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ObjectivesTo assess the difference in direct medical costs between on-demand (OD) treatment with esomeprazole (E) 20 mg and continuous (C) treatment with E 20 mg q.d. from a clinical practice view in patients with gastroesophageal reflux disease (GERD) symptoms.MethodsThis open, randomized study (ONE: on-demand Nexium evaluation) compared two long-term management options with E 20 mg in endoscopically uninvestigated patients seeking primary care for GERD symptoms who demonstrated complete relief of symptoms after an initial treatment of 4 weeks with E 40 mg. Data on consumed quantities of all cost items were collected in the study, while data on prices during the time of study were collected separately. The analysis was done from a societal perspective.ResultsForty-nine percent (484 of 991) of patients randomized to the OD regimen and 46% (420 of 913) of the patients in the C group had at least one contact with the investigator that would have occurred nonprotocol-driven. The difference of the adjusted mean direct medical costs between the treatment groups was CHF 88.72 (95% confidence interval: CHF 41.34–153.95) in favor of the OD treatment strategy (Wilcoxon rank-sum test: P < 0.0001). Adjusted direct nonmedical costs and productivity loss were similar in both groups.ConclusionsThe adjusted direct medical costs of a 6-month OD treatment with esomeprazole 20 mg in uninvestigated patients with symptoms of GERD were significantly lower compared with a continuous treatment with E 20 mg once a day. The OD therapy represents a cost-saving alternative to the continuous treatment strategy with E.

Resume Les maladies inflammatoires cryptogeniques de l’intestin resultent d’une reponse immune aberrante. Plusieurs cas de maladie inflammatoire cryptogenique de l’intestin apres transplantation d’organes tels que foie ou rein ont ete rapportes alors que ces malades prenaient des immunosuppresseurs qui sont des medicaments clefs dans le traitement des maladies inflammatoires cryptogeniques de l’intestin. Sur une serie de 120 malades suivis dans notre centre pour une transplantation hepatique, nous decrivons 4 cas de maladie inflammatoire cryptogenique de l’intestin diagnostiques apres transplantation hepatique chez des malades sous therapie immunosuppressive et sans antecedent personnel de maladie inflammatoire cryptogenique de l’intestin ou de cholangite sclerosante primitive. Trois malades ont developpe une rectocolite hemorragique sous forme de pancolite et le 4 e une maladie de Crohn. Les raisons de la transplantation hepatique etaient une cirrhose post hepatite C chez 2 malades, une cirrhose auto-immune et une cirrhose alcoolique. Dans les 4 cas, l’immunosuppression apres transplantation d’organe consistait en une monotherapie de cyclosporine. Le nombre de cas decrit dans cette serie suggere que l’immunosuppression sous forme d’une monotherapie de cyclosporine ne previent pas le developpement d’une maladie inflammatoire cryptogenique de l’intestin apres transplantation hepatique.

Despite the proven ability of immunization to prevent Helicobacter infection in mouse models, the precise mechanism of protection has remained elusive.We explored the cellular events associated with Helicobacter clearance from the stomach following vaccination by flow cytometry analysis and histological and molecular studies.Kinetic studies showed that the infection is undetectable in vaccinated mice at day 5 postbacterial challenge. Flow cytometry analysis showed that the percentages of mast cells (CD3 - CD117 + ) increased in the lymphoid cells isolated from the stomach at day 4 postchallenge in urease + cholera toxin (CT)-vaccinated mice in comparison with mice administered with CT alone (9.4% +/- 4.4% and 3.1% +/- 1%, respectively, for vaccinated and CT administered, n = 5; P.01). Quantitative PCR analysis showed an increased messenger RNA (mRNA) expression of the mast cell proteases 1 and 2 at day 5 postchallenge in the stomach of vaccinated mice. In contrast to wild-type mice, mast cell-deficient mice (W/W v mice) were not protected from H felis colonization after vaccination. Indeed only 1 out of 12 vaccinated W/W v mice showed a negative urease test. Remarkably, vaccinated W/W v mice reconstituted with cultured bone marrow-derived mast cells recovered the ability to clear the infection after vaccination (8 out of 10 mast cell-reconstituted mice showed negative urease tests [ P.006 as compared with wild-type mice]).These experiments show that mast cells are, unexpectedly, critical mediators of anti- Helicobacter vaccination.

Background & Aims: Regulation of gene expression in the follicle-associated epithelium (FAE) over Peyer's patches is largely unknown. CCL20, a chemokine that recruits immature dendritic cells, is one of the few FAE-specific markers described so far. Lymphotoxin β (LTα1β2) expressed on the membrane of immune cells triggers CCL20 expression in enterocytes. In this study, we measured expression profiles of LTα1β2-treated intestinal epithelial cells and selected CCL20 -coregulated genes to identify new FAE markers. Methods: Genomic profiles of T84 and Caco-2 cell lines treated with either LTα1β2, flagellin, or tumor necrosis factor α were measured using the Affymetrix GeneChip U133A. Clustering analysis was used to select CCL20 -coregulated genes, and laser dissection microscopy and real-time polymerase chain reaction on human biopsy specimens was used to assess the expression of the selected markers. Results: Applying a 2-way analysis of variance, we identified regulated genes upon the different treatments. A subset of genes involved in inflammation and related to the nuclear factor κB pathway was coregulated with CCL20 . Among these genes, the antiapoptotic factor TNFAIP3 was highly expressed in the FAE. CCL23 , which was not coregulated in vitro with CCL20 , was also specifically expressed in the FAE. Conclusions: We have identified 2 novel human FAE specifically expressed genes. Most of the CCL20 -coregulated genes did not show FAE-specific expression, suggesting that other signaling pathways are critical to modulate FAE-specific gene expression.

Background & Aims: Oral immunization with Helicobacter pylori urease can cure Helicobacter infection in animals. As a step toward therapeutic immunization in humans, the safety and immunogenicity of oral immunization with recombinant H. pylori urease were tested in H. pylori –infected adults. Methods: Twenty-six H. pylori –infected volunteers were randomized in a double-blind study to four weekly oral doses of 180, 60, or 20 mg of urease with 5 μg heat-labile enterotoxin of Escherichia coli (LT), LT alone, or placebo. Side effects and immune responses were evaluated weekly after immunization, and gastric biopsy specimens were obtained after 1 month and 6 months for histology and quantitative cultures. Results: Diarrhea was noted in 16 of 24 (66%) of the volunteers who completed the study. Antiurease serum immunoglobulin A titers increased 1.58-fold ± 0.37-fold and 3.66-fold ± 1.5-fold (mean ± SEM) after immunization with 60 and 180 mg urease, respectively, whereas no change occurred in the placebo ± LT groups ( P = 0.005). Circulating antiurease immunoglobulin A–producing cells increased in volunteers exposed to urease compared with placebo (38.9 ± 13.6/10 6 vs. 5.4 ± 3.1; P = 0.018). Eradication of H. pylori infection was not observed, but urease immunization induced a significant decrease in gastric H. pylori density. Conclusions: H. pylori urease with LT is well tolerated and immunogenic in H. pylori –infected individuals. An improved vaccine formulation may induce curative immunity. GASTROENTEROLOGY 1999;116:804-812

Background/Aims: Because Helicobacter pylori is a potentially dangerous human pathogen, the protective potential of oral immunization with H. pylori urease and its subunits was evaluated in an animal model. Methods: Mice were orally immunized with H. pylori sonicate, urease, or recombinant enzymatically inactive urease subunits and then challenged with Helicobacter felis . Control mice were sham-immunized. Results: H. felis colonization was present 5 days after challenge in 9 of 10 sham-immunized, 6 of 9 sonicate-immunized, and 3 of 10 urease-immunized animals ( P = 0.031 vs. sham-immunized). Twelve days after challenge, urease B-immunized mice had a weaker colonization than sham-immunized controls, whereas urease A had no effect. After 70 days, most urease A- and urease B-immunized mice had cleared the colonization (1017: P=0.0019; 1620: P=0.00002 vs. sham-immunized). In urease B-immunized animals, protection was often associated with corpus gastritis. Conclusions: Oral immunization with H. pylori urease protects mice against H. felis infection. Enzymatically inactive urease A and B subunits contain protective epitopes. It is unclear whether protection depends on the development of a mononuclear inflammatory response in the gastric corpus. Our observations should encourage the development of a human vaccine.

MDCK cells expressing the polymeric immunoglobulin (poly-Ig) receptor, cocultured with IgA-producing hybridoma cells, transported dimeric IgA (dIgA) from the basolateral into the lumenal compartment, where it was recovered as secretory component-dIgA complexes. The tail of the receptor was phosphorylated on serines 664 and 726. Each serine was mutated to alanine. Appearance of A726 receptor at the basolateral surface was reduced approximately 5-fold. This was accompanied by a approximately 5-fold reduction in dIgA transcytosis. Basolateral delivery of receptor was not affected by mutation A664, and in the absence of dIgA, the receptor accumulated in recycling basolateral endosomes. In coculture, however, dIgA transcytosis by A664 receptor was normal. Thus, entry of receptor into the transcytotic pathway requires Ser-664 phosphorylation only in the absence of dIgA.

Background: Certolizumab pegol (CTZ) is approved for the treatment of Crohn's disease (CD) in the United States and Switzerland. In view of the limited long-term data from pivotal registry trials we aimed to evaluate the efficacy and safety of CTZ in clinical long term practice in Switzerland.Methods: In the FACTS III (First Approved Certolizumab Therapeutic Experience in Switzerland) phase IV multicenter practice-based patient cohort patients receiving CTZ were prospectively included all over Switzerland in (non-) academic hospitals and private practice. Results: A total of 104 patients (52 male) were included with first CTZ dose between 11/2007-and 08/2013 with a currently ongoing follow-up of until present between 6 weeks up to 5 years (mean 67.5 weeks, CI 6-208) and baseline-characteristics as follows: mean age: 36.6 years; mean age at diagnosis: 29.4 years (Montreal A1: 8.7%, A2: 68.3%, A3: 20.2%, unknown 2.8%); disease localization L1: 13.5%, L2: 63.5%, L3: 22.1%, unknown: 1.9%; disease behavior B1: 25%, B2: 25%, B3: 47.1%, unknown: 3.9%; smokers: 33.7%; previous surgery: 44%; anti-TNF naive: 22.1%; previously received IFX, ADA orb both: 28.8%, 1.9% and 46.2%, respectively. During treatment with CTZ we observed a significant decrease of mean HBI from 8.4 at baseline to 6.1 (p=0.017), 6.1 (p= 0.063), 5.4 (p=0.002), 5.1 (p=0.009), 4.5 (p

Background: Ulcerative colitis (UC) is a chronic disease with a wide variety of treatment options many of which are not evidence based. Supplementing available guidelines, which are often broadly defined, consensus-based and generally not tailored to specifically reflect the individual patient situation, we developed explicit appropriateness criteria to assist, and improve treatment decisions. Methods: We used the RAND appropriateness method which does not force consensus. An extensive literature review was compiled based on and supplementing, where necessary, the ECCO UC 2011 guidelines. EPATUC (endorsed by ECCO) was formed by 8 gastroenterologists, 2 surgeons and 2 general practitioners from throughout Europe. Clinical scenarios reflecting practice were rated on a 9-point scale from 1 (extremely inappropriate) to 9 (extremely appropriate), based on the expert's experience and the available literature. After extensive discussion, all scenarios were re-rated at a two-day panel meeting. Median and disagreement were used to categorize ratings into 3 categories: appropriate, uncertain and inappropriate. Results: 718 clinical scenarios were rated, structured in 13 main clinical presentations: not refractory (n=64) or refractory (n=33) proctitis, mild to moderate left-sided (n=72) or extensive (n=48) colitis, severe colitis (n=36), steroid-dependant colitis (n=36), steroid-refractory colitis (n=55), acute pouchitis (n=96), maintenance of remission (n=248), colorectal cancer prevention (n=9) and fulminant colitis (n=9). Overall, 100 indications were judged appropriate (14%), 129 uncertain (18%) and 489 inappropriate (68%). Disagreement between experts was very low (6%). Conclusion: For the very first time, explicit appropriateness criteria for therapy of UC were developed that allow both specific and rapid therapeutic decision making and prospective assessment of treatment appropriateness. Comparison of these detailed scenarios with patient profiles encountered in the Swiss IBD cohort study indicates good concordance. EPATUC criteria will be freely accessible on the internet (epatuc.ch).

Background: Surgery has been previously reported to be necessary in up to 80% of Crohn's disease (CD) patients, and up to 65% of patients needed reoperation after 10 years. Prevention of surgery is therefore a particularly important issue for these patients. Treatment options are controversial and data on them are scarce. This study reports medical treatments and main clinical risk factors in CD patients having undergone one or several surgeries. Risks for being free from surgery were also assessed. Methods: Retrospective cohort study, using data from patients included in the Swiss IBD cohort study from November 2006 to July 2011. History of resective surgeries, clinical characteristics and drug regimens were collected through detailed medical records. Univariate and multivariate analyses for clinical and therapeutic factors were performed. Cox regression was made to estimate free-of-surgery risks for different phenotypes and drugs. Results: Out of 1138 CD patients in the cohort, 721 (63.4%) were free of surgery at inclusion; 203 (17.8%) had 1 surgery and 214 (18.8%) >1 surgery. Main risk factors for surgery were disease duration 5-10 years (OR=2.92; p10 years (OR=10.45; p

Despite the proven ability of immunization to reduce Helicobacter infection in mouse models, the precise mechanism of protection has remained elusive. This study explores the possibility that interleukin (IL)-17 plays a role in the reduction of Helicobacter infection following vaccination of wild-type animals or in spontaneous reduction of bacterial infection in IL-10-deficient mice.In mice, reducing Helicobacter infection, the levels and source of IL-17 were determined and the role of IL-17 in reduction of Helicobacter infection was probed by neutralizing antibodies.Gastric IL-17 levels were strongly increased in mice mucosally immunized with urease plus cholera toxin and challenged with Helicobacter felis as compared with controls (654 +/- 455 and 34 +/- 84 relative units for IL-17 messenger RNA expression [P.01] and 6.9 +/- 8.4 and 0.02 +/- 0.04 pg for IL-17 protein concentration [P.01], respectively). Flow cytometry analysis showed that a peak of CD4(+)IL-17(+) T cells infiltrating the gastric mucosa occurred in immunized mice in contrast to control mice (4.7% +/- 0.3% and 1.4% +/- 0.3% [P.01], respectively). Gastric mucosa-infiltrating CD4(+)IL-17(+) T cells were also observed in IL-10-deficient mice that spontaneously reduced H felis infection (4.3% +/- 2.3% and 2% +/- 0.6% [P.01], for infected and noninfected IL-10-deficient mice, respectively). In wild-type immunized mice, intraperitoneal injection of anti-IL-17 antibodies significantly inhibited inflammation and the reduction of Helicobacter infection in comparison with control antibodies (1 of 12 mice vs 9 of 12 mice reduced Helicobacter infection [P.01], respectively).IL-17 plays a critical role in the immunization-induced reduction of Helicobacter infection from the gastric mucosa.

BODY: Introduction: Biological therapy has dramatically changed the management of Crohn's disease (CD). Appropriateness criteria for maintenance treatment after medically-induced remission (MIR) or surgically-induced remission (SIR) of CD have thus been updated. Formal evidence is weak formany therapeutic decisions regardingmaintenance treatment for CD and thus clinically-explicit and situation-tailored criteria made freely available on the internet will be helpful to physicians in daily decision-making in clinical practice. Methods: Multidisciplinary international experts (EPACT II, Geneva, Switzerland) discussed and anonymously rated virtual clinical indications on the basis of evidence in the literature. Median ratings (on a 9-point scale) were stratified according to three assessment categories: appropriate (7-9), uncertain (4-6 and/or disagreement) and inappropriate (1-3). Experts were also asked to rank appropriate medication according to their own clinical practice, without any consideration of cost. Results: 392 specific indications for maintenance treatment of CD were rated (200 for MIR and 192 for SIR). Azathioprine, methotrexate and/ or anti-TNF antibodies were considered appropriate in 42 indications, corresponding to 68% of all appropriate interventions (97% ofMIR and 39%of SIR). The remaining appropriate interventions consisted of mesalazine and a “wait-and-see” strategy. Factors that influenced the panel's voting were patient characteristics and outcome of previous treatments. Results favor the use of anti-TNF agents after one failure of any immunosuppressive therapy, while an earlier use is still controversial. Conclusion: Detailed explicit appropriateness criteria have been updated for maintenance treatment of CD. New expert recommendations for the use of the classic immunomodulators as well as anti-TNF agents are now available (www.epact.ch). The validity of these criteria should now be tested by prospective evaluation. A-173 AGA Abstracts S1029 Clinical Use and Outcomes from IBD Serology Testing in a Tertiary Referral Center Alan C. Moss, Adam Cheifetz, Nabeel Chaudhary, Jahvari Junior Background Testing for a combination of antibodies against ASCA, ANCA, and OmpC has become common-place in IBD practice. Patient selection for testing, and the impact of test results on patient management, remain variable. Aims To describe patient selection for IBD antibody testing in a tertiary referral center. To measure changes in management after test results became available. To compare test results between patient sub-groups. Methods Review of electronic medical records of all patients who completed IBD serology testing (Prometheus) at a single institution. Results Data were available on 213 patients who completed testing. The distribution of pre-testing diagnoses were as follows; no diagnosis 41 (19%), Crohn's disease 49 (23%), ulcerative colitis 60 (28%), IBD unclassified 60 (28%). In those with established IBD, 122 (57%) had colonic disease only, 36 (17%) had small bowel disease only, 13 (6%) had ileo-colonic disease, and 10 (5%) had pouchitis. The prevalence of elevated antibodies to ASCA, ANCA and OmpC in different patient populations can be seen in Table 1. The proportion of patients with a change in diagnosis after antibody testing in each patient sub-group was as follows; no diagnosis 27%, Crohn's disease 48%, ulcerative colitis 20%, IBD unclassified (IBDU) 63%. The odds ratio of a change in diagnosis after testing positive for ASCA, ANCA or OmpC was not statistically significant in any patient sub-group. A cohort of patients also underwent antibody testing for celiac disease antibodies (n=21), but all were negative. Conclusions IBD serology testing was applied to a wide range of patient populations in this center. ASCA antibodies were present in similar proportions across all patient populations. Patients with IBDU were most likely to have a change in diagnosis after antibody testing.

Introduction: Higher 6-tioguanine nucleotide (6TGN) concentrations have been related to higher probabilities of achieving clinical remission on thiopurinic therapy, but that has been hardly applied to clinical practice. Aims: To establish the utility of systematic determination of 6TGN as a marker or predictor of AZA/mercaptopurine (MP) efficacy in IBD patients. Methods: Prospective, multicenter study. Serum 6TGN and 6-methylmercaptopurine ribonucleotides (6MMPR) levels of patients starting AZA/MP for steroid dependence or resistance were periodically monitored during steroid tapering and, after withdrawal, until a new activity flare (persistence of steroid resistance or dependence), or for 6 months in those showing maintenance of clinical response. Thiopurine methyl-transferase (TPMT) activity above 5 U/ml was required. Results: 153 patients were included, and 140 finished the study. Mean age was 36 years (range 16-77), 50% were males, and 72% had Crohn's disease. Mean 6TGN levels (and the ratios 6TGN/6MMPR, 6TGN/TPMT) obtained at basal, 2 weeks, and 1, 2, 4 and 6 months after steroid withdrawal were not significantly different between patients that were or were not in clinical remission at each visit. The area under the ROC curve (AUC) evaluating the accuracy of 6TGN levels for the diagnosis of clinical response for each monitoring point was less than 0.7. No cut-off point with useful sensitivity/specificity values was found, including 230 or 260 pmol/8 x 108 (that are commonly proposed in the literature). The AUC assessing the accuracy of the 6TGN determination at 2 weeks, 1, 2 or 4 months after starting AZA/MP to predict the response by the end of the follow-up was also less than 0.7. Once again, no useful cut-off point was found. Thiopurinic-related toxicity was detected in 9 cases (6.4%): No cases of hepatotoxicity were found, and only 3 cases of myelotoxicity were reported. No differences in 6TGN levels were found in patients suffering AZA-related toxicity. Specifically, 6TGN levels could not be related to the risk of developing myelotoxicity. Conclusions: Systematic quantification of thiopurinic metabolites (6TGN/ 6MMPR) in IBD patients receiving AZA/MP with the aim of predicting or assessing treatment response or safety cannot be recommended.

Introduction: Biological therapy has dramatically changed management of Crohn's disease (CD). New data have confirmed the benefit and relative long-term safety of anti-TNFα inhibition as part of a regular scheduled administration programme. The EPACT appropriateness criteria for maintenance treatment after medically-induced remission (MIR) or surgically-induced remission (SIR) of CD thus required updating. Methods: A multidisciplinary international expert panel (EPACT II, Geneva, Switzerland) discussed and anonymously rated detailed, explicit clinical indications based on evidence in Abbreviations: CD, Crohn's Disease; 5-ASA, mesalazine and other aminosalicylates; AZA, azathioprine; 6MP, 6-mercaptopurine; MTX, methotrexate; TNFα, Tumor Necrosis Factor alpha; MIR, Medically-Induced Remission; SIR, Surgically-Induced Remission; RCT, Randomized

Introduction En novembre 2006, les six Centres Hospitaliers Universitaires (Bâle, Berne, Geneve, Lausanne, Saint-Gall et Zurich) du territoire suisse ont debute, dans leurs zones geographiques d’influence, le recrutement de patients atteints de maladies inflammatoires chroniques de l’intestin (MICI). Cet effort combine des gastro-enterologues hospitaliers et en pratique privee beneficie du soutien financier du Fond National Suisse de la recherche scientique (fonds N° 3347CO-08792/1) consecutivement aux bons resultats de l’etude pilote initiee en 2004 [1]. Les premiers resultats de cette nouvelle etude de cohorte prospective nationale vous sont presentes apres 15 mois d’activite. Patients et Methodes Sur la base de criteres diagnostiques bien etablis, les patients MICI sont inclus dans l’etude observationnelle. Les donnees epidemiologiques et cliniques sont alors collectees a l’aide d’un questionnaire rempli par le gastro-enterologue traitant avec la collaboration de l’infirmiere de recherche dont le role majeur reside dans la recolte d’echantillons biologiques. Le questionnaire est transmis systematiquement a un organe central (Data centre). Resultats 1 039 patients ont ete inclus sur 15 mois et 959 questionnaires envoyes au Data centre, correspondant respectivement a 567 maladies de Crohn, 363 rectocolites hemorragiques (RCH) et 29 colites indeterminees. Les femmes atteintes de Crohn etaient plus representees que les hommes, tandis que l’inverse etait observe pour les RCHs. Les patients Crohns avaient en moyenne 30 ans (± 14) au moment du diagnostic contre 34 ans (± 13) pour les RCHs. Parmi le groupe Crohn, l’atteinte inflammatoire se trouvait dans 27 % des cas dans l’ileon uniquement et egalement etendue au colon (ileo-colique) dans 30 % des cas, tandis que 27 % des lesions ont ete rapportees dans le colon seulement. 11 % des patients etaient en remission endoscopique. Pour les RCHs documentees, 12 % presentaient une proctite, 37 % une colite gauche et 36 % une pancolite avec 4 % d’atteinte ileale concomitante. Seuls 2 % des patients inclus avaient ete colectomises. Des complications, tels que fistules et stenoses (anciennes ou actuelles) ont ete decrites pour respectivement 34 % et 32 % des patients Crohn, alors qu’elles etaient pratiquement inexistantes chez les RCHs. Concernant le traitement a l’inclusion ; les thiopurines etaient utilisees chez 50 % et 40 % des patients atteints de Crohn et de RCH. Pour l’infliximab, ces valeurs atteignaient 24 % et 8 %, tandis que le methotrexate etait administre respectivement a 12 % des patients Crohns et 3 % des RCHs. Ces derniers etaient frequemment traites par 5ASA (72 %, contre 21 % des patients Crohns). Conclusion Les caracteristiques des patients de la Cohorte Suisse des Maladies Inflammatoires Intestinales Chroniques presentent de nombreuses similitudes avec l’etude pilote (1) et confirment une augmentation significative de l’utilisation des thiopurines et des anticorps anti-TNF. Il est necessaire a ce stade d’evaluer prospectivement l’influence de ces therapies sur l’evolution de la maladie, ainsi que leur utilisation adequate http://www.epact.ch .

Introduction Chez les patients ayant une poussee severe de rectocolite hemorragique (RCH) corticoresistante, la colectomie est actuellement preconisee en cas d’echec d’une deuxieme ligne de traitement par ciclosporine (CIS) ou infliximab (IFX). Le recours a une troisieme ligne de traitement medical n’est pas recommande (Consensus ECCO 2008) depuis la publication d’une serie de 19 patients chez lesquels le taux d’echec etait de 42 %, avec des effets secondaires serieux chez 15 % des patients, dont un deces [1, 2]. Nous rapportons dans ce travail retrospectif une plus large serie de patients traites successivement par ciclosporine et infliximab, ou inversement. Patients et Methodes Les cas de RCH ou de colite indeterminee (CI) traites successivement par CIS et IFX, ou inversement, ont ete collectes dans les centres du GETAID. Les criteres d’inclusion etaient un delai entre les deux traitements de moins d’un mois lorsque la CIS etait utilisee en premier (groupe CIS-IFX) et de moins de 2 mois dans le cas inverse (groupe IFX-CIS), un traitement par au moins une perfusion d’IFX et au moins 2 jours continus de CIS, et un suivi d’au moins 3 mois. La survie sans colectomie et les effets secondaires etaient etudies. Resultats Quatre-vingt six patients (âge median 34 ans, 49 hommes, 71 RCH et 15 CI) ont ete traites dans 16 des 36 centres GETAID entre 2000 et 2008 (0 - 24 patients par centre) ; 28 d’entre eux (33 %) avaient refuse la colectomie apres l’echec de la deuxieme ligne de traitement. Soixante-cinq patients (76 %) appartenaient au groupe CIS-IFX [delai median entre CIS et IFX : 2 jours (0 - 30)] et 21 patients (24 %) au groupe IFX-CIS [delai median entre la derniere perfusion d’IFX et CIS : 17 jours (0 - 58)]. Des corticoides et un immunosuppresseur (azathioprine/6-mercaptopurine ou methotrexate) etaient associes chez 74 (86 %) et 68 (79 %) patients. La probabilite de colectomie etait de 39 % a 3 mois, de 59 % a 1 an, et de 63 % a 3 ans (Kaplan-Meier). Le seul facteur associe a l’absence de colectomie etait l’association a l’azathioprine. Un patient âge de 45 ans (groupe CIS-IFX) est decede en post-operatoire d’une embolie pulmonaire. Trente-deux complications ont ete rapportees (dont 9 en postoperatoire) chez 23 patients, incluant 17 infections (5 en postoperatoire). Il n’existait pas un effet de sequence (IFX-CIS ou CIS-IFX) concernant l’efficacite a 3 mois et le taux de complications. Conclusion Chez les patients ayant une poussee severe de RCH en echec d’une deuxieme ligne de traitement par ciclosporine ou infliximab, une troisieme ligne a evite la colectomie chez 61 % des patients a 3 mois mais a plus long terme, chez seulement 1/3 des patients. Notre etude ne permettait pas de privilegier une sequence par rapport a l’autre. La mortalite etait de 1 % ; le taux de complications atteignait 27 % mais ne semblait pas superieur a celui rapporte dans la litterature chez les malades n’ayant recu que deux lignes de traitement medical.

BACKGROUND: Sub-occlusions are frequent complications of Crohn's disease (CD). They are usually caused by stenosis, which can be due to recurrent CD or ischemic anastomosis. Through-the-scope balloon dilation (TTS) is the only alternative to intestinal resection or stricturoplasty for the treatment of intestinal strictures. Previous studies have reported a long-term symptomatic benefit of TTS balloon dilation in CD ranging from 48% and 66%. The aim of this study is to evaluate safety and efficacy of repeated TTS balloon dilations in CD strictures. PATIENTS AND METHODS: We retrospectively analyzed consecutive endoscopy protocols of all CD patients who underwent colonoscopy or rectosigmoidoscopy with TTS balloon dilation between 2000 and 2007, in the hospital databases of University Hospital of Lausanne and Kantonspital St Gallen, Switzerland. All patients had histologically proven CD that did not improve under medical CD treatment, including 5-amino salicylic acid, azathioprine, 6-mercaptopurine, methotrexate, budesonide, prednisone or anti-TNFα. Hydrostatic TTS balloon dilation was performed using Wilson Cook/Boston Scientific balloons progressively inflated to maximal pressure for 60 seconds. RESULTS: Sixty-one consecutive patients (33 females, 28 males), mean age 37±11 years, underwent dilation for a total of 237 dilations. Mean balloon diameter was 18mm (range 10-25mm). An inflammatory activity was observed in 75% of strictures, 129 dilations were performed on anastomotic strictures (54%), the other dilations were performed on surgically naive bowel (21 in terminal ileum, 11 at the ileo-cecal valve,4 in the right colon, 21 in the left colon, 51 in the rectoanal region). Mean number of dilations was 2.25 (interval range 1 to 21) per stricture. All patients had symptoms relief post dilation, mean time before repeated dilation was 132 days (range: 3-1495 days). One perforation occured, which required surgery. CONCLUSION: TTS balloon dilation is a safe and effective treatment of CD strictures. It can be used to treat anastomotic as well as disease-induced stenosis, independently of inflammatory status. Multiple TTS balloon dilations of the same stenosis is often required to improve symptoms. Repeated TTS dilations did not increase the risk of complications.