Eran Zittan

INTRODUCTION: The Toronto Inflammatory Bowel Disease (IBD) Global Endoscopic Reporting (TIGER) score was developed to provide 1 endoscopic scoring index for patients with both Crohn's disease (CD) and ulcerative colitis (UC). The goal of this study was to assess the predictive validity the TIGER score for daily-life disease burden (IBD Disk) and disease complications. METHODS: A prospective 12-month study was conducted in 1 tertiary IBD center. Baseline colonoscopy was performed. Moderate-to-severe mucosal involvement was defined as a TIGER score ≥100, Simple Endoscopic Score for CD >6, Mayo Endoscopic Score >1, and was used as a predictor for clinical outcomes. At each visit, IBD Disk questionnaires, disease complications, hospitalizations, surgeries, and medications were documented. RESULTS: A total of 107 adults, 52 with CD and 55 with UC, were included. Patients with a baseline TIGER score ≥100 had a significantly higher prevalence of an IBD Disk score ≥40 after the 12-month follow-up period despite receiving advanced therapy (33.9% vs 7.8%, P < 0.001). There were significantly more patients with a baseline TIGER score ≥100 who experienced at least 1 hospitalization (39.3% vs 2.0%, P < 0.001), underwent surgery (14.3% vs 0.0%, P < 0.005), had IBD-related complications (41.1% vs 9.8%, P < 0.001), and required steroids (67.9% vs 5.9%, P < 0.001) or advanced therapy (85.7% vs 7.8%, P < 0.001). Similar significant results were obtained with Simple Endoscopic Score for CD and Mayo Endoscopic Score as predictors of outcomes over the 12 months. DISCUSSION: The TIGER score is a simple endoscopic score for patients with CD and UC with an adequate predictive validity for worse clinical outcomes while having noninferiority to the current best-referenced endoscopic scores.

Background and Aims: The Toronto IBD Global Endoscopic Reporting (TIGER) score is a single endoscopic scoring index for both patients with Crohn’s disease (CD) and ulcerative colitis (UC). The goal of this study was to assess the direct relationship between TIGER scores and fecal calprotectin (FC) and C-reactive protein (CRP) after 12 months. Methods: A prospective 12-month study conducted in 1 tertiary IBD center. Baseline colonoscopy was performed. Moderate-to-severe mucosal involvement was defined as a TIGER score ≥ 100, Simple Endoscopic Score for Crohn’s disease ≥ 6, Mayo Endoscopic Score > 1. FC and CRP levels were documented at each visit. Baseline TIGER, SES-CD, and MES were utilized as a predictor for FC and CRP levels after 12 months. Results: The study population included 107 adults, 52 with CD and 55 with UC. A baseline TIGER score ≥ 100 had a sensitivity and specificity of 0.964 and 0.941, respectively, at predicting a patient having an FC level ≥ 800 μg/g and/or a CRP level ≥ 1.0 mg/dL at 12-month follow-up. A baseline TIGER score ≥ 100 was associated with increased likelihood of having FC > 100 μg/g (P < .001), and ≥ 800 μg/g (P < .001) after 12 months, despite receiving advanced therapy, after the 12-month follow-up period. Similar trends were observed with the SES-CD and MES. Conclusions: The TIGER score is a simple endoscopic score that can be used for both CD and UC that has been shown to have both construct validity with inflammatory marker and noninferiority to the current best-referenced endoscopic scores over a 12-month follow-up period. Future studies should begin incorporating TIGER as a measure of clinical response to interventions and therapeutics.

Objectives: Stress is associated with inflammatory bowel disease (IBD) development and exacerbation. We evaluated the impact of the war in Gaza on Israeli IBD patients and related barriers to IBD care.Methods: Adult IBD patients were blindly enrolled to complete a patient‐reported‐outcome electronic questionnaire assessing symptoms, hospitalizations, medications, psychosocial factors, economic issues, and adherence to therapy during wartime.Results: Overall, 526 participants completed the questionnaire, 67% with CD and 33% with UC. Fifty one percent had moderate–severe IBD patients. Compared to central residents, residents of peripheral regions described a higher need for financial support as their main missing aspect in IBD coping (26% vs. 17%), had increased financial difficulties attributed to wartime that led them to skip therapy (21% vs. 9%), and reported increased rates of requiring financial support to purchase biological medications (13% vs. 3%). Compared to mild patients, moderate–severe patients reported significantly more disease aggravations (47% vs. 23%), hospitalizations (16% vs. 2%), greater need for financial support as their main missing aspect in IBD coping (31% vs. 11%), increased financial difficulties attributed to wartime that led them to skip medical therapy (32% vs. 3%), increased rates of missing IBD medical therapy owing to wartime‐related stress (34% vs. 11%), and increased daily cannabis use (21% vs. 9%).Conclusions: Periphery‐residents with IBD experience more financial difficulties, hospitalizations, and disease exacerbation during wartime. Efforts should be taken to minimize disparities in medical care availability and accessibility, with special emphasis on moderate–severe patients who are more prone to disease aggravations.

Several fecal microbial transplantation (FMT) approaches for ulcerative colitis (UC) have been investigated with conflicting results. We have recently published the clinical outcomes from the CRAFT-UC Trial using FMT with the UC Exclusion Diet (UCED), compared with FMT alone. Here we aimed to compare the two FMT strategies in terms of microbial profile and function. Subjects recruited to the CRAFT-UC study with available pre- and post-intervention fecal samples were included. Donors received diet conditioning for 14 days based on the UCED principles. Group-1 received single FMT by colonoscopy (Day 1) and enemas (Days 2 and 14) without donors' dietary conditioning (N=11). Group-2 received FMT but with donors' dietary pre-conditioning and UCED for the patients (N=10). Fecal samples were assessed by DNA shotgun metagenomic sequencing. Following diet conditioning, donors had depletion in metabolic pathways involved in sulfur-containing amino acids biosynthesis. Only Group-2 showed significant shifts towards the donors’ microbial composition (ADONIS: R2=0.15, p=0.008) and significant increased Eubacterium_sp_AF228LB post-intervention (β-coefficient 2.66, 95%CI 2.1-3.3, q<0.05) which was inversely correlated with fecal calprotectin (rho=-0.52, p=0.035). Moreover, pathways involved in gut inflammation and barrier function including branched chain amino acids were enriched post intervention in Group-2 and were significantly inversely correlated with fecal calprotectin. FMT from diet conditioned donors followed by the UCED led to microbial alterations associated with favorable microbial profile which correlated with decreased fecal calprotectin. Our findings support further exploration of additive benefit of dietary intervention for both donors and patients undergoing FMT as a potential treatment of UC.

Autoimmune pancreatitis [AIP] is rarely associated with inflammatory bowel disease [IBD]. The long-term outcomes of AIP and IBD in patients with coexisting AIP–IBD and predictors of complicated AIP course have rarely been reported. An ECCO COllaborative Network For Exceptionally Rare case reports project [ECCO-CONFER] collected cases of AIP diagnosed in patients with IBD. Complicated AIP was defined as a composite of endocrine and/or exocrine pancreatic insufficiency, and/or pancreatic cancer. We explored factors associated with complicated AIP in IBD. We included 96 patients [53% males, 79% ulcerative colitis, 72% type 2 AIP, age at AIP diagnosis 35 ± 16 years]. The majority of Crohn’s disease [CD] cases [78%] had colonic/ileocolonic involvement. In 59%, IBD preceded AIP diagnosis, whereas 18% were diagnosed simultaneously. Advanced therapy to control IBD was used in 61% and 17% underwent IBD-related surgery. In total, 82% of patients were treated with steroids for AIP, the majority of whom [91%] responded to a single course of treatment. During a mean follow-up of 7 years, AIP complications occurred in 25/96 [26%] individuals. In a multivariate model, older age at AIP diagnosis was associated with a complicated AIP course (odds ratio [OR] = 1.05, p = 0.008), whereas family history of IBD [OR = 0.1, p = 0.03], and CD diagnosis [OR = 0.2, p = 0.04] decreased the risk of AIP complications. No IBD- or AIP-related deaths occurred. In this large international cohort of patients with concomitant AIP–IBD, most patients have type 2 AIP and colonic IBD. AIP course is relatively benign and long-term outcomes are favourable, but one-quarter develop pancreatic complications. Age, familial history of IBD, and CD may predict uncomplicated AIP course.

Summary: Background: Curcumin and QingDai (QD, Indigo) have been shown to be effective for treating active ulcerative colitis (UC).Aim: To evaluate the real‐world experience with the Curcumin–QingDai (CurQD) herbal combination to induce remission in active UC.Methods: A retrospec‑tive multicentre adult cohort study from five tertiary academic centres (2018–2022). Active UC was defined as a Simple Clinical Colitis Activity Index (SCCAI) ≥ 3. Patients were induced by CurQD. The primary outcome was clinical remission at weeks 8–12, defined as SCCAI ≤2 and a decrease ≥3 points from baseline. Secondary outcomes were clinical response (SCCAI decrease ≥3 points), corticosteroid‐free remission, faecal calprotectin (FC) response (reduction ≥50%), FC normalisation (FC ≤100 μg/g for patients with FC ≥300 μg/g at baseline), and safety. All outcomes were analysed for patients who were maintaining stable treatment.Results: Eighty‐eight patients were included; 50% were biologics/small molecules experienced, and 36.5% received ≥2 biologics/small molecules. Clinical remission was achieved in 41 (46.5%), and clinical response in 53 (60.2%). Median SCCAI decreased from 7 (IQR:5–9) to 2 (IQR:1–3); p < 0.0001. Of the 26 patients on corticosteroids at baseline, seven achieved corticosteroid‐free remission. Among 43 biologics/small molecules experienced patients, clinical remission was achieved in 39.5% and clinical response in 58.1%. FC normalisation and response were achieved in 17/29 and 27/33, respectively. Median FC decreased from 1000 μg/g (IQR:392–2772) at baseline to 75 μg/g (IQR:12–136) at the end of inductions (n = 30 patients with paired samples); p < 0.0001. No overt safety signals emerged.Conclusion: In this real‐world cohort, CurQD effectively induced clinical and biomarker remission in patients with active UC, including patients who were biologics/small molecules experienced.

To the Editors: Recent data indicate that 50% of inflammatory bowel disease (IBD) patients have used and 75% plan to use complementary medicine approaches for their IBD.¹ Moreover, some thought leaders have recognized the need to carefully weigh possible candidates for clinical adoption,² but data on IBD experts’ attitudes toward complementary medicine are still scant. We recently conducted a survey among Israeli IBD experts, exploring the current shift of attitudes toward such therapies. A questionnaire was compiled and sent by email to a representative sample of leading expert members of the National Israeli IBD Society. Overall, 40 IBD experts were approached and 25 (62.5%) responded. Respondents were all Board certified and experienced gastroenterologists. On a 7-point Likert-type standard scale (1 = not at all, 7 = very much), 76% of respondents thought that a dialogue between integrative and conventional medicine practitioners is very important (a score of 6 or 7) and 72% thought that IBD patients are very interested to learn about integrative medicine treatment options. A total of 50% of respondents reported that they frequently and 37.5% reported that they occasionally refer their patients to some form of integrative medicine. Among several popular complementary medicine compounds or regimens ( Figure 1), a combination of curcumin and Qing Dai (indigo naturalis) (CurQD) was perceived as the most evidence-based and beneficial IBD treatment.^3-6 This survey among leading national experts in IBD suggests that physicians are increasingly cognizant of patients’ interest in exploring integrative medicine therapy options. These findings also reinforce the message by Sudhakar et al² and the conclusions of a European Crohn’s and Colitis Organization⁷ topical review in calling for more cross-talk and holistic integration between well-evidenced complementary therapies and mainstay medical interventions for our IBD patients.

Summary: 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 pregnancyMethods: 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.

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.

INTRODUCTION: We investigated whether early adalimumab drug levels (ADL) at week 4 predicted biological remission at week 24. METHODS: In a prospective study, we assessed clinical and biological remission at weeks 0, 4, 12, and 24 after induction of adalimumab in 33 patients with Crohn's disease. Disease activity was determined by the Harvey-Bradshaw Index, ileocolonoscopy reports, cross-sectional imaging, C-reactive protein (CRP), and fecal calprotectin (FC) levels. Clinical remission was defined as Harvey-Bradshaw Index <5. Biological remission was defined as a combination of FC < 200 μg/g and CRP 13.9 μg/mL) were significantly associated with biological remission at week 24.