Irit Avni-Biron

INTRODUCTION: The gut microbiome in Crohn's disease (CD) shows variability and conflicting associations with disease activity. We aimed to assess microbial and clinical trajectories in newly diagnosed CD (ndCD) over 1 year. METHODS: This prospective longitudinal inception cohort study followed treatment-naive patients with ndCD for 1 year. The primary outcome was sustained corticosteroid-free clinical remission (CSFR) after 1 year. Paired fecal samples were collected at diagnosis and 1 year later, analyzed using bacterial 16S rRNA gene high-throughput sequencing. Microbial composition changes were compared between baseline and 1-year follow-up and between biologics-treated and conservatively managed patients. Fecal samples from healthy volunteers served as controls. RESULTS: Seventy-three patients participated; 64.4% achieved sustained CSFR after 1 year. During follow-up, 60.3% had moderate-to-severe disease activity and received biologics (95.5% anti-tumor necrosis factor), whereas 39.7% were managed conservatively. Significant microbial improvements, including increased Shannon diversity and decreased microbial dysbiosis index, were observed only in patients achieving sustained CSFR (both P < 0.001). Biologic-treated patients had more disrupted baseline microbiome composition than conservatively managed ones (Shannon, P = 0.04; microbial dysbiosis index, P = 0.03); they showed significant microbial improvement regardless of clinical success, shifting toward a healthier microbiome profile. Changes in clinical outcomes over 1 year correlated with microbial alterations. DISCUSSION: Over 1 year, treatment-naive patients with ndCD showed microbial improvements paralleling clinical outcomes, with shifts toward a healthier state. Biologic therapy enhanced microbial profiles, likely due to greater baseline disruption in these patients. These findings suggest that the microbiome is a marker of inflammation and a modifiable factor in CD management.

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: 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.

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 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/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.

Background & 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 Dec 1st, 2017, and May 1st, 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). Conclusion: 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.

Aims Isolated complicated perianal disease (cPD) might be the sole representation of Crohn’s disease (CD). We aimed to evaluate the impact of small bowel capsule endoscopy (SBCE) as a diagnostic tool for CD in this population. Methods A multicenter, retrospective cohort study from three tertiary centers. Patients with cPD who had a negative workup for CD (Ileocolonoscopy and cross-sectional imaging) and underwent evaluation with SBCE were included. Demographics, biomarkers, and the Lewis inflammatory score (LS) were recorded and analyzed. A LS≥135 was considered a positive SBCE. Results Ninety-one patients were included: 65 males (71.4%), mean age 40 (14) years, median duration of cPD 25.13 months (12.53-66.1). SBCE was positive in 24 patients (26.37%). Median LS was 675 (222-1518). Fecal calprotectin (FC) positively correlated with LS (r=0.81; p<0.0001): patients with a positive vs. negative SBCE had a significantly higher mean FC level (255 [389] vs 97[180], p=0.02), ([Fig. 1]). Correspondingly, a FC level ≥ 300 mg/kg had a specificity of 90% for a positive SBCE, while a cutoff of FC level <100 mg/kg or <50 mg/kg had a sensitivity of only 40% or 50% to rule out small bowel CD, respectively. Conclusions SBCE was positive in over a quarter of patients with cPD and a negative workup for CD. FC levels correlated with the degree of inflammation defined by the LS. However, the sensitivity of low FC to rule out CD was low. These results suggest that SBCE is an essential diagnostic tool for patients with cPD even after negative workup. Article published online: 14 April 2023 © 2023. European Society of Gastrointestinal Endoscopy. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

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.

LINKED CONTENT: This article is linked to Avni‐Biron et al papers. To view these articles, visit https://doi.org/10.1111/apt.17224 and https://doi.org/10.1111/apt.17260