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Background: Recruitment for randomized controlled trials [RCTs] in inflammatory bowel diseases [IBD] has substantially dropped over time. This study aimed to assess reasons why IBD patients are not included in sponsored multicentre phase IIb-III RCTs., Methods: All IOIBD members [n = 58] were invited to participate. We divided barriers to participation as follows: [1] reasons patients with active IBD were not deemed appropriate for an RCT; [2] reasons qualified patients did not wish to participate; and [3] reasons for screen failure [SF] in patients agreeing to participate. We assess these in a 4-week prospective study including, consecutively, all patients with symptomatic disease for whom a treatment change was required. In addition, we performed a 6-month retrospective study to further evaluate reasons for SF., Results: A total of 106 patients (60 male [56.6%], 63 Crohn's disease [CD] [59.4%]), from ten centres across the world, were included in the prospective study. An RCT has not been proposed to 65 of them [mainly due to eligibility criteria]. Of the 41 patients to whom an RCT was offered, eight refused [mainly due to reluctance to receive placebo] and 28 agreed to participate. Among these 28 patients, five failed their screening and 23 were finally included in an RCT. A total of 107 patients (61 male [57%], 67 CD [62.6%]), from 13 centres worldwide, were included in our retrospective study of SFs. The main reason was insufficient disease activity., Conclusion: This first multicentre study analysing reasons for non-enrolment in IBD RCTs shows that we lose patients at each step. Eligibility criteria, the risk of placebo assignment, and insufficient disease activity were part of the main barriers., (© The Author(s) 2023. 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 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: 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 Aims: Patients with inflammatory bowel disease [IBD] are often affected during their reproductive years and may have many perinatal queries that require the comprehensive perspectives of a multidisciplinary team [MDT]. The purpose of this topical review is to assess the scientific evidence and provide expert opinion related to nutritional, psychological and supportive care of women and their infants throughout the prenatal, antenatal and infant periods., Methods: A consensus expert panel of a paediatrician, gastroenterologists, nurses and dietitians was convened by the European Crohn's and Colitis Organisation. This panel critically reviewed literature related to the non-medical management of patients with IBD during preconception, pregnancy, the postnatal period and the first years of the infant's life. Statements were developed using an e-Delphi process over two rounds and were confirmed when ≥80% of experts agreed with the statements., Results: A total of 19 current practice positions were developed that cover the preconception period, pregnancy and lactation, and early-life exposures associated with risk of IBD. Development of the infant microbiome and its role in the immune system and topics including nutritional optimization, psychological support and education relating to early life were reviewed., Conclusions: Patients with IBD have unique nutritional and psychosocial needs that may affect fertility and pregnancy outcomes. The early-life environment of infants born to parents with IBD may be associated with subsequent development of IBD in offspring. An MDT is the optimal setting to support and counsel patients throughout the perinatal period., (© 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.)

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.)

Objectives: Despite encouraging data gathered in inflammatory bowel diseases (IBD) patients, Vedolizumabs' (VDZ) safety profile in pregnancy is not established., Design: Data of 330 consecutive pregnancies with IBD was prospectively collected., Results: Women with IBD were treated with: VDZ (n = 24), anti-tumor necrosis factors (n = 82) or conventional therapy (n = 224). Gravidity and parity were similar among the 3 groups. The VDZ group was comprised mostly of Crohn's disease patients who were all not naïve to biological treatment. They had significantly higher conception rates during active disease (P < 0.05), with fewer flares during pregnancy., Discussion: Although further study is needed, VDZ appears of low risk during pregnancy.

Introduction: Several real-world experience (RWE) studies with vedolizumab (VDZ) for induction of remission in inflammatory bowel diseases (IBD) have been published; however, long-term RWE data is scarce., Aims: To describe the effectiveness and safety of VDZ in maintenance treatment of IBD., Methods: A multicenter retrospective national study. The primary outcome of was clinical response at week 52; main secondary aims included clinical remission at week 52, rates of secondary loss of response and treatment discontinuation., Results: We included 193 (133-CD; 60-UC) patients from 9 Israeli IBD centers. At week 52, response was observed in 62/133 (46.7%) CD patients, including 28 (21%) in clinical remission; 71 (53.3%) discontinued treatment or did not respond. For UC, response at week 52 was observed in 27/60 (45%), including 20 (33%) in clinical remission; 33 (55%) discontinued treatment or did not respond. Secondary non-response by week 52 occurred in 19.4% and 23.5% of week 14 responders in CD and UC, respectively. Week 14 response was associated with treatment continuation at week 52: no predictors of secondary loss of response were identified., Summary: VDZ is safe and effective for maintenance of response and remission in IBD; week 14 response is positively associated with long-term response in both UC and CD., (Copyright © 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Vedolizumab (VDZ) is an anti-integrin monoclonal antibody effective in ulcerative colitis (UC) and Crohn's disease (CD). The aim of this study was to examine the "real world" efficacy and safety of VDZ in a large national patient cohort., Methods: Patients with inflammatory bowel disease treated with VDZ were prospectively followed for 14 weeks. Patients who completed the induction protocol (week 0/2/6/14) or discontinued the treatment before week 14 for adverse events (AEs) or primary nonresponse were included. The primary outcome was induction of clinical remission at week 14; secondary outcomes included clinical response and corticosteroid-free clinical remission., Results: A total of 204 patients (CD-130, UC-69, inflammatory bowel disease-unclassified-5) from 8 centers in Israel were included. Fifteen (7.4%) of the patients were anti-tumor necrosis factor naive and 46 (35.4%) had a previous surgery. For patients with CD, 69/130 (53.1%) responded to treatment; 45 (34.6%) achieved clinical remission; and 38 (29.2%) achieved corticosteroid-free remission at week 14. Fourteen (10.7%) patients discontinued VDZ before week 14 due to primary nonresponse or AEs. For UC, 32/74 (43.2%) responded to treatment; 20 (28.4%) achieved clinical remission, and 18 (24.3%) achieved corticosteroid-free remission at week 14. Fifteen (20.3%) patients with UC did not complete the induction due to primary nonresponse or AEs. AEs were reported by 29 (14.2%) patients (CD and UC combined), most common being nasopharyngitis and skin eruptions., Conclusions: In a large real-world Israeli cohort of anti-tumor necrosis factor-experienced patients with inflammatory bowel disease, VDZ was effective and safe in induction of clinical remission and steroid-free clinical remission.

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. [ABSTRACT FROM AUTHOR]

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/m2 (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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]