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Background: The prevalence of obesity and the number of bariatric surgeries in both the general population and in patients with inflammatory bowel disease (IBD) have increased significantly in recent years. Due to small sample sizes and the lack of adequate controls, no definite conclusions can be drawn from the available studies on the safety and efficacy of bariatric surgery (BS) in patients with IBD. Our aim was to assess safety, weight loss, and deficiencies in patients with IBD and obesity who underwent BS and compare findings to a control group., Methods: Patients with IBD and a history of BS were retrospectively recruited to centers belonging to the Groupe d'Etude Thérapeutique des Affections Inflammatoires du Tube Digestif (GETAID). Patients were matched 1:2 for age, sex, body mass index (BMI), hospital of surgery, and type of BS with non-IBD patients who underwent BS. Complications, rehospitalizations, weight, and deficiencies after BS were collected in cases and controls., Results: We included 88 procedures in 85 patients (64 Crohn's disease, 20 ulcerative colitis, 1 unclassified IBD) with a mean BMI of 41.6 ± 5.9 kg/m2. Bariatric surgery included Roux-en-Y gastric bypass (n = 3), sleeve gastrectomy (n = 73), and gastric banding (n = 12). Eight (9%) complications were reported, including 4 (5%) requiring surgery. At a mean follow-up of 34 months, mean weight was 88.6 ± 22.4 kg. No difference was observed between cases and controls for postoperative complications (P = .31), proportion of weight loss (P = .27), or postoperative deficiencies (P = .99)., Conclusions: Bariatric surgery is a safe and effective procedure in patients with IBD and obesity; outcomes in this patient group were similar to those observed in a control population., (© 2021 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Vedolizumab clinical decision support tool (VDZ-CDST) predicts response to vedolizumab, but whether this tool also predicts efficacy of other drugs in Crohn's disease (CD) is unknown. This study aimed to assess the value of VDZ-CDST to predict vedolizumab and ustekinumab efficacy in patients with CD., Patients and Methods: We included consecutive CD patients refractory or intolerant to anti-TNF who started either vedolizumab or ustekinumab in 5 university hospitals between May 2014 and August 2018. The main end points were the rates of clinical remission and steroid-free clinical remission (SFCR) in each group of VDZ-CDST at week 48., Results: One hundred eighty patients were included; 94 received vedolizumab (VDZ-CDST ≤13: 32; VDZ-CDST >13 and ≤19: 52; VDZ-CDST >19: 10), and 86 received ustekinumab (VDZ-CDST ≤13: 16; VDZ-CDST >13 and ≤19: 60; VDZ-CDST >19: 10). At week 48 in the vedolizumab group, clinical remission and SFCR were reached in 9.4% with a VDZ-CDST ≤13, in 38.5% and 28.8% with a VDZ-CDST >13 and ≤19, respectively, and in 80.0% with a VDZ-CDST >19 (P < 0.0001 and P < 0.0001, respectively). In the ustekinumab cohort, clinical remission and SFCR were reached in 43.8% and 37.5% with a VDZ-CDST ≤13, in 55.0% and 50.0% with a VDZ-CDST >13 and ≤19, and 50.0% with a VDZ-CDST >19, respectively (P = 0.65 and P = 0.46, respectively). VDZ-CDST identified SFCR with an area under the curve of 0.69 (95% CI, 0.57-0.82) for vedolizumab and 0.52 (95% CI, 0.40-0.65) for ustekinumab., Conclusion: The VDZ-CDST predicts clinical remission and SFCR at week 48 for vedolizumab but not for ustekinumab in CD patients refractory or intolerant to anti-TNF., (© 2021 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Aims: Persons with inflammatory bowel disease (IBD) may be particularly vulnerable to COVID-19 either because of their underlying disease or its management. Guidance has been presented on the management of persons with IBD in the time of this pandemic by different groups. We aimed to determine how gastroenterologists around the world were approaching the management of IBD., Methods: Members of the World Gastroenterology Organization (WGO) IBD Task Force contacted colleagues in countries largely beyond North America and Europe, inviting them to review the WGO website for IBD and COVID-19 introduction, with links to guideline documents, and then to respond to 9 ancillary open-ended management questions., Results: Fifty-two gastroenterologists from 33 countries across 6 continents completed the survey (April 14 to May 16, 2020). They were all adhering for the most part to published guidelines on IBD management in the COVID-19 era. Some differences and reductions in services related to access, and some related to approach within their communities in terms of limiting virus spread. In particular, most gastroenterologists reduced in-person clinics (43 of 52), limited steroid use (47 of 51), limited elective endoscopy (45 of 52), and limited elective surgeries (48 of 51). If a patient was diagnosed with COVID-19, immunomodulatory therapy was mostly held., Conclusions: In most countries, the COVID-19 pandemic significantly altered the approach to persons with IBD. The few exceptions were mostly based on low burden of COVID-19 in individual communities. Regardless of resources or health care systems, gastroenterologists around the world took a similar approach to the management of IBD., (© 2020 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: A low vitamin D status has been put forward as a potential risk factor for the development of inflammatory bowel disease (IBD). This study investigated the association between prediagnostic circulating vitamin D concentrations and dietary intakes of vitamin D, and the risk of Crohn's disease (CD) and ulcerative colitis (UC)., Methods: Among 359,728 participants of the European Prospective Investigation into Cancer and Nutrition cohort, individuals who developed CD or UC after enrollment were identified. Each case was matched with2 controls by center, gender, age, date of recruitment, and follow-up time. At cohort entry, blood samples were collected and dietary vitamin D intakes were obtained from validated food frequency questionnaires. Serum 25-hydroxyvitamin D levels were measured using liquid chromatography-tandem mass spectrometry. Conditional logistic regression was performed to determine the odds of CD and UC., Results: Seventy-two participants developed CD and 169 participants developed UC after a median follow-up of 4.7 and 4.1 years, respectively. Compared with the lowest quartile, no associations with the 3 higher quartiles of vitamin D concentrations were observed for CD (p trend = 0.34) or UC (p trend = 0.66). Similarly, no associations were detected when serum vitamin D levels were analyzed as a continuous variable. Dietary vitamin D intakes were not associated with CD (p trend = 0.39) or UC (p trend = 0.83)., Conclusions: Vitamin D status was not associated with the development of CD or UC. This does not suggest a major role for vitamin D deficiency in the etiology of IBD, although larger studies are needed to confirm these findings.

Background: Oxidative stress may be involved in the aetiology of inflammatory bowel disease and whether dietary polyphenols, which possess antioxidants properties, prevent its development is unknown., Methods: A total of 401,326 men and women aged 20 to 80 years from 8 countries were recruited between 1991 and 1998 and at baseline completed validated food frequency questionnaires. Dietary polyphenol intake was measured using Phenol-Explorer, a database with information on the content of 502 polyphenols. Incident cases of Crohn's diseases (CD) and ulcerative colitis (UC) were identified during the follow-up period of up to December 2010. A nested case-control study using conditional logistic regression estimated the odds ratios (ORs), and 95% confidence intervals, for polyphenol intake (categories based on quartiles) and developing CD or UC., Results: In total, 110 CD (73% women) and 244 UC (57% women) cases were identified and matched to 440 and 976 controls, respectively. Total polyphenol intake was not associated with CD (P trend = 0.17) or UC (P trend = 0.16). For flavones and CD, there were reduced odds for all quartiles, which were statistically significant for the third (OR3rd versus 1st quartile = 0.33; 95% confidence interval, 0.15-0.69) and there was an inverse trend across quartiles (P = 0.03). Similarly, for resveratrol, there was an inverse association with CD (OR4th versus 1st quartile = 0.40; 95% confidence interval, 0.20-0.82) with an inverse trend across quartiles (P = 0.02). No significant associations between subtypes of polyphenols and UC were found. Effect modification by smoking in CD was documented with borderline statistical significance., Conclusions: The data supports a potential role of flavones and resveratrol in the risk of developing CD; future aetiological studies should investigate these dietary components and further examine the potential for residual confounding.

Background: Cytomegalovirus (CMV) is frequently detected in patients with ulcerative colitis (UC). The impact of CMV infection on the outcome of UC exacerbation remains unclear. The benefit of combining antiviral with anti-inflammatory treatment has not been evaluated yet. The aim of this study was to compare the outcome of CMV-positive hospitalized patients with UC treated with antiviral therapy either alone or combined with salvage anti-inflammatory therapy (infliximab [IFX] or cyclosporine A [CsA])., Methods: This was a multicenter retrospective study of hospitalized CMV-positive patients with UC. The patients were classified into 2 groups: antiviral-if treated with antivirals alone; combined-if treated with both antiviral and anti-inflammatory therapy. The outcomes included the rate of colectomy in both arms during the course of hospitalization and after 3/12 months., Results: A total of 110 patients were included; 47 (42.7%) patients did not receive IFX nor CsA; 36 (32.7%) received IFX during hospitalization or within 1 month before hospitalization; 20 (18.1%) patients received CsA during hospitalization; 7 (6.4%) were exposed to both IFX and CsA. The rate of colectomy was 14.5% at 30 days, 20.0% at 3 months, and 34.8% at 12 months. Colectomy rates were similar across treatment groups. No clinical and demographic variables were independently associated with the risk of colectomy., Conclusions: IFX or cyclosporine therapy is not associated with additional risk for colectomy over antiviral therapy alone in hospitalized CMV-positive patients with UC.

Background: Dairy products may be involved in the etiology of inflammatory bowel disease by modulating gut microbiota and immune responses, but data from epidemiological studies examining this relationship are limited. We investigated the association between prediagnostic intake of these foods and dietary calcium, and the subsequent development of Crohn's disease (CD) and ulcerative colitis (UC)., Methods: In total, 401,326 participants were enrolled in the European Prospective Investigation into Cancer and Nutrition cohort. At recruitment, consumption of total and specific dairy products (milk, yogurt, and cheese) and dietary calcium was measured using validated food frequency questionnaires. Cases developing incident CD (n = 110) or UC (n = 244) during follow-up were matched with 4 controls. Conditional logistic regression analyses were used to calculate odds ratios (ORs) with 95% confidence intervals (CIs), adjusted for total energy intake and smoking., Results: Compared with the lowest quartile, the ORs for the highest quartile of total dairy products and dietary calcium intake were 0.61 (95% CI, 0.32-1.19, p trend = 0.19) and 0.63 (95% CI, 0.28-1.42, p trend = 0.23) for CD, and 0.80 (95% CI, 0.50-1.30, p trend = 0.40) and 0.81 (95% CI, 0.49-1.34, p trend = 0.60) for UC, respectively. Compared with nonconsumers, individuals consuming milk had significantly reduced odds of CD (OR 0.30, 95% CI, 0.13-0.65) and nonsignificantly reduced odds of UC (OR 0.85, 95% CI, 0.49-1.47)., Conclusions: Milk consumption may be associated with a decreased risk of developing CD, although a clear dose-response relationship was not established. Further studies are warranted to confirm this possible protective effect.

Background: Specific nutrients or foods have been inconsistently associated with ulcerative colitis (UC) or Crohn's disease (CD) risks. Thus, we investigated associations between diet as a whole, as dietary patterns, and UC and CD risks., Methods: Within the prospective EPIC (European Prospective Investigation into Cancer) study, we set up a nested matched case-control study among 366,351 participants with inflammatory bowel disease data, including 256 incident cases of UC and 117 of CD, and 4 matched controls per case. Dietary intake was recorded at baseline from validated food frequency questionnaires. Incidence rate ratios of developing UC and CD were calculated for quintiles of the Mediterranean diet score and a posteriori dietary patterns produced by factor analysis., Results: No dietary pattern was associated with either UC or CD risks. However, when excluding cases occurring within the first 2 years after dietary assessment, there was a positive association between a "high sugar and soft drinks" pattern and UC risk (incidence rate ratios for the fifth versus first quintile, 1.68 [1.00-2.82]; Ptrend = 0.02). When considering the foods most associated with the pattern, high consumers of sugar and soft drinks were at higher UC risk only if they had low vegetables intakes., Conclusions: A diet imbalance with high consumption of sugar and soft drinks and low consumption of vegetables was associated with UC risk. Further studies are needed to investigate whether microbiota alterations or other mechanisms mediate this association.

Background: Diet may have a role in the etiology of inflammatory bowel disease. In previous studies, the associations between increased intakes of carbohydrates, sugar, starch, and inflammatory bowel disease are inconsistent. However, few prospective studies have investigated the associations between these macronutrients and incident Crohn's disease (CD) or ulcerative colitis (UC)., Methods: A total of 401,326 men and women were recruited between 1991 and 1998. At recruitment, dietary intakes of carbohydrate, sugar, and starch were measured using validated food frequency questionnaires. The cohort was monitored identifying participants who developed incident CD or UC. Cases were matched with 4 controls, and odds ratios were calculated for quintiles of total carbohydrate, sugar, and starch intakes adjusted for total energy intake, body mass index, and smoking., Results: One hundred ten participants developed CD, and 244 participants developed UC during follow-up. The adjusted odds ratio for the highest versus the lowest quintiles of total carbohydrate intake for CD was 0.87, 95% CI = 0.24 to 3.12 and for UC 1.46, 95% CI = 0.62 to 3.46, with no significant trends across quintiles for either (CD, P trend = 0.70; UC, P trend = 0.41). Similarly, no associations were observed with intakes of total sugar (CD, P trend = 0.50; UC, P trend = 0.71) or starch (CD, P trend = 0.69; UC, P trend = 0.17)., Conclusions: The lack of associations with these nutrients is in agreement with many case-control studies that have not identified associations with CD or UC. As there is biological plausibility for how specific carbohydrates could have an etiological role in inflammatory bowel disease, future epidemiological work should assess individual carbohydrates, although there does not seem to be a macronutrient effect.

Background: Crohn's disease (CD) is associated with an increased risk of small bowel adenocarcinoma (SBA). However, there are no guidelines for the screening and early diagnosis of SBA. Colorectal cancer associated with chronic colitis arises from dysplasia. High-risk patients benefit from surveillance colonoscopies aimed to detect dysplasia. The dysplasia-carcinoma sequence remains poorly documented in CD-associated SBA. Moreover, molecular data about SBA complicating CD and associated dysplasia are very limited. We therefore assessed dysplasia and several key molecular markers of carcinogenesis in SBA and dysplasia developed in patients with CD., Methods: Forty-five SBA complicating CD and 4 specimens with dysplasia without SBA were screened. In SBA, we looked for dysplasia and determined their pathological characteristics (type, grade, distribution). We also stained for mismatch repair proteins (MLH1, MSH2, MSH6, PMS2), p53, β-catenin, and p16 and looked for KRAS, BRAF and PIK3CA mutations., Results: All neoplastic lesions, except 1 lesion, were found in inflamed mucosal areas. Dysplasia was found in 20 of 41 patients with SBA (49%). Dysplasia was flat or raised, low grade or high grade, and adjacent or distant to concomitant SBA. Molecular markers of SBA carcinogenesis complicating CD were similar to those observed in chronic colitis-related colorectal cancer (KRAS, BRAF, p53, MSI), although differences were observed for β-catenin and p16. No PIK3CA mutations were observed., Conclusions: These results suggest that there is an inflammation-dysplasia-adenocarcinoma sequence in at least half of CD-related SBA, similar to what is observed in chronic colitis-related colorectal cancer and may have implications for the prevention and treatment of this cancer.

Background: Vitamin D insufficiency has been suggested to be associated with high risk of Crohn's disease (CD). In France, where food fortification is limited, the major source of vitamin D is through sun exposure. The aim of this work was to analyze the relationship between residential sun exposure and the risk of incident CD or ulcerative colitis (UC)., Methods: The E3N cohort consists of women living in France, aged 40 to 65 years and free of major diseases at inclusion in 1990. Among the 91,870 women included in the study, we identified 123 incident cases (45 CD, 71 UC, and 7 indeterminate colitis). To assess residential sun exposure, we used a database containing mean daily ultraviolet radiation (UVR) dose for each French county. The relationship between residential sun exposure and risk of incident inflammatory bowel diseases was explored using Cox models., Results: Higher levels of residential sun exposure were associated with a significant decreased risk of CD (hazard ratio [HR] for the third versus the first tertile of UVR dose, 0.49; 95% confidence interval (CI), 0.23-1.01; P for trend = 0.04), but not of UC (HR, 1.21; CI, 0.61-2.11). In women with available data on dietary vitamin D intake, we observed a lower risk of CD with higher residential UVR (HR, 0.29; 95% CI, 0.11-0.80; P for trend = 0.01). Dietary vitamin D intake was neither associated with the risk of CD (HR, 0.41; 95% CI, 0.14-1.24; P for trend = 0.14) nor UC (HR, 1.61; CI, 0.61-4.23)., Conclusions: In this prospective cohort of women, high residential sunlight exposure was associated with decreased incidence of CD, but not UC.

Background: Patients with Crohn's disease (CD) of the colon are at risk for colorectal cancer and should be screened for dysplasia and cancer of the colon. Small bowel adenocarcinoma (SBA) is a complication of small bowel CD and carries a poor prognosis. However, there is no screening test for SBA in patients with small bowel CD. The aim of this study was to assess the risk and incidence of SBA in a large prospective cohort of patients with small bowel CD and to compare it with the risk of colorectal cancer in patients with CD involving the colon, recruited in the same cohort., Methods: In a nationwide French cohort, 11,759 patients with CD were enrolled by 680 gastroenterologists. The SBA risk was obtained by dividing the observed cases in our cohort to the expected cases in the general population., Results: At baseline, 8222 (69.9%) patients had small bowel CD (either alone or associated with colonic CD); their median follow-up was 35 months (interquartile range, 29-40). Five new cases of SBA were diagnosed, all in patients with small bowel CD, within inflamed areas. Among the 5 patients with incident SBA, 4 died of SBA and 1 is in remission 7 years after the diagnosis of SBA. The incidence rates of SBA were 0.235 per 1000 patient-years (95% confidence interval [CI], 0.076-0.547) among patients with small bowel CD and 0.464 per 1000 patient-years (95% CI, 0.127-1.190) among those with small bowel CD for >8 years. This accounted for approximately 30% of the risk of colorectal cancer in patients with CD of the colon. Patients with small bowel CD and small bowel CD for >8 years had an SBA standardized incidence ratio of 34.9 (95% CI, 11.3-81.5) and 46.0 (95% CI, 12.5-117.8), respectively., Conclusions: SBA in patients with small bowel CD carries a poor prognosis, and its risk is approximately 30% of colorectal cancer risk in patients with CD of the colon. Further studies should determine if small bowel endoscopic screening in high-risk patients is feasible and effective.

Background: In a previous study we found a north-south gradient for Crohn's disease (CD) incidence in France. The aim of the present study was to determine if socioeconomic factors may influence the geographic distribution of CD and ulcerative colitis (UC) in France., Methods: Using the national health insurance databases, incidence rates of CD and UC were estimated for each of 341 metropolitan "job areas" in 2000-2002. Relationships between incidence rates and relevant contextual variables from the 1999 French census were tested for significance using a Poisson regression. Mapping of smoothed relative risks (sRR) for CD and UC at the scale of job areas, using a Bayesian approach and adjusting for significant contextual variables, was carried out in order to search for geographic variations., Results: CD incidence rates were negatively related to the percentage of farmers and to the percentage of housing with bathroom and toilets and positively related to the unemployment rate and to the percentage of households below the poverty threshold. Mapping of sRR for CD showed a clear north-south gradient, which was slightly improved after including the percentage of farmers and the percentage of housing with toilets. In UC we found no significant correlation between either incidence and socioeconomic variables or incidence and house equipment variables, and there was no north-south gradient. However, there was a positive and significant correlation between CD and UC incidence., Conclusions: The present study shows that geographic risk factors of CD in France are northern latitude, nonrural areas, and areas with poor sanitary house equipment. Among these factors the most important is northern latitude.

Background: Intravenous cyclosporine is active in 60% to 80% of patients with ulcerative colitis (UC) who failed to respond to intravenous corticosteroids. Several studies have suggested that cyclosporine in microemulsion form (Neoral) has some efficacy in this setting, but the optimal dose, blood level, time to response, and remission need to be better defined. The aim of this study was to evaluate the response to Neoral and its toxicity in active corticosteroid-refractory UC., Methods: Between March 2002 and August 2005, 20 courses of Neoral [initial dose, 2.3 mg/kg (range, 1.8 to 2.8 mg/kg) every 12 hours] were prescribed in 19 consecutive patients for a UC attack that did not respond to intravenous methylprednisolone. All patients received prophylaxis against Pneumocystis carinii., Results: Response was obtained in 17 of 20 attacks (85%) after 3.5 days (range, 1 to 7). Remission was obtained in 15 of 20 attacks (75%) after 13 days (range, 2 to 30 days). Four responders relapsed and underwent colectomy 21 to 900 days after the start of Neoral. Overall, 14 of 19 patients (74%) were colectomy free after a median follow-up of 8 months (range, 1 to 41 months). Cyclosporine blood levels were measured at fasting (C0) and 2 hours after Neoral administration (C2) in a subgroup of 10 responders. The results were 103 ng/mL (range, 32 to 240 ng/mL) for C0 and 761 ng/mL (183 to 1390 ng/mL) for C2. One severe bedridden patient with neonatal encephalopathy died. Main side effects observed were mild transient renal impairment (n = 2), hypertension (n = 1), cytomegalovirus infection (n = 2), and esophageal candidiasis (n = 1)., Conclusions: In active corticosteroid-refractory UC, Neoral seems to have the same efficacy and toxicity as the intravenous form. Trough target cyclosporine blood levels should not exceed 100 ng/mL for C0 and 700 ng/mL for C2.

Background and Aim: A north-south gradient in inflammatory bowel disease (IBD) incidence has been found in Europe and the United States. Its existence is inferred from comparisons of registries that cover only small portions of territories. Several studies suggest that IBD incidence in the north has reached a plateau, whereas in the south it has risen sharply. This evolution tends to reduce the north-south gradient, and it is uncertain whether it still exists. In France, patients with IBD are fully reimbursed for their health expenses by the national health insurance system, which is a potential source of data concerning the incidence of IBD at the national level. The aim of this study was to assess the geographical distribution of Crohn's disease (CD) and ulcerative colitis (UC) in France and to test the north-south gradient hypothesis., Methods: This study was conducted in metropolitan France and included patients to whom IBD reimbursement was newly attributed between January 1, 2000 and December 31, 2002. Data provided relate to age, sex, postcode area of residence, and IBD type. The mapping of geographical distribution of smoothed relative risks (RR) of CD and UC was carried out using a Bayesian approach, taking into account autocorrelation and population size in each département., Results: In the overall population, incidence rates were 8.2 for CD and 7.2 for UC per 100,000 inhabitants. A clear north-south gradient was shown for CD. Départements with the highest smoothed RR were located in the northern third of France. By contrast, the geographical distribution of smoothed RR of UC was homogeneous., Conclusions: This study shows a north-south gradient in France for CD but not for UC.

Background: Data concerning small bowel adenocarcinoma (SBA) in Crohn's disease (CD) come from case reports and small retrospective series. The aim of this study was to further describe SBA in patients with CD and compare it with SBA de novo., Methods: Twenty patients with CD with SBA recruited in French university hospitals were studied and compared with 40 patients with SBA de novo recruited from a population-based registry. SBA occurred after a median time of 15 years of CD and was located within the inflamed areas of the ileum (n=19) or jejunum (n=1), whereas in patients with SBA de novo, it was distributed all along the small intestine. Median age at diagnosis of SBA was 47 years (range, 33-72 yr) in patients with CD and 68 years (range, 41-95 yr) in those with SBA de novo., Results: The cumulative risk of SBA, assessed in a subgroup of patients, was 0.2% and 2.2% after 10 and 25 years of ileal CD, respectively. SBA accounted for 25% and 45% of the risk of gastrointestinal carcinoma after 10 and 25 years of CD, respectively. Diagnosis was made preoperatively in 1/20 patients with CD and 22/40 patients with SBA de novo. Signet ring cells were found in 35% of patients with CD but not in patients with SBA de novo. Relative survival was not significantly different in these 2 categories of patients (54 versus 37% and 35 versus 30% in patients with and without CD at 2 and 5 yr, respectively)., Conclusions: SBA in CD is different from SBA de novo. It arises from longstanding ileal inflammation and is difficult to diagnose. SBA cumulative risk increases after 10 years of CD and is likely to cause premature mortality in patients with early-onset CD.

Background: The Vienna classification of Crohn's disease (CD) distinguishes three patient subgroups according to disease behavior: stricturing, penetrating, and inflammatory. Our aim was to assess the long-term evolution of the disease behavior of CD and to determine the predictive factors and prognostic implications of this evolution., Methods: Occurrence and predictive factors of a stricturing and/or a penetrating complication were searched for in 2,002 patients with CD studied retrospectively. In addition, the 1995-2000 disease course was assessed prospectively in a cohort of 646 patients with disease duration >5 years, classified according to their previous disease behavior., Results: 1,199 patients (60%) developed a stricturing (n = 254) or a penetrating (n = 945) complication. Twenty-year actuarial rates of inflammatory, stricturing, and penetrating disease were 12, 18, and 70%, respectively. The initial location of lesions was the main determinant of the time and type of the complication. In the cohort study, year-by-year activity and therapeutic requirements did not show significant sustained differences between behavioral subgroups., Conclusion: Most patients with CD will eventually one day develop a stricturing or a perforating complication. Initial location determines the type of the complication. Classification of patients into a behavioral group from previous history has no impact upon activity during the following years.