Greater adherence to the Mediterranean Dietary Approaches to Stop Hypertension Intervention for Neurodegenerative Delay (MIND) diet is associated with lower risk of inflammatory bowel disease: a prospective cohort study.

Background: The Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet is emerging as a promising candidate for preventive measures against inflammatory bowel disease (IBD), though there is currently no direct evidence from population-based studies. This study aims to bridge the gap in understanding of the association of the MIND diet with IBD risk. Methods: We utilized data from 187 490 participants in the UK Biobank who provided dietary information and were free of IBD at baseline. Dietary information was obtained using a validated web-based 24-hour dietary recall questionnaire. A MIND diet score was evaluated based on the intake of ten beneficial and five unhealthy food groups and the scores were further grouped into tertiles. The outcome of interest was incident IBD, Crohn's disease (CD), and ulcerative colitis (UC). Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard models adjusted for demographic characteristics, lifestyle factors, cancer history, and other dietary factors. Mediation analyses were performed to evaluate the role of systemic inflammation and metabolic disorders represented by the integrated biomarkers in the MIND diet-IBD association. Results: After a mean follow-up of 10.7 years, we documented 825 incident IBD cases (250 CD and 575 UC). The average age of the participants was 56.2 years, of which 55.0% were females. We found that greater adherence to the MIND diet, represented by a higher diet score, was associated with a lower risk of IBD (HRcomparing extreme tertiles 0.74, 95% CI 0.62-0.90, p = 0.002; p for trend = 0.005), CD (HR 0.66, 95% CI 0.47-0.94, p = 0.022; p for trend = 0.023), and UC (HR 0.78, 95% CI 0.62-0.98, p = 0.031; p for trend = 0.022). The associations were partially mediated by metabolic and inflammation status (mediation proportion: 5.5-15.9%). Conclusion: We found higher adherence to the MIND diet was associated with a lower risk of IBD, and that inflammatory and metabolic conditions may play an important role in the underlying mechanistic pathways.

Dietary quercetin intake is associated with lower ulcerative colitis risk but not Crohn's disease in a prospective cohort study and in vivo experiments.

Objectives: Previous preclinical evidence indicates a protective role of quercetin against inflammatory bowel disease (IBD). However, there is no evidence from human populations, resulting in knowledge gaps regarding the role of quercetin in the IBD development. We aimed to prospectively evaluate the associations between dietary quercetin intake and IBD in humans and in vivo animal models. Methods: We included 187 709 IBD-free participants from the UK Biobank. Dietary information was collected using validated 24-hour dietary recalls and the quercetin intake was estimated based on national nutrient databases. Incident IBD was ascertained via inpatient and primary care data. Cox proportional hazard models were used to estimate the multi-variable adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). Experiments were conducted in two chemical-induced (dextran sulfate sodium salt and trinitro-benzene-sulfonic acid) mouse models orally pretreated with quercetin (CAS number: 117-39-5) solution to evaluate the effects of quercetin at physiological levels. Results: After a mean follow-up of 9.7 years, we documented 863 incident IBD. Compared to participants with the lowest quintile intake of quercetin, those in the highest quintiles were associated with a lower risk of IBD (aHR 0.76, 95% CI 0.60-0.95; P-trend = 0.004) and ulcerative colitis (aHR 0.69, 95% CI 0.53-0.91; P-trend = 0.001), but not Crohn's disease (aHR 0.95, 95% CI 0.62-1.45; P-trend = 0.765). Mouse models showed that pretreatment with quercetin could attenuate the chemically induced colitis. Conclusions: Higher quercetin intake was associated with a lower risk of IBD, especially UC. The protective role of quercetin is promising in humans and warrants further investigation into downstream mechanisms.

Clinical Update on the Prevention and Management of Postoperative Crohn's Disease Recurrence.

PURPOSE OF REVIEW: Despite advances in therapeutics, a significant portion of patients with Crohn's disease still require surgical management. In this article, we present updates to the natural history, prognostication and postoperative monitoring, and novel therapeutics in the prevention and treatment of postoperative Crohn's disease recurrence. RECENT FINDINGS: Clinical risk factors have been associated with higher rates of postoperative recurrence (POR), and in recent studies demonstrate an increased cumulative risk with presence of additional risk factors. Additional novel clinical, histologic, and "-omic" risk factors for recurrence have recently been elucidated, including the role of the mesentery on recurrence and perioperative intraabdominal septic complications. High-risk patients benefit most from medical prophylaxis, including anti-TNF with or without immunomodulator therapy to prevent recurrence. New biologics such as vedolizumab and ustekinumab have emerging evidence in the use of prophylaxis, especially with recent REPREVIO trial data. Non-invasive disease monitoring, such as cross-sectional enterography, intestinal ultrasound, and fecal calprotectin, have been validated against ileocolonoscopy. Recent advances in the prediction, prevention, and monitoring algorithms of postoperative Crohn's disease may be leading to a reduction in postoperative recurrence. Ongoing trials will help determine optimal monitoring and management strategies for this at-risk population.

Prophylactic Versus Endoscopy-driven Treatment of Crohn's Postoperative Recurrence: A Retrospective, Multicentric, European Study [PORCSE Study].

BACKGROUND AND AIMS: No consensus exists on optimal strategy to prevent postoperative recurrence [POR] after ileocaecal resection [ICR] for Crohn's disease [CD]. We compared early medical prophylaxis versus expectant management with treatment driven by findings at elective endoscopy 6-12 months after ICR. METHODS: A retrospective, multicentric, observational study was performed. CD patients undergoing first ICR were assigned to Cohort 1 if a biologic or immunomodulator was [re]started prophylactically after ICR, or to Cohort 2 if no postoperative prophylaxis was given and treatment was started as reaction to elective endoscopic findings. Primary endpoint was rate of endoscopic POR [Rutgeerts >i1]. Secondary endpoints were severe endoscopic POR [Rutgeerts i3/i4], clinical POR, surgical POR, and treatment burden during follow-up. RESULTS: Of 346 included patients, 47.4% received prophylactic postoperative treatment [proactive/Cohort 1] and 52.6% did not [reactive/Cohort 2]. Endoscopic POR [Rutgeerts >i1] rate was significantly higher in Cohort 2 [41.5% vs 53.8%, OR 1.81, p = 0.039] at endoscopy 6-12 months after surgery. No significant difference in severe endoscopic POR was found [OR 1.29, p = 0.517]. Cohort 2 had significantly higher clinical POR rates [17.7% vs 35.7%, OR 3.05, p = 0.002] and numerically higher surgical recurrence rates [6.7% vs 13.2%, OR 2.59, p = 0.051]. Cox proportional hazards regression analysis showed no significant difference in time to surgical POR of proactive versus expectant/reactive approach [HR 2.50, p = 0.057]. Quasi-Poisson regression revealed a significantly lower treatment burden for immunomodulator use in Cohort 2 [mean ratio 0.53, p = 0.002], but no difference in burden of biologics or combination treatment. CONCLUSIONS: The PORCSE study showed lower rates of endoscopic POR with early postoperative medical treatment compared with expectant management after first ileocaecal resection for Crohn's disease.

Azathioprine Plus Exclusive Enteral Nutrition Versus Azathioprine Monotherapy for the Prevention of Postoperative Recurrence in Patients with Crohn's Disease: An Open-Label, Single-Centre, Randomized Controlled Trial.

BACKGROUND: Azathioprine [AZA] effectively prevents postoperative endoscopic recurrence [ER] in Crohn's disease [CD]. However, the efficacy of AZA emerges after 3 months. Exclusive enteral nutrition [EEN] can maintain remission in CD. The present trial investigates whether AZA plus postoperative 3-month EEN is superior to AZA alone in preventing ER of CD. METHODS: In total, 84 high-risk CD patients undergoing intestinal resection received AZA alone or AZA plus 3 months of EEN [AZA + EEN] postoperatively. The primary endpoint was the rate of ER at 12 months. Secondary endpoints included the rate of ER at 3 months, clinical recurrence [CR], CD activity index [CDAI] scores, faecal calprotectin [FC], and C-reactive protein [CRP]. Quality of life was assessed using Short Form-36 [SF-36] and the Inflammatory Bowel Disease Questionnaire [IBDQ]. RESULTS: Patients in the AZA + EEN group exhibited significantly lower rates of ER compared to the AZA group at both 12 months (33.3% [13/39] vs 63.2% [24/38], P = 0.009) and 3 months (8.6% [3/35] vs 28.1% [9/32], P = 0.037) post-surgery. The rates of CR between the two groups at 3 and 12 months were similar. CDAI scores, FC, albumin level, and CRP were all comparable between the two groups. Quality of life was significantly higher in the AZA group than in the AZA + EEN group at 3 months but became comparable from 5 to 12 months postoperatively. CONCLUSION: In high-risk CD patients, combining AZA with postoperative 3-month EEN reduces 1-year ER but may temporarily impact quality of life. Further large-scale, long-term studies are warranted. TRIAL NUMBER: NCT05214430.

Real-World Surgical and Endoscopic Recurrence Based on Risk Profiles and Prophylaxis Utilization in Postoperative Crohn's Disease.

BACKGROUND & AIMS: Preoperative risk stratification may help guide prophylactic biologic utilization for the prevention of postoperative Crohn's disease (CD) recurrence; however, there are limited data exploring and validating proposed clinical risk factors. We aimed to explore the preoperative clinical risk profiles, quantify individual risk factors, and assess the impact of biologic prophylaxis on postoperative recurrence risk in a real-world cohort. METHODS: In this multicenter retrospective analysis, patients with CD who underwent ileocolonic resection (ICR) from 2009 to 2020 were identified. High-risk (active smoking, ≥2 prior surgeries, penetrating disease, and/or perianal disease) and low-risk (nonsmokers and age >50 y) features were used to stratify patients. We assessed the risk of endoscopic (Rutgeert score, ≥i2b) and surgical recurrence by risk strata and biologic prophylaxis (≤90 days postoperatively) with logistic and time-to-event analyses. RESULTS: A total of 1404 adult CD patients who underwent ICR were included. Of the high-risk factors, 2 or more ICRs (odds ratio [OR], 1.71; 95% CI, 1.13-2.57), active smoking (OR, 1.73; 95% CI, 1.17-2.53), penetrating disease (OR, 1.41; 95% CI, 1.02-1.94), and history of perianal disease alone (OR, 1.99; 95% CI, 1.42-2.79) were associated with surgical but not endoscopic recurrence. Surgical recurrence was lower in high-risk patients receiving prophylaxis vs not (10.2% vs 16.7%; P = .02), and endoscopic recurrence was lower in those receiving prophylaxis irrespective of risk strata (high-risk, 28.1% vs 37.4%; P = .03; and low-risk, 21.1% vs 38.3%; P = .002). CONCLUSIONS: Clinical risk factors accurately illustrate patients at risk for surgical recurrence, but have limited utility in predicting endoscopic recurrence. Biologic prophylaxis may be of benefit irrespective of risk stratification and future studies should assess this.

Comparative Persistence of Non-tumor Necrosis Factor (TNF) vs. TNF Antagonists for Post-operative Prophylaxis in Crohn's Disease (CD).

BACKGROUND: The comparative safety and effectiveness of available biologics for post-operative prophylaxis in Crohn's disease (CD) is uncertain. Drug persistence may serve as a real-world proxy for tolerability and effectiveness. We evaluated the comparative persistence of non-TNF and TNF antagonists for post-operative prophylaxis and their comparative effectiveness for preventing early endoscopic post-operative recurrence (POR). METHODS: We conducted a single-center, retrospective study of surgically naïve CD subjects undergoing ileocecal or small bowel resection between 1/1/2000 and 12/31/2021 and prescribed a biologic for post-operative prophylaxis. We compared the risk of prophylaxis failure (requiring recurrent surgery or discontinuation of therapy due to persistent POR despite optimized drug level or dose escalation, immunogenicity, and/or adverse event) and early endoscopic POR (Rutgeert's score ≥ i2 within 15 months postoperatively) between non-TNF and TNF antagonist prophylaxis using Cox proportional hazard and logistic regression, respectively, adjusting for demographic and disease characteristics. RESULTS: The study included 291 subjects (81% TNF antagonists). After multivariable adjustment, non-TNF antagonist prophylaxis was associated with a significantly lower risk of prophylaxis failure than TNF antagonists (hazard ratio 0.26; 95% confidence interval (CI) [0.13-0.53]). Prophylaxis with non-TNF and TNF antagonists had similar risk of early endoscopic POR (odds ratio 0.66; 95% CI [0.32-1.36]). Stratifying the non-TNF antagonists by anti-integrin and anti-IL12/23 yielded similar results. CONCLUSION: In a cohort of surgically naïve CD subjects prescribed a biologic for post-operative prophylaxis, non-TNF antagonists had greater persistence than TNF antagonists with similar risk for early endoscopic POR. If confirmed by large, prospective studies, these findings can inform post-operative management strategies in CD.

Early life exposure to broccoli sprouts confers stronger protection against enterocolitis development in an immunological mouse model of inflammatory bowel disease.

IMPORTANCE: To our knowledge, IL-10-KO mice have not previously been used to investigate the interactions of host, microbiota, and broccoli, broccoli sprouts, or broccoli bioactives in resolving symptoms of CD. We showed that a diet containing 10% raw broccoli sprouts increased the plasma concentration of the anti-inflammatory compound sulforaphane and protected mice to varying degrees against disease symptoms, including weight loss or stagnation, fecal blood, and diarrhea. Younger mice responded more strongly to the diet, further reducing symptoms, as well as increased gut bacterial richness, increased bacterial community similarity to each other, and more location-specific communities than older mice on the diet intervention. Crohn's disease disrupts the lives of patients and requires people to alter dietary and lifestyle habits to manage symptoms. The current medical treatment is expensive with significant side effects, and a dietary intervention represents an affordable, accessible, and simple strategy to reduce the burden of symptoms.

Higher dietary fibre intake is associated with lower risk of inflammatory bowel disease: prospective cohort study.

BACKGROUND: Limited prospective studies that have examined the association of dietary fibre with IBD have provided inconsistent evidence. AIM: To examine any associations between dietary fibre intake and subsequent incidence of IBD, Crohn's disease (CD) and ulcerative colitis (UC) METHODS: We conducted a prospective cohort study of 470,669 participants from the UK Biobank and estimated dietary fibre intake from a valid food frequency questionnaire at baseline. Incident IBD was ascertained from primary care data and inpatient data. Cox proportional hazard models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between dietary fibre intake and the risk of IBD, CD and UC. RESULTS: During an average follow-up of 12.1 years, we ascertained 1473 incident IBD cases, including 543 cases of CD and 939 cases of UC. Comparing the lowest quintiles, an inverse association was observed between dietary fibre intake and risk of IBD (HR 0.74, 95% CI 0.58-0.93, p = 0.011) and CD (HR 0.48, 95% CI 0.32-0.72, p < 0.001), but not UC (HR 0.92, 95% CI 0.69-1.24, p = 0.595). For specified sources, dietary fibre intake from fruit and bread decreased the risk of CD, while dietary fibre intake from cereal decreased the risk of UC. CONCLUSIONS: Higher consumption of dietary fibre was associated with a lower risk of IBD and CD, but not UC. Our findings support current recommendations to increase the intake of dietary fibre.

Anti-TNF Agents and New Biological Agents (Vedolizumab and Ustekinumab) in the Prevention and Treatment of Postoperative Recurrence After Surgery in Crohn's Disease.

Surgery for Crohn's disease (CD) is not curative, as postoperative recurrence (POR) after ileocolonic resection is the rule in the absence of prophylactic treatment. In the present article, we critically review available data on the role of anti-tumour necrosis factor (TNF) agents and new biologics (including vedolizumab and ustekinumab) in the prevention and treatment of POR after surgery in CD. Several studies (summarised in various meta-analyses) have confirmed the efficacy of anti-TNFs in the prevention of POR. We identified 37 studies, including 1863 CD patients, with mean endoscopic POR at 6-12 months of 29%. Only few randomised controlled trials (RCTs) have directly compared thiopurines and anti-TNFs, with controversial results, although the superiority of the latter is supported by several meta-analyses. Infliximab and adalimumab seem equally effective. The combination of anti-TNFs and immunosuppressives should be considered in patients previously exposed to anti-TNFs. Several studies have shown that anti-TNFs remain an effective option to prevent POR also in patients with anti-TNF failure before surgery. In fact, the use of the same anti-TNF before and after surgery might be effective for the prevention of POR. Prophylactic anti-TNF treatment, once started, should be continued long term. Anti-TNFs are also effective for the treatment of established POR. Retreatment with anti-TNFs for POR is a valid strategy even after their preoperative failure. In six studies (including 156 patients) evaluating vedolizumab, mean endoscopic POR at 6-12 months was 41%. The non-randomised comparison of anti-TNFs and vedolizumab has provided controversial results. One placebo-controlled RCT confirmed that vedolizumab is quite effective in preventing POR in CD patients with increased risk of recurrence. Seven studies (including 162 patients) evaluated ustekinumab, with a mean endoscopic POR at 6-12 months of 41%. The comparative efficacy of ustekinumab and anti-TNFs is still unclear. Ustekinumab and vedolizumab seem to be equally effective, although the experience is very limited. In conclusion, to date, anti-TNFs are the most effective agents in preventing and treating POR in CD. Anti-TNFs remain an effective option to prevent POR also in patients with anti-TNF failure before surgery. Vedolizumab seems to be quite effective in the prevention of POR in patients with increased risk of recurrence. Ustekinumab is probably also effective in the postoperative setting, although the comparative efficacy with anti-TNFs or vedolizumab is still unclear.

Results of the Eighth Scientific Workshop of ECCO: Prevention and Treatment of Postoperative Recurrence in Patients With Crohn's Disease Undergoing an Ileocolonic Resection With Ileocolonic Anastomosis.

Despite the introduction of biological therapies, an ileocolonic resection is often required in patients with Crohn's disease [CD]. Unfortunately, surgery is not curative, as many patients will develop postoperative recurrence [POR], eventually leading to further bowel damage and a decreased quality of life. The 8th Scientific Workshop of ECCO reviewed the available scientific data on both prevention and treatment of POR in patients with CD undergoing an ileocolonic resection, dealing with conventional and biological therapies, as well as non-medical interventions, including endoscopic and surgical approaches in case of POR. Based on the available data, an algorithm for the postoperative management in daily clinical practice was developed.

Diet Quality and Risk of Older-onset Crohn's Disease and Ulcerative Colitis.

BACKGROUND: We aimed to assess the relationship between diet quality and risk of older-onset Crohn's disease [CD] and ulcerative colitis [UC]. METHODS: We conducted a prospective cohort study of 83 147 participants from the Swedish Mammography Cohort and the Cohort of Swedish Men. We used food frequency questionnaires to calculate adherence scores to multiple derived healthy diet patterns: Alternate Healthy Eating Index [AHEI], Healthy Eating Index-2015 [HEI-2015], Healthful Plant-Based Diet Index [HPDI], and modified Mediterranean Diet Score [mMED] at baseline in 1997 in both cohorts. Diagnoses of CD and UC were retrieved from the Swedish Patient Register. We used Cox proportional hazards modelling to estimate the adjusted hazard ratios [HRs] and 95% confidence intervals [CIs]. RESULTS: Through December of 2017, we confirmed 164 incident cases of CD and 395 incident cases of UC. Comparing the highest with the lowest quartiles, the adjusted HRs of CD were 0.73 [95% CI, 0.48, 1.12, ptrend = 0.123] for AHEI; 0.90 [0.57, 1.41, ptrend = 0.736] for HEI 2015; 0.52 [95% CI 0.32, 0.85, ptrend = 0.011] for HPDI; and 0.58 [95% CI 0.32, 1.06, ptrend = 0.044] for mMED. In contrast, we did not observe an association between any diet quality score and risk of UC. CONCLUSIONS: We found that several healthy eating patterns were associated with a lower risk of older-onset CD. Our findings provide a rationale for adapting different healthy dietary patterns based on individuals' food preferences and traditions in designing future prevention strategies for IBD.

Ustekinumab and vedolizumab for the prevention of postoperative recurrence of Crohn's disease: Results from the ENEIDA registry.

BACKGROUND: Anti-TNF agents are the only effective biological agents for the prevention of postoperative recurrence (POR) in Crohn's disease (CD). However, they are contraindicated or have been shown to fail in some patients. Although ustekinumab and vedolizumab were licensed for CD some years ago, data in this setting are scarce. METHODS: All CD patients in whom ustekinumab or vedolizumab was prescribed for the prevention of POR within three months of ileocolonic resection with anastomosis were identified from the ENEIDA registry. The development of endoscopic, clinical and surgical POR was registered. RESULTS: Forty patients were treated for the prevention of POR with ustekinumab and 25 were treated with vedolizumab. Eighty per cent had at least one risk factor for POR (prior resections, active smoking, perianal disease or penetrating disease behaviour). All the patients had been exposed to anti-TNF therapy. After a median follow-up of 17 and 26 months, the cumulative probability of clinical POR at 12 months after surgery was 32% and 30% for ustekinumab and vedolizumab, respectively. Endoscopic assessment within the first 18 months after surgery was available for 80% of the patients on ustekinumab and 70% for those on vedolizumab. The rate of endoscopic POR was 42% for ustekinumab and 40% for vedolizumab. One patient treated with ustekinumab and two with vedolizumab underwent a new intestinal resection. CONCLUSIONS: Ustekinumab and vedolizumab seem to be effective in the prevention of POR in patients at high risk. Our results warrant controlled trials comparing these drugs with conventional therapies.

Top-down Versus Step-up Strategies to Prevent Postoperative Recurrence in Crohn's Disease.

BACKGROUND: The best management after ileocolonic resection is still unknown in Crohn's disease (CD). We compared step-up and top-down approaches to prevent short and long-term postoperative recurrences in CD patients. METHODS: From a comprehensive database, consecutive CD patients who underwent intestinal resection (2014-2021) were included. Top-down (biologics started within the first month after surgery) or step-up strategies (no biologic between surgery and colonoscopy at 6 months) were performed with systematic colonoscopy at 6 months and therapeutic escalation if Rutgeerts index was ≥i2a (endoscopic postoperative recurrence). Propensity score analysis was applied for each comparison. RESULTS: Among 115 CD patients, top-down was the most effective strategy to prevent endoscopic postoperative recurrence (46.8% vs 65.9%, P = .042) and to achieve complete endoscopic remission (Rutgeerts index = i0; 45.3% vs 19.3%; P = .004) at 6 months. We did not observe any significant difference between the 2 groups regarding clinical postoperative recurrence (hazard ratio [HR], .86 [0.44-1.66], P = .66) and progression of bowel damage (HR, 0.81 [0.63-1.06], P = .12). Endoscopic postoperative recurrence at 6 months was associated with increased risk of clinical postoperative recurrence (HR, 1.97 [1.07-3.64], P 0.029) and progression of bowel damage (HR, 3.33 [1.23-9.02], P = .018). Among the subgroup without endoscopic postoperative recurrence at 6 months, the risks of clinical postoperative recurrence and progression of bowel damage were significantly improved in the top-down group (HR, 0.59 [0.37-0.94], P = .025; and HR, 0.73 [0.63-0.83], P < .001, respectively). CONCLUSIONS: Top-down strategy should be the preferred management to prevent short and long-term postoperative recurrence in CD.

Our data suggest that top-down strategy should be preferred to step-up approach to prevent endoscopic postoperative recurrence, as well as clinical postoperative recurrence and progression of bowel damage in most of the patients with Crohn's disease after bowel resection.

Benefit of Risk-stratified Prophylactic Treatment on Clinical Outcome in Postoperative Crohn's Disease.

BACKGROUND AND AIMS: Whereas immediate postoperative treatment has shown effectiveness in reducing endoscopic postoperative recurrence [POR], evidence regarding the clinical benefit is limited. We compared rates of clinical POR in Crohn's disease [CD] patients receiving immediate prophylactic treatment with rates in patients receiving endoscopy-driven treatment. METHODS: We retrospectively collected data from 376 consecutive CD patients who underwent an ileocaecal resection with anastomosis between 2007 and 2018 with at least 3 years of follow-up at three sites. Subsequently, high- and low-risk patients categorised by established guidelines, who underwent endoscopy within 12 months postoperatively, were grouped according to a prophylactic- or endoscopy-driven approach and compared for incidence and time till endoscopic and clinical POR. RESULTS: Prophylactic treatment reduced rates of and time till endoscopic POR within 1 year in high-risk (hazard ratio [HR] 0.48, 95% confidence interval [CI] 0.27-0.86, p = 0.04, number needed to treat [NNT] = 5) but not low-risk [HR 0.90, 95% CI 0.32-2.56, p = 0.85] patients. Conversely, no significant differences in clinical POR within 3 years between prophylactic- and endoscopy-driven low-risk [HR 1.17, 95% CI 0.41-3.29, p = 0.75] and high-risk patients were observed [HR 1.06, 95% CI 0.63-1.79, p = 0.82, NNT = 22]. However, a large numerical albeit not statistical significant difference in 3-year clinical POR [28.6% vs. 62.5%, p = 0.11] in a subset of high-risk patients with three or more ECCO-defined risk factors was observed, indicating a cumulative effect of having multiple risk factors. CONCLUSION: Our observations favour step-up treatment guided by early endoscopic evaluation with prophylactic treatment reserved for carefully selected high-risk patients, in order to avoid potential overtreatment of a significant number of patients.

Prevention of post-operative recurrence of Crohn's disease among patients with prior anti-TNFα failure: A retrospective multicenter study.

BACKGROUND: Anti-TNFα are recommended for preventing Crohn's disease (CD) postoperative recurrence (POR) in patients with risk factors. However, few data exploring anti-TNFα efficacy in patients with preoperative anti-TNFα failure are available so far. AIMS: The aim of the present study was to compare the efficacy of anti-TNFα with other biologics and immunosuppressants to prevent POR in this setting. METHODS: Consecutive CD patients who underwent bowel resection between January 2010 and December 2019 after failure of at least one anti-TNFα were retrospectively included among three tertiary centers if they started a postoperative medical prophylaxis within the three months after index surgery. The main outcome was to compare rates of objective recurrence (endoscopic or radiological recurrence in absence of colonoscopy) between patients treated with an anti-TNFα agent or another treatment as prevention of POR. RESULTS: Among the 119 patients included, 71 patients received an anti-TNFα (26 infliximab, 45 adalimumab) and 48 another treatment (18 ustekinumab, 7 vedolizumab, 20 azathioprine and 3 methotrexate) to prevent POR. Rates of objective recurrence at two years were 23.9% in patients treated with anti-TNFα and 44.9% in the others (p = 0.011). CONCLUSION: Anti-TNFα remained an effective option to prevent POR for patients operated upon with previous anti-TNFα failure.

Selected Aspects of Nutrition in the Prevention and Treatment of Inflammatory Bowel Disease.

Inflammatory bowel disease has become a global health problem at the turn of the 21st century. The pathogenesis of this disorder has not been fully explained. In addition to non-modifiable genetic factors, a number of modifiable factors such as diet or gut microbiota have been identified. In this paper, the authors focus on the role of nutrition in the prevention of inflammatory bowel disease as well as on the available options to induce disease remission by means of dietary interventions such as exclusive and partial enteral nutrition in Crohn's disease, the efficacy of which is reported to be comparable to that of steroid therapy. Diet is also important in patients with inflammatory bowel disease in the remission stage, during which some patients report irritable bowel disease-like symptoms. In these patients, the effectiveness of diets restricting the intake of oligo-, di-, monosaccharides, and polyols is reported.

Endoscopic Postoperative Recurrence in Crohn's Disease After Curative Ileocecal Resection with Early Prophylaxis by Anti-TNF, Vedolizumab or Ustekinumab: A Real-World Multicentre European Study.

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.

Prophylactic Antitubercular Therapy Is Associated With Accelerated Disease Progression in Patients With Crohn's Disease Receiving Anti-TNF Therapy: A Retrospective Multicenter Study.

INTRODUCTION: Prophylactic antitubercular therapy (ATT) is widely prescribed in patients with Crohn's disease (CD) receiving antitumor necrosis factor (anti-TNF) treatment. However, antitubercular agents have been demonstrated to possess profibrotic effects. We aimed to evaluate whether ATT accelerated disease progression in patients with CD receiving anti-TNF treatment. METHODS: A retrospective, multicenter study was performed in CD patients presented with inflammatory behavior (B1) and treated with anti-TNF agents. Disease progression was defined as the development of a stricturing (B2) or penetrating (B3) phenotype. ATT users were propensity score-matched with non-ATT users. Survival and multivariable Cox analyses were used to identify factors associated with disease progression. RESULTS: We enrolled 441 patients, including 295 ATT users and 146 non-ATT users, with a median follow-up of 3.15 years (interquartile range: 1.6-4.7). The cumulative rates of disease progression in the ATT group were constantly higher than those in the non-ATT group after 1-, 3-, 5-, and 10-year follow-ups, respectively (P = 0.031). Multivariable Cox analysis identified ATT as an independent risk factor for disease progression using both the whole (hazard ratio = 2.22; 95% confidence interval: 1.11-4.48; P = 0.025) and propensity score-matched cohorts (hazard ratio = 2.35; 95% confidence interval: 1.07-5.14; P = 0.033). In subgroup analysis, patients receiving ATT ≥4.5 months had a significantly higher rate of disease progression compared with patients receiving ATT <4.5 months (P = 0.005) and non-ATT treatment (P = 0.036). DISCUSSION: Prophylactic ATT with duration over 4.5 months was associated with disease progression in patients with CD receiving anti-TNF treatment.