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Objectives: Adalimumab is usually self-injected at home, making prospective serial-sampling studies challenging and scarce. This has led to a gap in knowledge about evolution of anti-adalimumab antibodies (AAAs) over time and its correlation with clinical and inflammatory outcomes., Methods: A program for home visits by physicians at induction, every 3 months and at event of relapse, was established prospectively for Crohn's disease (CD) patients. At each visit, patients' clinical scores were determined and sera were obtained for C-reactive protein, drug, and AAA levels. This cohort was compared to a parallel prospective cohort of infliximab-treated CD patients. In a subgroup of 29 patients, trough and in-between-trough levels were compared, to elucidate the importance of timing of sampling during the injection cycle., Results: Ninety-eight CD patients starting adalimumab were prospectively followed (median follow-up 44 weeks) and 621 serum samples were analyzed. Thirty-three patients (32%) developed AAA; 18/33 (55%) of them as early as week 2, and 26/33 (79%) by week 14. Induction period AAAs were strongly associated with primary non-response (odds ratio (OR) = 5.4, 95% confidence interval (CI): 1.6-17.8, p = 0.005). As compared to antibodies-to-infliximab (ATI), AAA formation rate over time was significantly lower (p = 0.01) and AAA were much more specific-85% of AAA events were associated with loss-of-response compared with 58% rate for ATI (p = 0.01). In 29 patients sampled serially during an injection cycle, levels of drug and AAA seemed comparable between four time-points during a single cycle both in patients with or without AAA (n = 8, n = 21, respectively)., Conclusions: When followed prospectively and serially, AAAs are found to arise earlier than previously appreciated and their impact may be more pronounced for primary rather than secondary, non-response. Drug and AAA levels were similar both at trough and in-between injections, enabling to simplify therapeutic drug monitoring of adalimumab.

Background and Aims: Capsule endoscopy [CE] and magnetic resonance enterography [MRE] are prime modalities for evaluation of the small bowel in Crohn's disease [CD]. Detection of proximal small bowel [SB] inflammation in CD by MRE is challenging. Currently available quantitative MRE scores do not incorporate proximal SB data. The MRE global score [MEGS] was designed for quantitative evaluation of the entire digestive tract; its accuracy in the proximal SB has not previously been evaluated. This study compared the evaluation of the small bowel inflammation by MEGS and CE-derived quantitative score (the Lewis score[LS])., Methods: CD patients in stable clinical remission were prospectively recruited and underwent MRE and CE; faecal calprotectin [FC] levels were obtained. MEGS was calculated for each SB segment and the entire SB [SBMEGS]. SB inflammation on CE was quantified using LS. A cumulative Lewis score [C-LS] was calculated based on summation of three tertiles scores., Results: Fifty patients were included. There was a significant correlation of SBMEGS with LS and C-LS [r = 0.61 and 0.71, both p = 0.001]. The correlation with FC was stronger for MEGS than for LS or C-LS [r = 0.68 vs r = 0.46 vs r = 0.53, all p = 0.001]. The correlation between the proximal LS and MEGS was significant [r = 0.55, p = 0.001]; median MEGS was significantly different in patients, with LS values consistent with mucosal healing, mild and moderate-to-severe inflammation., Conclusions: MEGS provides accurate evaluation of the SB and strongly correlates with FC; the main advantage of MEGS is the accurate quantification of proximal SB inflammation unavailable for alternative MRE scores., (Copyright © 2017 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com)

Background: Crohn's disease is associated with accumulation of progressive structural bowel damage (SBD) leading to the development of stenotic and penetrating complications. The data pertaining to the course of progression of SBD is scarce. The Lemann index (LI) is a novel tool for evaluation of SBD that incorporates pan-enteric clinical, endoscopic and imaging data., Aims: To evaluate the progression of SBD in quiescent CD patients., Methods: Patients with known quiescent small bowel Crohn's disease (CD) for at least 3 months (CDAI<220) were prospectively recruited and underwent repeated magnetic resonance enterographies (MRE) and video capsule endoscopies (VCE). Patients were assessed for SBD on initial and follow-up evaluation using relevant clinicopathological data, MRE and VCE results. Significant structural bowel damage (SBD) was identified as LI>4.8, and progression of SBD as LI>0.3., Results: Sixty one patients were enrolled in the study. Significant SBD was detected 13 (21.4%) on enrollment. Duration of disease (p=0.036) and history of CD-related surgery (p=0.0001) were associated with significant BD. Forty one patients underwent a follow-up MRE (14.8±2.5 months apart). LI was similar at baseline and follow-up. There was a negligible change in LI between the evaluations., Conclusions: In patients with quiescent Crohn's disease, structural bowel damage was stable over a median of 14 months follow-up., (Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Helicobacter pylori (HP) infection is present in about 50% of the global population, and is associated with chronic gastritis, peptic disease and gastric malignancies. HP prevalence in Crohn's disease (CD) patients was shown to be low compared to the general population, and its influence on disease activity is yet to be determined. Our aims were to determine the prevalence of HP in a selected group of CD patients with quiescent disease, and to assess the influence of its eradication on disease activity and endoscopic and laboratory activity measures., Methods: Consecutive CD patients with quiescent disease underwent meticulous disease evaluation with MR enterography (MRE), video capsule endoscopy (VCE), CRP, fecal calprotectin and CDAI. All patients were tested for the presence of HP using stool antigen detection kit. Patients infected with HP were offered eradication treatment with sequential therapy. HP eradication was confirmed using urease breath test and stool antigen test. The influence of HP eradication on disease activity was assessed., Results: Out of 56 patients enrolled, six patients (10.7%) had HP infection. Of them, five patients had gastro- duodenitis per VCE. All HP positive patients were offered eradication treatment and underwent successful eradication. Notably, 23 (50%) of patients had proximal disease per VCE, most of them (78%) were HP negative. CDAI, CRP, fecal calprotectin and VCE Lewis inflammatory score did not change significantly following HP eradication, Gastric findings on VCE were not impacted by HP eradication., Conclusions: The prevalence of HP infection in patients with quiescent CD is relatively low. Eradication of the bacteria did not significantly change neither disease activity measures nor the presence of gastro- duodenitis per VCE, suggesting it might be part of proximal CD. The influence of HP on CD activity merits further investigation.

Background and Aims: The classification of Crohn's disease (CD) is usually determined at initial diagnosis and is frequently based on ileocolonoscopic and cross-sectional imaging data. Advanced endoscopic and imaging techniques such as small-bowel video capsule endoscopy (VCE) and magnetic resonance enterography (MRE) may provide additional data regarding disease extent and phenotype. Our aim was to examine whether VCE or MRE performed after the initial diagnosis may alter the original disease classification., Methods: Consecutive patients with known small-bowel CD in clinical remission or mild disease were prospectively recruited and underwent MRE and VCE (if small-bowel patency was confirmed by a patency capsule (PC). Montreal classifications before and after evaluation were compared., Results: Seventy-nine patients underwent MRE and VCE was performed in 56. Previously unrecognized disease locations were detected with VCE and MRE in 51 and 25%, respectively (p < 0.01) and by both modalities combined in 44 patients (55%). Twenty-two patients (27%) were reclassified as having an advanced phenotype (B2/B3). MRE and VCE reclassified the phenotype in 26 and 11% of cases, respectively (p < 0.05). Overall, both modalities combined altered the original Montreal classification in 49/76 patients (64%)., Conclusion: VCE and MRE may lead to reclassification of the original phenotype in a significant percentage of CD patients in remission. VCE was more sensitive for detection of previously unrecognized locations, while MRE was superior for detection of phenotype shift. The described changes in the disease classification may have an important impact on both clinical management and long-term prognosis in these patients., (Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Crohn's disease (CD) is frequently associated with weight loss and malnutrition. However, as the prevalence of obesity increases worldwide, it may become a clinical problem even in CD., Aim: To assess the prevalence of severe/morbid obesity in CD patients and to compare their disease characteristics to nonobese CD patients., Methods: A retrospective analysis of a computerized CD patient database was performed to identify severely/morbidly obese patients (BMI >35). Prevalence was compared to data of the general population. Severely/morbidly obese CD patients were then compared to randomly selected nonobese CD patients (BMI <30) in a 1:3 ratio., Results: Thirteen severely/morbidly obese patients out of 560 CD patients were found (2.3%), which is significantly lower than the prevalence in the general population (5.6%, p = 0.001). When compared to 39 nonobese CD patients, colonic disease was significantly more common among severely/morbidly obese CD patients (odds ratio: 6, 95% CI: 1.35-26.3, p = 0.02), while there was no difference in other disease parameters. Interestingly, 4 morbidly obese CD patients had undergone laparoscopic sleeve gastrectomy for treatment of morbid obesity with a favorable surgical course., Conclusion: CD in severely/morbidly obese patients is more often colonic, but otherwise no different than CD in nonobese patients. Sleeve gastrectomy is a viable therapeutic option for morbidly obese CD patients., (Copyright © 2013 S. Karger AG, Basel.)

Background: There is limited data addressing the severity of Crohn's disease (CD) in patients with a family history of inflammatory bowel disease (IBD) compared to sporadic cases., Methods: We investigated the familial occurrence of IBD and its correlation with disease behavior in CD patients attending the Israeli IBD Foundation meeting using a structured questionnaire., Results: The study group consisted of 181 CD patients with a total of 825 1(st) degree relatives. Positive family history for IBD in a 1(st) degree relative was reported in 30 patients (16%). Nine out of the 360 parents (2.5%) had IBD (4 CD, 5 UC). There were 17 siblings with IBD (15 CD, 2 UC) out of 351 (4.8%). Ten out of 114 (8.8%) offsprings had IBD (6 CD, 4 UC). When two siblings were affected, their respective age of disease onset was strikingly concordant (r = 0.76, p = 0.008). There was no difference between sporadic and familial CD patients in the age of disease onset, the location of disease, proportion of smokers or percentage of Ashkenazi origin. Furthermore, similar proportions of sporadic and familial patients underwent intestinal surgery, had penetrating or obstructive complications or were treated by immunomodulators and/or biologics. There was also no difference in the reported percentage of time with active disease or the number of flare-ups., Conclusions: The prevalence of familial disease among Jewish CD patients in Israel is at the high range of the rate found in other ethnicities. Having a positive family history of IBD has no impact on the severity of the disease.

Background: Patients with Crohn disease (CD) often undergo both multislice computed tomography (MSCT) and small bowel follow-through (SBFT) for evaluation of their disease. We compared the findings on computed tomography (CT) and SBFT in patients with CD to determine whether MSCT can be the modality of choice in the evaluation of these patients., Methods: We reviewed the CT and SBFT studies of 41 patients with CD. The findings were evaluated by three experienced abdominal imagers., Results: There was no statistical difference in the detection of mural involvement of the small bowel. The CT showed additional involvement of the colon, mesenteric involvement, and extraenteric complications., Conclusion: Multislice CT is a reliable modality in demonstrating enteric as well as extraenteric pathological findings in patients with CD. We suggest that MSCT can replace SBFT in the evaluation of patients with CD.

Aim: To evaluate the prevalence and localization of the deposition of submucosal fat, the "fat halo sign" (FHS), using computed tomography (CT) in the bowel wall of patients with Crohn's Disease, and to assess its relation to the duration of the disease., Materials and Methods: The abdominal CT examinations of 100 consecutive patients were reviewed for the presence of the FHS in the bowel wall. A measurement of less than -10HU was regarded as indicative of fat. CT findings were correlated with the duration of the disease and statistically tested by simple regression analysis. The patients were divided into two groups: group A included 26 patients with a disease duration of less than 1 year and group B included 73 with a longer disease duration. In one patient disease duration was unknown. To test the relationship between disease duration and FHS the cumulative number of FHS positive and negative patients was plotted against disease duration., Results: The FHS was present in 17 of the 100 patients in 20 bowel segments, mainly in the ileum (10) and the ascending colon (8). The FHS was present in 3.8% in group A and in 21.9% in group B (p<0.0375)., Conclusion: The FHS was present in 17% of patients with CD. Its location was mainly in the terminal ileum and ascending colon, typical sites of the disease. Its prevalence was significantly duration dependent.

Background and Goals: Video capsule endoscopy (VCE) enables visualization of the entire small bowel and can identify lesions that may go undetected by conventional endoscopy and radiography. In this study, we assessed whether patient's selection based on symptoms may increase the yield of VCE in the diagnosis of Crohn's disease (CD)., Study: Findings of 125 consecutive patients referred for VCE in whom CD may be suspected, were analyzed. Indications for VCE included iron-deficiency anemia, abdominal pain, diarrhea, or a combination of symptoms. Capsule endoscopy (CE) results were defined positive if 4 or more obvious clear ulcers, erosions, or a region with clear exudate and mucosal hyperemia and edema were identified., Results: One hundred twelve patients were included in the final analysis. Mean age of patients was 44+/-22 years and median follow-up 36+/-15 months. Findings on CE were considered compatible with a diagnosis of CD in 7 patients (6%). In general, CE yielded a diagnosis of CD in a very small portion of the patients (0% to 4%), except in patients undergoing the test for a combination of abdominal pain and diarrhea. In this group, findings suggestive of inflammatory bowel disease were encountered in one-third of the patients (P=0.002)., Conclusions: The greatest yield of CE in diagnosing CD is achieved in young patients who present with symptoms of abdominal pain plus diarrhea.

Objectives: Crohn's disease (CD) has been reported to be more frequent among non-Ashkenazi Jewish patients suffering from familial Mediterranean fever (FMF). Interestingly, functional similarities between the CD susceptibility gene (NOD2/CARD15) and the FMF gene (MEFV) have been described: both belong to the death domain containing protein family, important in the regulation of apoptosis, cytokine processing and inflammation., Aims: To investigate the prevalence of MEFV mutations in Jewish non-Ashkenazi CD patients and its putative effect on CD presentation., Methods: Germline DNA of 105 Israeli CD patients of non-Ashkenazi and mixed Ashkenazi-non-Ashkenazi ethnic background was analyzed for three most common MEFV mutations: M694V, V726A, and E148Q. Five patients (4.7%) with a clinical diagnosis of FMF were included. Data obtained from each patient included: age of onset, disease location, and behavior, the presence of extraintestinal manifestations of CD and therapeutic regimens., Results: The overall prevalence of mutation carriers among non-FMF-CD patients was 13% (13/100). A stricturing disease pattern was observed in 56% (10/18) of all carriers, FMF-CD, and non-FMF-CD patients, and in 25% (22/87) of noncarriers (OR: 3.7, 95% CI: 1.3-10.5, p= 0.015). The prevalence of fistulas was comparable in both groups. Extraintestinal manifestations were significantly more frequent among carriers than noncarriers (65%vs 32%, OR 3.9, 95% CI = 1.3-11.5, p= 0.015). No differences were observed in disease location and disease severity., Conclusions: MEFV mutations are not associated with CD susceptibility, yet the presence of these mutations appears to be associated with a stricturing disease pattern and extraintestinal disease manifestations of CD.

Background: Relapse after an initial response to infliximab therapy poses a problem for maintenance treatment., Aim: To assess the effects of increasing the infliximab dosage in Crohn's disease (CD) patients who initially responded but flared during maintenance therapy., Methods: This was an observational study. Twelve CD patients with both inflammatory and fistulizing manifestations were included. All patients initially responded to 5 mg/kg of infliximab, relapsed during maintenance therapy, and were treated with 10 mg/kg. The Harvey-Bradshaw index, the fistula activity, and steroid use were assessed before and after treatment with the increased dose of infliximab., Results: The mean Harvey-Bradshaw index score after flare-up during treatment with 5 mg/kg of infliximab was 13.5+/-3.7. Treatment with 10 mg/kg, in a mean of 3.3 infusions, decreased the activity score to a mean of 8.8+/-2.5. Two patients were weaned off prednisone, and a reduced dose was possible in the other steroid-treated patients., Conclusions: Increasing the infliximab dose may be beneficial in CD patients who initially responded to therapy, but relapsed during maintenance with the lower dosage., (Copyright (c) 2005 S. Karger AG, Basel.)

Background/aims: The majority of Crohn's disease patients undergo surgery. However, the factors that predict post-operative recurrence remain controversial. The aim of the present study was to shed light on the potential predictors of such recurrence., Methods: 86 patients who underwent operative procedures for Crohn's disease were retrospectively studied. Recurrence was defined as the need for a second operation. Life table and multivariate analysis were performed to find the predictors of recurrence., Results: In 26/86 (30%) of the patients, post-operative recurrence was diagnosed within a mean of 42 months of the follow-up. Logistic regression analysis revealed that smoking (OR 3.69, 95% CI 2.06-11.52) and perforating disease (OR 4.09, 95% CI 1.31-12.65) were associated with a risk of recurrence. However, survival analysis showed that only perforating disease was associated with an early post-operative recurrence (log-rank test, p < 0.001). Neither resected surgical specimen characteristics, nor the duration and the location of the disease were found to predict the need for a second operation., Conclusion: The risk for Crohn's disease patients who undergo surgery is related to the presence of perforating disease and smoking, which predict the need for a second operation. The former is associated with an even earlier recurrence.

Objective: The main objective is to study whether the month of birth is associated with the development of Crohn's disease (CD) in the Israeli Jewish population., Background: It was suggested that perinatal exposure to infectious agents may have a role in the pathogenesis of CD. Due to the seasonal nature of some infections, a linkage between birth dates and a risk to develop CD would support such a hypothesis. Previous studies that addressed this question were conducted in Europe and differed in their findings., Methods: Birth dates of 844 Jewish ulcerative colitis (UC) and CD patients from three medical centers representing the north, central, and the south of Israel were compared with the monthly rates of birth during the same period of time. The standard incidence ratio was used to define the risk to develop either disease according to the month of birth. The Score method was used for the evaluation of seasonality trends., Results: Birth during the winter period in Israel was associated with increased risk to develop CD, whereas birth during the spring was associated with a reduced risk. The Score method for seasonality showed a significant peak during winter time in these patients (z = 2.02, p= 0.021). No such seasonal variation was noted for UC patients., Conclusions: A seasonal pattern was observed in the risk to develop CD but not UC. The findings may support the involvement of environmental factors in the pathogenesis of CD.

Ulcerative colitis (UC) and Crohn's disease (CD) are heterogeneous disorders characterized by chronic intestinal inflammation. Genetic predisposition is a major risk factor in both diseases. The CARD15 (NOD2) gene has been implied as a candidate gene in the pathogenesis CD. Our aim was to delineate the frequency of three missense and one frameshift variant of CARD15 in Israeli Jewish CD and UC patients. DNA was extracted from blood samples from 238 unrelated inflammatory bowel disease (IBD) patients, 68 with UC and 170 with CD. The DNA was genotyped for two missense mutations, R675W and G881R, and one frameshift mutation, 980FS981X. Mutations in CARD15 were observed with significantly greater frequency in CD patients (46/170, 27%) than in UC patients (7/68, 10%) (P = 0.005). Homozygous and compound heterozygous carriers were restricted to seven (4%) patients with CD as compared to none of the UC patients (P = 0.01). Similar rates in Ashkenazi and non-Ashkenazi Jewish patients were observed. Age-of-onset of disease was lower in Ashkenazi mutation carriers as compared to non-carriers of Ashkenazi origin (18.7 +/- 8.6 years vs. 25.8 +/- 13.4 years, respectively, P = 0.03). No other phenotypic characteristics could distinguish mutation carriers from non-carriers. We conclude that germline mutations in the CARD15 gene are more frequently found in CD than UC patients and appear to predict an earlier age-of-onset in Ashkenazi Jewish patients. No association could be demonstrated between CARD15 mutations and specific disease course or behavior., (Copyright 2003 Wiley-Liss, Inc.)

Background: Crohn's disease (CD) is a chronic transmural inflammatory disease of unknown etiology. Genetic background may influence the nature of disease. The Jewish population in Israel is composed of Ashkenazi and Sephardic Jews, who differ in their genetic background. Previous studies have reported that the prevalence of CD in Sephardic Jews is lower than in Ashkenazi Jews; however, no information is available regarding disease characteristics in these patient populations., Goals: To assess the demographic and clinical characteristics of CD in Israeli Jewish patients., Study: We studied 189 CD patients who were observed in our department. Demographic and clinical data were collected and analyzed., Results: Forty-eight percent of the patients had ileum-only disease. Fistulizing disease was more frequently seen in ileocolonic than in ileal ( p= 0.04) or colonic ( p= 0.01) disease, whereas strictures occurred more often in ileal than in colonic disease (22% and 3%, respectively, p= 0.007). No association was found between current smoking and disease severity. Sephardic patients more frequently had extraintestinal disease than did Ashkenazi patients (35% vs. 17%, respectively, = 0.019)., Conclusion: Jewish Israeli patients show a predilection for ileum-only disease. Disease severity appears not to be influenced by smoking. These differences in disease behavior may be related to genetic factors.