shortening, collecting data from 506 patients with CD who received subcutaneous ustekinumab 90 mg every 8 weeks at a single center. We obtained data from 110 patients who initially received subcutaneous ustekinumab 90 mg every 8 weeks and then had their interval shortened to every 4 weeks. Harvey Bradshaw Index (HBI) scores before and after the dose interval shortening was available for 78 patients in the cohort (71%), levels of C-reactive protein (CRP) for 60 patients (55%), and levels of fecal calprotectin for 8 patients (7%)., Results: Following dose interval shortening, the patients' median HBI decreased from 4.5 to 3 (P = .002), the median level of CRP decreased from 8 mg/L to 3 mg/L (P = .031), and median level of fecal calprotectin decreased from 378 μg/g to 157 μg/g (P = .57). Among patients who had an HBI >4, a level of CRP ≥5mg/dL, a level of fecal calprotectin >250ug/g, or endoscopic evidence for disease activity before dose interval shortening, after the dose interval was shortened, 28% achieved clinical remission (an HBI score ≤4), 22% had a normal level of CRP (<5 mg/dL), 50% had reduced levels of fecal calprotectin, and 36% achieved endoscopic remission., Conclusions: Shortening the ustekinumab 90 mg dose interval to 4 weeks for patients with CD who did not respond to doses every 8 weeks improved clinical and biological indices of disease activity. Patients who lose response to the standard dose of ustekinumab might benefit from dose interval shortening, which was effective and safe., (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Introduction: In this study, we evaluate the efficacy and safety of the biosimilar infliximab, CT-P13, in the treatment of inpatients with severe steroid-refractory colitis., Methods: A retrospective cohort study of adult colitis patients (UC or isolated Crohn's colitis) admitted to the University of Chicago inflammatory bowel disease inpatient service between January 2018 and December 2018 for management of severe colitis refractory to IV steroids who received CT-P13 were included in the study. Patients diagnosed with active small bowel Crohn's disease were excluded. CT-P13 was given as a single infusion of 5 to 10 mg/kg. A comprehensive review of their electronic medical records was performed, and demographic, clinical, laboratory, and endoscopic data were extracted. The primary endpoint was colectomy-free survival., Results: Twenty-one patients with severe steroid-resistant colitis were included. Twelve patients had ulcerative colitis, seven patients had a diagnosis of indeterminate colitis, and two patients had a diagnosis of Crohn's colitis. The median age was 32.2 years. The median disease duration was 4.3 years, and the median follow-up time was 5.9 months. Patients had a median CRP of 23. All patients had moderate to severe disease on endoscopy. Colectomy-free survival was 76% at 3 months and 70% at 6 months. No severe adverse events were reported in this patient cohort., Conclusion: A significant proportion of patients with severe colitis failing IV steroids responded to induction therapy with CT-P13. Colectomy-free survival rates were similar to previous randomized trials using originator infliximab as induction therapy in severe steroid-refractory colitis.

The natural history of ulcerative colitis (UC) follows a relapsing and remitting course of inflammation and is accompanied by associated mucosal injury and historically, microscopic features of chronicity that were the sine qua non for the diagnosis. 1 As goals for the management of UC have evolved to include objectively measured endoscopic improvement of the mucosa, there also has been a move to include histological endpoints in assessment of disease activity. 2,3 However, there remain a number of unanswered questions about histology in UC and this is not yet a specific treatment goal. 4 ., (Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.)

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., (© 2019 John Wiley & Sons Ltd.)

Background: Chronic antibiotic-refractory pouchitis (CARP) occurs in up to 15% of patients with ulcerative colitis (UC) following proctocolectomy with ileal pouch-anal anastomosis (IPAA)., Aim: To investigate the effectiveness of ustekinumab in the treatment of CARP., Methods: This was a retrospective single-center study of UC patients with an IPAA, who subsequently developed CARP and received ustekinumab with standard Crohn's disease (CD) dosing between 2016 and 2018. Patients with CD of the pouch were excluded. Demographic, clinical, and endoscopic data were collected. Outcomes included a change in the endoscopic subscore of the Pouchitis Disease Activity Index (PDAI), change in the ulcerated surface area, clinical response, and the number of bowel movements per 24 h., Results: Twenty-four patients with CARP were included for analysis. Median follow-up time was 12.9 months (IQR 7.9-16). Twelve patients (50%) had a clinical response with the median number of bowel movements within 24 h decreasing from 8 (IQR, 5-12) to 6 (IQR, 5-8) P = 0.002. Thirteen patients had pouchoscopies available post-ustekinumab treatment. In these patients, the median endoscopic subscore of the PDAI decreased from 5 (IQR, 3-6) to 4 (IQR, 2-5), P = 0.016. Likewise, among these thirteen patients, nine (69%) had an ulcerated surface area > 10% before ustekinumab treatment; after treatment with ustekinumab, only four patients (31%) still had an ulcerated surface area of > 10%., Conclusions: This is the largest study of ustekinumab treatment for patients with chronic antibiotic-refractory pouchitis. We found that ustekinumab therapy led to the improvement in clinical and endoscopic endpoints.

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 and Aims: Options for medical management of patients with acute severe colitis [ASC] failing intravenous (i.v.) steroids are limited and include rescue therapy with either infliximab or ciclosporin. In patients failing infliximab, second-line rescue therapy with ciclosporin is an alternative. The aim of this study was to investigate the efficacy and safety of ciclosporin in patients with steroid-refractory ASC failing first-line rescue therapy with infliximab., Methods: This is a retrospective, tertiary centre study undertaken from 2010 to 2017. Included were patients hospitalized for ASC and treated with i.v. ciclosporin after failing i.v. steroids and infliximab within the previous 2 months. Time to colectomy, clinical response, and occurrence of adverse events were analysed., Results: Forty patients with steroid-resistant ASC were included. Patients were followed for a median of 13 months (interquartile range [IQR] 5-32 months). Colectomy-free survival was 65%, 59.4%, and 41.8% at 1 month, 3 months and 1 year, respectively. Sixty percent of patients [24/40] achieved clinical remission at a median of 2 weeks [IQR 1-3 weeks]. Infliximab levels before ciclosporin infusion were available for 26 patients [median level 17.5 mg/mL, IQR 8-34 mg/mL] and were not associated with adverse events. Sixteen patients [40%] experienced adverse events after ciclosporin treatment, but none resulted in drug discontinuation., Conclusions: In patients with i.v. steroid-refractory ASC who failed infliximab therapy, second-line rescue therapy with ciclosporin was shown to be effective and safe. This is the largest patient cohort to receive ciclosporin as second-line rescue therapy for ASC. We believe that ciclosporin may be offered to selected patients prior to referral for colectomy., (Copyright © 2019 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background and Aims: Recurrence of Crohn's disease after surgical resection and primary anastomosis is an important clinical challenge. Previous studies have demonstrated the benefit of imidazole antibiotics, but have been limited by adverse events and medication intolerance. We evaluated whether administration of low-dose metronidazole [250 mg three times per day] for 3 months reduces endoscopic postoperative recurrence rates., Methods: We performed a retrospective cohort study of patients with Crohn's disease who underwent ileal resection with a primary anastomosis and subsequently received care at our center. We compared the cases who received low-dose metronidazole for 3 months with control patients who did not receive this therapy. Data collected included demographics, risk factors for recurrence, and medications before and after surgery. The primary end point was the number of patients with ≥i2 [Rutgeerts] endoscopic recurrence by 12 months. Variables found to be predictive in univariate analysis at p < 0.10 were introduced in the Cox model for multivariate analysis., Results: In all, 70 patients with Crohn's disease [35 cases and 35 controls] met inclusion criteria. Risk factors for Crohn's recurrence were similar between groups. The number of patients with ≥i2 endoscopic recurrence within 12 months following ileal resection was significantly lower in the metronidazole group [7 of 35 patients; 20%] compared with the number in the control group [19 of 35 patients; 54.3%] [p = 0.0058]. Eight participants [22.9%] in the metronidazole group experienced adverse events, and 3 of these patients [8.6%] discontinued the therapy., Conclusion: Low-dose metronidazole reduces endoscopic recurrence of Crohn's disease postoperatively and is well tolerated. This intervention should be considered as a therapy option following ileocolonic resection., (Copyright © 2019 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background and Aims: It is standard of care to perform ileocolonoscopy within a year of ileocolonic resection for Crohn's disease (CD) and to guide management decisions based on the Rutgeert score (RS). The modified RS subdivides i2 into lesions confined to the anastomosis (i2a) or >5 aphthous lesions in the neoterminal ileum (i2b). There is uncertainty, however, if i2a lesions incur an increased risk of disease recurrence. The primary aim of this study was to compare the rates of endoscopic progression between i2a and i2b when compared with i0-i1., Methods: This was a retrospective, single-center study including patients with CD who had an ileocolonoscopy ≤12 months after ileocolonic resection with primary anastomosis and who had >1 year of documented clinical follow-up after the index endoscopic evaluation. All consecutive eligible patients between 2004 and 2014 were included in the study. Demographic, disease, and treatment data were collected. Patients with i3 or i4 at index colonoscopy were excluded from further analyses. Outcomes included endoscopic progression and recurrent surgery. For patients with RS of i0 to i2, endoscopic progression was predefined as progression of the RS in subsequent colonoscopies to i3 or i4. Recurrent surgical interventions were defined as re-resection or stricturoplasty of the previous ileocolonic anastomosis., Results: Two hundred seven CD patients (median age, 36 years [interquartile range, 26-48]) had an ileocolonoscopy ≤12 months after ileocolonic resection. At index colonoscopy, 95 patients (45.9%) had an RS of i0, 31 (14.9%) i1, 40 (19.3%) i2a, 25 (12.1%) i2b, 10 (4.8%) i3, and 6 (2.9%) i4. One hundred ninety-one patients had an RS of i0 to i2 and were included in the analyses for recurrent surgery. One hundred forty-nine patients had a second endoscopic evaluation and were included in the analysis for the primary outcome of endoscopic disease progression. Kaplan-Meier analyses were performed and found the hazard ratio (HR) of endoscopic progression to be significantly higher with i2b lesions when compared with i0 or i1 (HR, 6.22; 95% confidence interval [CI], 2.38-16.2; P = .0008). Patients with i2a did not have significantly higher rates of endoscopic progression when compared with i0 or i1 (HR, 2.30; 95% CI, .80-6.66; P = .12). Likewise, patients with i2b lesions had higher risk of needing recurrent surgery when compared with i0 or i1 (HR, 3.64; 95% CI, 1.10-12.1; P = .034), whereas patients with i2a lesions were not found to have a significantly elevated risk of recurrent surgery (HR, 1.43; 95% CI, .35-5.77; P = .62)., Conclusion: Endoscopic lesions limited to the ileocolonic anastomosis (RS i2a) in patients with CD undergoing colonoscopy within 1 year of their resection were not associated with a significantly higher rate of progression to more severe disease, whereas those in the neoileum (RS i2b) were. Prospective studies are needed to confirm these findings., (Copyright © 2019 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)