Jean-Frédéric Colombel

Publications of Jean-Frédéric Colombel

• Long-term outcome after first intestinal resection in pediatric-onset Crohn's disease: A population-based study.

  Authors: Médina Boualit, Julia Salleron, Dominique Turck, Mathurin Fumery, Guillaume Savoye, Jean-Louis Dupas, Eric Lerebours, Alain Duhamel, Véronique Merle, Antoine Cortot, Jean-Frédéric Colombel, Laurent Peyrin-Biroulet, Corinne Gower-Rousseau

  Inflammatory bowel diseases. 05/2012;

  BACKGROUND: To describe long-term postoperative evolution of pediatric-onset Crohn's disease (CD) and identify predictors of outcome we studied a population-based cohort (1988-2004) of 404 patientsBACKGROUND: To describe long-term postoperative evolution of pediatric-onset Crohn's disease (CD) and identify predictors of outcome we studied a population-based cohort (1988-2004) of 404 patients (0-17 years), of which 130 underwent surgery. METHODS: Risks for a second resection and first need for immunosuppressors (IS) and/or biologics were estimated by survival analysis and Cox models used to determine predictors of outcome. Impact of time of first surgery on nutritional catch-up was studied using regression. RESULTS: In all, 130 patients (70 females) with a median age at diagnosis of 14.2 years (interquartile range: 12-16) were followed for 13 years (9.4-16.6). Probability of a second resection was 8%, 17%, and 29% at 2, 5, and 10 years, respectively. In multivariate analysis, age <14, stenosing (B2) and penetrating (B3) behaviors and upper gastrointestinal location (L4) at diagnosis were associated with an increased risk of second resection. Probability of receiving IS or biologics was 18%, 34%, and 47% at 2, 5, and 10 years, respectively. In multivariate analysis, L4 was a risk factor for requiring IS or biologics, while surgery within 3 years after CD diagnosis was protective. Catch-up in height and weight was better in patients who underwent surgery within 3 years after CD diagnosis than those operated on later. CONCLUSIONS: In this pediatric-onset CD study, mostly performed in a prebiologic era, a first surgery performed within 3 years after CD diagnosis was associated with a reduced need for IS and biologics and a better catch-up in height and weight compared to later surgery. (Inflamm Bowel Dis 2012;).

• Immunosuppression in inflammatory bowel disease: how much is too much?

  Authors: Benjamin L Cohen, Joana Torres, Jean-Frédéric Colombel

  Current opinion in gastroenterology. 05/2012;

  PURPOSE OF REVIEW: Current treatment approaches favor the early introduction of immunomodulators and/or antitumor necrosis factor (TNF) agents. There is now strong evidence showing that combinationPURPOSE OF REVIEW: Current treatment approaches favor the early introduction of immunomodulators and/or antitumor necrosis factor (TNF) agents. There is now strong evidence showing that combination therapy appears to be more effective than monotherapy in both ulcerative colitis and Crohn's disease. However, there are concerns associated with this strategy, and eventually the following questions will emerge when discussing therapeutic options with our patients: is it safe to maintain these therapies for the long-term?; how long should we maintain therapy?; and if we decide to stop or de-escalate therapy, what strategy should we use? RECENT FINDINGS: During the past year new evidence regarding safety of long-term therapy with anti-TNF and immunomodulators, and predictors of relapse following therapy discontinuation have become available. SUMMARY: In this review we aim to discuss some of the safety concerns related to the use of immunosuppressive drugs used in inflammatory bowel disease, as well as the possible strategy for de-escalation or discontinuation therapy. Eventually, choosing to stop either the anti-TNF or the immunomodulator is a case-by-case decision based on the estimated risk-benefit ratio. In addition to the identified predictors of relapse after therapy discontinuation, other considerations such as long-term safety, cost, and natural history of the disease must be brought into this discussion.

• Immunohistochemical search for viral and bacterial antigens in Crohn's disease.

  Authors: William S Magin, Herbert J Van Kruiningen, Jean-Frédéric Colombel

  Journal of Crohn's & colitis. 04/2012;

  BACKGROUND: Recent studies show that diseased intestinal tissues of patients with Crohn's disease (CD) contain obstructed lymphatics, granulomas, and tertiary lymphoid organs, representing responsesBACKGROUND: Recent studies show that diseased intestinal tissues of patients with Crohn's disease (CD) contain obstructed lymphatics, granulomas, and tertiary lymphoid organs, representing responses to persistent antigen. METHODS: Forty-seven tissue sections from 28 CD patients and 20 tissue sections from 17 control patients were studied. Tissues were immunostained with antibody directed against adenovirus, Epstein-Barr virus, herpes simplex virus I, parvovirus B19, Listeria monocytogenes, Escherichia coli, Clostridium perfringens, and Mycobacterium avium subspecies paratuberculosis. RESULTS: There was no evidence of adenovirus, Epstein-Barr virus, parvovirus B19, or M. avium subsp. paratuberculosis in the tissues. Clostridia were positively stained in the mucus of 18.5% of CD patients versus 35.3% of controls and in the tissue of 11.1% of CD patients but in no controls. Immunoreactivity to listeria antibody occurred in the mucus of 3.7% of CD patients and in 5.9% of controls while it occurred in the tissue of 37.0% of CD patients and 29.4% of controls. E. coli occurred in the mucus of 48.1% CD and 64.7% controls and in the tissue of 18.5% and 5.9% respectively. CONCLUSIONS: Of the agents demonstrated in this search, none was located in granulomas or inflamed lymphatics. Finding the common gut microbes, E. coli and clostridia, in the mucus of patients and controls was not unexpected. The minor focal staining of E. coli and clostridia does not suggest a primary role for these pathogens in CD. Positive staining for listeria in patients and controls may very well represent cross reactivity rather than specific identification.

• Endoscopic improvement of mucosal lesions in patients with moderate to severe ileocolonic Crohn's disease following treatment with certolizumab pegol.

  Authors: Xavier Hébuterne, Marc Lémann, Yoram Bouhnik, Olivier Dewit, Jean-Louis Dupas, Michael Mross, Geert D'Haens, Krassimir Mitchev, Etienne Ernault, Séverine Vermeire, Hedia Brixi-Benmansour, Tom G Moreels, Jean-Yves Mary, Philippe Marteau, Jean-Frédéric Colombel

  Gut. 04/2012;

  ObjectiveTo evaluate the efficacy of certolizumab pegol (CZP) in improving endoscopic lesions in patients with active ileocolonic Crohn's disease (CD).MethodsThis phase IIIB multicentre open-labelObjectiveTo evaluate the efficacy of certolizumab pegol (CZP) in improving endoscopic lesions in patients with active ileocolonic Crohn's disease (CD).MethodsThis phase IIIB multicentre open-label clinical trial enrolled 89 adult patients with active endoscopic disease (ulceration in ≥2 intestinal segments with a Crohn's Disease Endoscopic Index of Severity (CDEIS) score ≥8 points). Patients received subcutaneous CZP 400 mg at weeks 0, 2 and 4 and every 4 weeks up to week 52. Endoscopic evaluations were performed at weeks 0, 10 and 54. The primary outcome was mean change in CDEIS score at week 10; secondary outcome measures included endoscopic response (decrease in CDEIS score >5 points), remission (CDEIS score <6), complete remission (CDEIS score <3) and mucosal healing (no ulcer) at weeks 10 and 54.ResultsIn the intention-to-treat population (n=89) the mean±SD CDEIS score was 14.5±5.3 at baseline; the mean decrease in CDEIS score at week 10 was 5.7 (95% CI 4.6 to 6.8, p<0.0001). Rates of endoscopic response, endoscopic remission, complete endoscopic remission and mucosal healing at week 10 were 54%, 37%, 10% and 4%, respectively. At week 54 the corresponding rates were 49%, 27%, 14% and 8%, respectively. The safety profile was consistent with that of previous CZP trials.ConclusionsFollowing CZP treatment in patients with active CD, endoscopic lesions were improved as shown by the decrease in mean CDEIS score and by endoscopic response and remission rates. These benefits were achieved as early as week 10 and were generally maintained through week 54.Clinical Trial Registration NumberNCT00297648.

• Developing an instrument to assess the endoscopic severity of ulcerative colitis: the Ulcerative Colitis Endoscopic Index of Severity (UCEIS).

  Authors: Simon P L Travis, Dan Schnell, Piotr Krzeski, Maria T Abreu, Douglas G Altman, Jean-Frédéric Colombel, Brian G Feagan, Stephen B Hanauer, Marc Lémann, Gary R Lichtenstein, Phillippe R Marteau, Walter Reinisch, Bruce E Sands, Bruce R Yacyshyn, Christian A Bernhardt, Jean-Yves Mary, William J Sandborn

  Gut. 04/2012; 61(4):535-42.

  Background Variability in endoscopic assessment necessitates rigorous investigation of descriptors for scoring severity of ulcerative colitis (UC). Objective To evaluate variation in the overallBackground Variability in endoscopic assessment necessitates rigorous investigation of descriptors for scoring severity of ulcerative colitis (UC). Objective To evaluate variation in the overall endoscopic assessment of severity, the intra- and interindividual variation of descriptive terms and to create an Ulcerative Colitis Endoscopic Index of Severity which could be validated. Design A two-phase study used a library of 670 video sigmoidoscopies from patients with Mayo Clinic scores 0-11, supplemented by 10 videos from five people without UC and five hospitalised patients with acute severe UC. In phase 1, each of 10 investigators viewed 16/24 videos to assess agreement on the Baron score with a central reader and agreed definitions of 10 endoscopic descriptors. In phase 2, each of 30 different investigators rated 25/60 different videos for the descriptors and assessed overall severity on a 0-100 visual analogue scale. κ Statistics tested inter- and intraobserver variability for each descriptor. A general linear mixed regression model based on logit link and β distribution of variance was used to predict overall endoscopic severity from descriptors. Results There was 76% agreement for 'severe', but 27% agreement for 'normal' appearances between phase I investigators and the central reader. In phase 2, weighted κ values ranged from 0.34 to 0.65 and 0.30 to 0.45 within and between observers for the 10 descriptors. The final model incorporated vascular pattern, (normal/patchy/complete obliteration) bleeding (none/mucosal/luminal mild/luminal moderate or severe), erosions and ulcers (none/erosions/superficial/deep), each with precise definitions, which explained 90% of the variance (pR(2), Akaike Information Criterion) in the overall assessment of endoscopic severity, predictions varying from 4 to 93 on a 100-point scale (from normal to worst endoscopic severity). Conclusion The Ulcerative Colitis Endoscopic Index of Severity accurately predicts overall assessment of endoscopic severity of UC. Validity and responsiveness need further testing before it can be applied as an outcome measure in clinical trials or clinical practice.

• Reply.

  Authors: Edouard Louis, Jean-Yves Mary, Jean-Frédéric Colombel

  Gastroenterology. 03/2012;

• Replication of Crohn's disease-associated AIEC within macrophages is dependent on TNF-α secretion.

  Authors: Marie-Agnès Bringer, Elisabeth Billard, Anne-Lise Glasser, Jean-Frédéric Colombel, Arlette Darfeuille-Michaud

  Laboratory investigation; a journal of technical methods and pathology. 03/2012; 92(3):411-9.

  Adherent and invasive Escherichia coli (AIEC) associated with Crohn's disease are able to survive and to replicate extensively in active phagolysosomes within macrophages. AIEC-infected macrophagesAdherent and invasive Escherichia coli (AIEC) associated with Crohn's disease are able to survive and to replicate extensively in active phagolysosomes within macrophages. AIEC-infected macrophages release large amounts of tumour necrosis factor-alpha (TNF-α) and do not undergo cell death. The aim of the present study was to determine what benefit AIEC bacteria could gain from inducing the release of large amounts of TNF-α by infected macrophages and to what extent the neutralization of TNF-α could affect AIEC intramacrophagic replication. Our results showed that the amount of TNF-α released by infected macrophages is correlated with the load of intramacrophagic AIEC bacteria and their intracellular replication. TNF-α secretion was not related to the number of bacteria entering host cells because when the number of bacteria internalized in macrophage was decreased by blocking lipid raft-dependent and clathrin-coated pits-dependent endocytosis, the amount of TNF-α secreted by infected macrophages was not modified. Interestingly, dose-dependent increases in the number of intracellular AIEC LF82 bacteria were observed when infected macrophages were stimulated with exogenous TNF-α, and neutralization of TNF-α secreted by AIEC-infected macrophages using anti-TNF-α antibodies induced a significant decrease in the number of intramacrophagic bacteria. These results indicate that AIEC bacteria use TNF-α as a Trojan horse to ensure their intracellular replication because replication of AIEC bacteria within macrophages induces the release of TNF-α, which in turn increases the intramacrophagic replication of AIEC. Neutralizing TNF-α secreted by infected macrophages may represent an effective strategy to control AIEC intracellular replication.

• Adalimumab Induces and Maintains Mucosal Healing in Patients With Crohn's Disease: Data From the EXTEND Trial.

  Authors: Paul Rutgeerts, Gert Van Assche, William J Sandborn, Douglas C Wolf, Karel Geboes, Jean-Frédéric Colombel, Walter Reinisch, Ashish Kumar, Andreas Lazar, Anne Camez, Kathleen G Lomax, Paul F Pollack, Geert D'haens

  Gastroenterology. 02/2012;

  BACKGROUND & AIMS: We investigated the efficacy of adalimumab for inducing and maintaining mucosal healing in patients with Crohn's disease (CD). METHODS: A randomized, double-blind,BACKGROUND & AIMS: We investigated the efficacy of adalimumab for inducing and maintaining mucosal healing in patients with Crohn's disease (CD). METHODS: A randomized, double-blind, placebo-controlled trial (extend the safety and efficacy of adalimumab through endoscopic healing [EXTEND]) evaluated adalimumab for induction and maintenance of mucosal healing in 135 adults with moderate to severe ileocolonic CD. The baseline degree of mucosal ulceration was documented by ileocolonoscopy. All patients received induction therapy (subcutaneous adalimumab 160/80 mg at weeks 0/2). At week 4, patients were randomly assigned to groups given 40 mg adalimumab or placebo every other week through week 52. Open-label adalimumab was given to patients with flares or no response, starting at week 8. Mucosal healing was reassessed by ileocolonoscopy at weeks 12 and 52. RESULTS: Twenty-seven percent of patients receiving adalimumab had mucosal healing at week 12 (the primary end point) versus 13% given placebo (P = .056). At week 52, rates of mucosal healing were 24% and 0, respectively (P < .001). Remission rates, based on the Crohn's Disease Endoscopic Index of Severity, were 52% for adalimumab and 28% for placebo at week 12 (P = .006) and 28% and 3%, respectively, at week 52 (P < .001). Rates of clinical remission based on the Crohn's Disease Activity Index were greater among patients given continuous adalimumab therapy versus placebo at weeks 12 (47% vs 28%; P = .021) and 52 (33% vs 9%; P = .001). Five serious (1 during induction and 4 during open-label therapy) and 3 opportunistic infections (1 in each group during double-blind therapy and 1 during open-label therapy) were reported (n = 135). CONCLUSIONS: Following induction therapy with adalimumab, patients with moderately to severely active CD who continue to receive adalimumab are more likely to achieve mucosal healing than those given placebo.

• Physician perspectives on unresolved issues in the use of conventional therapy in Crohn's disease: results from an international survey and discussion programme.

  Authors: Marc Ferrante, Konstantinos Karmiris, Evan Newnham, Jesse Siffledeen, Zuzana Zelinkova, Gert van Assche, Peter L Lakatos, Julian Panés, Andreas Sturm, Simon Travis, C Janneke van der Woude, Walter Reinisch, Jean-Frédéric Colombel, Remo Panaccione

  Journal of Crohn's & colitis. 02/2012; 6(1):116-31.

  Data on the optimal use of conventional therapies in Crohn's disease are lacking in guidelines. An educational programme was established to explore questions raised in clinical practice and toData on the optimal use of conventional therapies in Crohn's disease are lacking in guidelines. An educational programme was established to explore questions raised in clinical practice and to provide practical answers. Telephone interviews with 96 gastroenterologists and a web survey of 1370 gastroenterologists identified 26 key questions. Ten questions were taken forward to the next stage based on the opinion of an International Steering Committee. Draft answers to the questions were prepared from available evidence following a literature search. The draft answers were debated in national meetings of participating countries (n=36) and voted on using a standard scoring system. Revised answers went forward to an international meeting and were debated and voted on using the same methodology. Final answers were developed, based on evidence and clinical experience of the participants. Evidence on corticosteroid and immunomodulator use such as dosage, timing and duration, choice of drug or regimen, and safety is scarce. Key points of the answers included the importance of: identifying patients with poor prognosis; early intervention with optimal doses of immunomodulators; avoiding prolonged or repetitive corticosteroid therapy; achieving corticosteroid-free remission; achieving a balance between clinical benefit and safety when intensifying or prolonging therapy or combining different agents; re-evaluating therapy at appropriate time points; and considering the role of biomarkers and mucosal healing. The answers to 10 key questions were based on available evidence and clinical experience of programme participants. It is hoped they will be of practical use in everyday gastroenterology practice.

• Changing Crohn's disease management: Need for new goals and indices to prevent disability and improve quality of life.

  Authors: Daniel Hommes, Jean-Frédéric Colombel, Paul Emery, Marco Greco, William J Sandborn

  Journal of Crohn's & colitis. 02/2012; 6 Suppl 2:S224-34.

  Crohn's disease is a destructive, inflammatory condition. The recent IMPACT survey showed that it has a major impact on quality of life including fatigue, relationships and employment. AlthoughCrohn's disease is a destructive, inflammatory condition. The recent IMPACT survey showed that it has a major impact on quality of life including fatigue, relationships and employment. Although patients are generally satisfied with healthcare services, improvements are needed in the timeliness of diagnosis and in communication between patients and healthcare professionals. Evidence is lacking about what constitutes quality of care and value to patients. Moving forward, value should become the primary goal of healthcare delivery, which is likely to require new treatment goals. Indeed, goals are already evolving beyond symptom control towards deep remission, which encompasses clinical remission together with mucosal healing. The ultimate goals are to prevent bowel damage, reduce long-term disability and maintain normal quality of life. A new treat-to-target approach, with increased monitoring and tighter control of symptoms and inflammation, will be needed. This approach will be enabled by use of biomarkers and new indices such as the Lémann score, which assesses the extent and severity of bowel damage at a specific time-point and over time, and a new disability index for patients with inflammatory bowel disease. These principles have been adopted for managing rheumatoid arthritis where there is now a focus on treat-to-target to achieve early remission. Lessons from rheumatoid arthritis can be translated to Crohn's disease.

• Therapeutic drug monitoring of biologics for inflammatory bowel disease.

  Authors: Jean-Frédéric Colombel, Brian G Feagan, William J Sandborn, Gert Van Assche, Anne M Robinson

  Inflammatory bowel diseases. 02/2012; 18(2):349-58.

  Although tumor necrosis factor (TNF) antagonists are effective for the treatment of Crohn's disease and ulcerative colitis, lack and loss of clinical response is a clinical challenge. Accordingly,Although tumor necrosis factor (TNF) antagonists are effective for the treatment of Crohn's disease and ulcerative colitis, lack and loss of clinical response is a clinical challenge. Accordingly, the use of therapeutic drug monitoring has been proposed as a means to optimize treatment. This article reviews the mechanisms of and factors which influence clearance of biologics, the relationship between serum drug concentrations and antidrug antibody presence and treatment efficacy, and identifies areas for future research needs regarding the use of therapeutic drug monitoring in clinical practice. Publications regarding these topics were identified from literature searching and supplemented by review of gastroenterology meeting presentations and reference lists. The clearance of monoclonal antibodies and pegylated antibody fragments is complex, and may be affected by demographic variables, concomitant medications, inflammatory burden, and immunogenicity, leading to high interpatient variability in plasma concentration of drug and clinical response. Several observational studies have demonstrated a relationship between anti-TNF agent serum drug concentrations and/or antidrug antibody presence and various symptomatic and objective clinical endpoints. However, these relationships are not absolute, and although some algorithms for the use of therapeutic drug monitoring in clinical practice have been proposed, none have yet been validated in a prospective clinical trial. Further research to identify the most appropriate use of therapeutic drug monitoring is needed.

• Risk factors of anxiety and depression in inflammatory bowel disease.

  Authors: Stéphane Nahon, Pierre Lahmek, Christelle Durance, Alain Olympie, Bruno Lesgourgues, Jean-Frédéric Colombel, Jean-Pierre Gendre

  Inflammatory bowel diseases. 01/2012;

  BACKGROUND: Little is known in inflammatory bowel disease (IBD) regarding risk factors for psychological distress. The aim of this work was to study the disease characteristics and socioeconomicBACKGROUND: Little is known in inflammatory bowel disease (IBD) regarding risk factors for psychological distress. The aim of this work was to study the disease characteristics and socioeconomic factors associated with anxiety and depression in IBD. METHODS: From December 2008 to June 2009, 1663 patients with IBD (1450 were members of the Association Francois Aupetit, French association of IBD patients) answered a questionnaire about psychological and socioeconomic factors and adherence to treatment. In this study we focused the analysis on the characteristics of IBD (type, location, severity, treatment) and socioeconomic factors (professional, educational, and marital status and Evaluation of Precarity and Inequalities in Health Examination Centers [EPICES] score of socioeconomic deprivation; score established in medical centers in France; http://www.cetaf.asso.fr) associated with depression and anxiety. Anxiety and depression were assessed by the Hospital Anxiety and Depression Scale. Comparison between groups according to the existence of depression or anxiety was carried out using univariate and multivariate analysis. RESULTS: In all, 181 patients (11%) were depressed; 689 patients (41%) were anxious. By multivariate analysis, factors associated with anxiety were: severe disease (P = 0.04), flares (P = 0.05), nonadherence to treatment (P = 0.03), disabled or unemployed status (P = 0.002), and socioeconomic deprivation (P < 0.0001). Factors associated with depression were: age (P = 0.004), flares (P = 0.03), disabled or unemployed status (P = 0.03), and socioeconomic deprivation (P < 0.0001). CONCLUSIONS: In this large cohort of IBD patients, risk factors for anxiety and depression were severe and active disease and socioeconomic deprivation. Psychological interventions would be useful when these factors are identified. (Inflamm Bowel Dis 2012;).

• Clinical predictors at diagnosis of disabling pediatric Crohn's disease.

  Authors: Guillaume Savoye, Julia Salleron, Corinne Gower-Rousseau, Jean-Louis Dupas, Gwénola Vernier-Massouille, Mathurin Fumery, Véronique Merle, Eric Lerebours, Antoine Cortot, Dominique Turck, Jean-Louis Salomez, Marc Lemann, Jean-Frédéric Colombel, Alain Duhamel

  Inflammatory bowel diseases. 01/2012;

  BACKGROUND: Identification of children with Crohn's disease (CD) at high risk of disabling disease would be invaluable in guiding initial therapy. Our study aimed to identify predictors at diagnosisBACKGROUND: Identification of children with Crohn's disease (CD) at high risk of disabling disease would be invaluable in guiding initial therapy. Our study aimed to identify predictors at diagnosis of a subsequent disabling course in a population-based cohort of patients with pediatric-onset CD. METHODS: Among 537 patients with pediatric CD diagnosed at <17 years of age, 309 (57%) with 5-year follow-up were included. Clinical and demographic factors associated with subsequent disabling CD were studied. Three definitions of disabling CD were used: Saint-Antoine and Liège Hospitals' definitions and a new pediatric definition based on the presence at maximal follow-up of: 1) growth delay defined by body mass index (BMI), weight or height lower than -2 SD Z score; and 2) at least one intestinal resection or two anal interventions. Predictors were determined using multivariate analyses and their accuracy using the kappa method considering a relevant value ≥0.6. RESULTS: According to the Saint-Antoine definition, the rate of disabling CD was 77% and predictors were complicated behavior and L1 location. According to the Liège definition, the rate was 37% and predictors included behavior, upper gastrointestinal disease, and extraintestinal manifestations. According to the pediatric definition, the rate of disabling CD was 15%, and predictors included complicated behavior, age <14, and growth delay at diagnosis. Kappa values for each combination of predictors were, respectively, 0.2, 0.3, and 0.2 and were nonrelevant. CONCLUSIONS: Clinical parameters at diagnosis are insufficient to predict a disabling course of pediatric CD. More complex models including serological and genetic biomarkers should be tested. (Inflamm Bowel Dis 2012;).

• Ulcerative colitis as a progressive disease: The forgotten evidence.

  Authors: Joana Torres, Vincent Billioud, David B Sachar, Laurent Peyrin-Biroulet, Jean-Frédéric Colombel

  Inflammatory bowel diseases. 12/2011;

  In the management of Crohn's disease, earlier aggressive treatment is becoming accepted as a strategy to prevent or retard progression to irreversible bowel damage. It is not yet clear, however, ifIn the management of Crohn's disease, earlier aggressive treatment is becoming accepted as a strategy to prevent or retard progression to irreversible bowel damage. It is not yet clear, however, if this same concept should be applied to ulcerative colitis. Hence, we review herein the long-term structural and functional consequences of this latter disease. Disease progression in ulcerative colitis takes six principal forms: proximal extension, stricturing, pseudopolyposis, dysmotility, anorectal dysfunction, and impaired permeability. The precise incidence of these complications and the ability of earlier, more aggressive treatment to prevent them have yet to be determined. (Inflamm Bowel Dis 2011;).

• Safety and efficacy of extractible self-expandable metal stents in the treatment of Crohn's disease intestinal strictures: A prospective pilot study.

  Authors: Alain Attar, Vincent Maunoury, Kouroche Vahedi, Gwennola Vernier-Massouille, Setakhr Vida, Philippe Bulois, Jean Frédéric Colombel, Yoram Bouhnik

  Inflammatory bowel diseases. 12/2011;

  BACKGROUND: Endoscopic management of Crohn's disease (CD) intestinal strictures with balloon dilation is effective; however, recurrences are frequent and require further dilations or surgery. The useBACKGROUND: Endoscopic management of Crohn's disease (CD) intestinal strictures with balloon dilation is effective; however, recurrences are frequent and require further dilations or surgery. The use of extractible metallic stents may be as effective as balloon dilation with fewer recurrences. The aim was to investigate in a prospective pilot study the feasibility and clinical effectiveness of the use of extractible stents in the treatment of CD intestinal strictures. METHODS: In two tertiary referral centers, quiescent CD patients except for obstructive symptoms associated with intestinal stenosis of less than 50 mm length on enterography were eligible for transitory stent placement, initially planned to be retrieved after 8 weeks, which was secondarily reduced to 4 weeks after patient 3. RESULTS: Eleven patients (six males, five females, median age 34 years [range 18-66]) were prospectively included. The sites of intestinal stenosis were an ileocolonic anastomosis, an ileosigmoidic anastomosis, and the surgically untreated terminal ileum in eight, one, and two patients, respectively. Stent placement was technically successful in 10 patients. Obstructive symptoms were relieved in 6 out of 10 patients. Two patients needed surgery related to the procedure. Six downstream migrations were observed. Only one patient could have the stent extracted as scheduled on day 28 and remains symptom-free after 73 months of follow-up. CONCLUSIONS: Even if stenting appears an effective technique in treating symptomatic CD intestinal strictures, the procedure is associated with a prohibitively high rate of spontaneous migrations and complications. (Inflamm Bowel Dis 2011;).

• Identification of areas of functioning and disability addressed in inflammatory bowel disease-specific patient reported outcome measures.

  Authors: Ulrike Achleitner, Michaela Coenen, Jean-Frédéric Colombel, Laurent Peyrin-Biroulet, Narine Sahakyan, Alarcos Cieza

  Journal of Crohn's & colitis. 12/2011;

  BACKGROUND AND AIMS: Patient-reported outcome measures (PROMs) make it possible to assess health-status problems from the perspective of persons suffering from a disease. The objective of the paperBACKGROUND AND AIMS: Patient-reported outcome measures (PROMs) make it possible to assess health-status problems from the perspective of persons suffering from a disease. The objective of the paper is to examine and compare the contents of PROMs related to IBD based on the World Health Organization's International Classification of Functioning, Disability and Health (ICF) as the frame of reference. METHODS: A systematic literature review (1999-2009) in the databases Medline, EMBASE, PsycINFO, CINAHL and CENTRAL was performed to select IBD-specific PROMs. Abstracts and full-text articles were checked applying predefined eligibility criteria; IBD-specific PROMs were identified. The contents of the identified PROMs were examined by linking the items to ICF categories. The linked ICF categories of the PROMs were then compared. RESULTS: The review resulted in the selection of eight IBD-specific PROMs (e.g., Cleveland Global Quality of Life, Inflammatory Bowel Disease Quality of Life Questionnaire, Inflammatory Bowel Disease Questionnaire-32, Rating Form of IBD Patient Concerns, Short Inflammatory Bowel Disease Questionnaire). In total, 129 items were identified, the majority of which (n=90; 69.8%) could be linked to specific ICF categories. None of the linked categories were contained in all PROMs. The most frequently identified categories were 'b1300 Energy level', 'b5254 Flatulence', 'd910 Community life' and 'd920 Recreation and leisure'. CONCLUSION: The present study provides an overview of IBD-specific PROMs and their items. The results of the content comparison provide valuable information to facilitate and account for the selection of appropriate PROMs for different purposes of data collection in clinical and research settings.

• Stevens-Johnson syndrome with sulfasalazine treatment: report of two cases.

  Authors: Lydjie Tremblay, Guillaume Pineton de Chambrun, Bénédicte De Vroey, Céline Lavogiez, Emmanuel Delaporte, Jean-Frédéric Colombel, Antoine Cortot

  Journal of Crohn's & colitis. 10/2011; 5(5):457-60.

  We report two cases of Stevens-Johnson syndrome (SJS) associated with the use of sulfasalazine in two ulcerative colitis patients previously tolerant to mesalamine. SJS and toxic epidermal necrolysisWe report two cases of Stevens-Johnson syndrome (SJS) associated with the use of sulfasalazine in two ulcerative colitis patients previously tolerant to mesalamine. SJS and toxic epidermal necrolysis (TEN) are very rare adverse cutaneous reactions that can be associated with the use of sulfasalazine. The most severe cases can result in death, and for the others, permanent skin, mucosal or ocular sequelae, which can impair the quality of life in our young IBD patients. Clinicians and patients need to be aware of the signs and symptoms that often precede the appearance of the mucocutaneous lesions in a SJS or TEN, such as fever, influenza-like symptoms, sore throat or burning eyes. For patients with SJS or TEN, immediate withdrawal of the offending medication should be done when blisters or erosions appear in the course of a drug eruption, as this may improve the prognosis.

• Mesenteric fat as a source of C reactive protein and as a target for bacterial translocation in Crohn's disease.

  Authors: Laurent Peyrin-Biroulet, Florent Gonzalez, Laurent Dubuquoy, Christel Rousseaux, Caroline Dubuquoy, Cécilia Decourcelle, Alain Saudemont, Mickael Tachon, Elodie Béclin, Marie-Françoise Odou, Christel Neut, Jean-Frédéric Colombel, Pierre Desreumaux

  Gut. 09/2011; 61(1):78-85.

  Objective: Mesenteric fat hyperplasia is a hallmark of Crohn's disease (CD), and C reactive protein (CRP) is correlated with disease activity. The authors investigated whether mesenteric adipocytesObjective: Mesenteric fat hyperplasia is a hallmark of Crohn's disease (CD), and C reactive protein (CRP) is correlated with disease activity. The authors investigated whether mesenteric adipocytes may be a source of CRP in CD and whether inflammatory and bacterial triggers may stimulate its production by adipocytes. CRP expression in the mesenteric and subcutaneous fats of patients with CD and the correlation between CRP plasma concentrations and mesenteric messenger RNA (mRNA) levels were assessed. The impact of inflammatory and bacterial challenges on CRP synthesis was tested using an adipocyte cell line. Bacterial translocation to mesenteric fat was studied in experimental models of colitis and ileitis and in patients with CD. CRP expression was increased in the mesenteric fat of patients with CD, with mRNA levels being 80 ± 40 (p<0.05) and 140 ± 65 (p=0.04) times higher than in the mesenteric fat of patients with ulcerative colitis and in the subcutaneous fat of the same CD subjects, respectively, and correlated with plasma levels. Escherichia coli (1230 ± 175-fold, p<0.01), lipopolysaccharide (26 ± 0.5-fold, p<0.01), tumour necrosis factor α (15 ± 0.3-fold, p<0.01) and interleukin-6 (10 ± 0.7-fold, p<0.05) increased CRP mRNA levels in adipocyte 3T3-L1 cells. Bacterial translocation to mesenteric fat occurred in 13% and 27% of healthy and CD subjects, respectively, and was increased in experimental colitis and ileitis. Human mesenteric adipocytes constitutively expressed mRNA for TLR2, TLR4, NOD1 and NOD2. Mesenteric fat is an important source of CRP in CD. CRP production by mesenteric adipocytes may be triggered by local inflammation and bacterial translocation to mesenteric fat, providing a mechanism whereby mesenteric fat hyperplasia may contribute to inflammatory response in CD.

• Maintenance of remission among patients with Crohn's disease on antimetabolite therapy after infliximab therapy is stopped.

  Authors: Edouard Louis, Jean-Yves Mary, Gwenola Vernier-Massouille, Jean-Charles Grimaud, Yoram Bouhnik, David Laharie, Jean-Louis Dupas, Hélène Pillant, Laurence Picon, Michel Veyrac, Mathurin Flamant, Guillaume Savoye, Raymond Jian, Martine Devos, Raphaël Porcher, Gilles Paintaud, Eric Piver, Jean-Frédéric Colombel, Marc Lemann

  Gastroenterology. 09/2011; 142(1):63-70.e5; quiz e31.

  It is important to determine whether infliximab therapy can be safely interrupted in patients with Crohn's disease who have undergone a period of prolonged remission. We assessed the risk of relapseIt is important to determine whether infliximab therapy can be safely interrupted in patients with Crohn's disease who have undergone a period of prolonged remission. We assessed the risk of relapse after infliximab therapy was discontinued in patients on combined maintenance therapy with antimetabolites and identified factors associated with relapse. We performed a prospective study of 115 patients with Crohn's disease who were treated for at least 1 year with scheduled infliximab and an antimetabolite and had been in corticosteroid-free remission for at least 6 months. Infliximab was stopped, and patients were followed up for at least 1 year. We associated demographic, clinical, and biologic factors with time to relapse using a Cox model. After a median follow-up period of 28 months, 52 of the 115 patients experienced a relapse; the 1-year relapse rate was 43.9% ± 5.0%. Based on multivariable analysis, risk factors for relapse included male sex, the absence of surgical resection, leukocyte counts >6.0 × 10(9)/L, and levels of hemoglobin ≤145 g/L, C-reactive protein ≥5.0 mg/L, and fecal calprotectin ≥300 μg/g. Patients with no more than 2 of these risk factors (approximately 29% of the study population) had a 15% risk of relapse within 1 year. Re-treatment with infliximab was effective and well tolerated in 88% of patients who experienced a relapse. Approximately 50% of patients with Crohn's disease who were treated for at least 1 year with infliximab and an antimetabolite agent experienced a relapse within 1 year after discontinuation of infliximab. However, patients with a low risk of relapse can be identified using a combination of clinical and biologic markers.

• Successful treatment with adalimumab in a familial case of gastrointestinal Behcet's disease.

  Authors: Chiara De Cassan, Bénédicte De Vroey, Catherine Dussault, Eric Hachulla, Sebastien Buche, Jean-Frédéric Colombel

  Journal of Crohn's & colitis. 09/2011; 5(4):364-8.

  We present here two siblings with a history of recurrent oral and genital ulcers, neurological and gastrointestinal manifestations. The diagnosis of Behçet's disease in a context of familialWe present here two siblings with a history of recurrent oral and genital ulcers, neurological and gastrointestinal manifestations. The diagnosis of Behçet's disease in a context of familial aggregation was assumed. Facing repeated steroid-dependent flares and failure of maintenance therapies with colchicine and intolerance to pentoxifilline and disulone, adalimumab was started. Rapid response was observed in both patients, with clinical remission after induction therapy, which currently sustains under maintenance schedule. This case report suggests the effectiveness of adalimumab as first anti-TNFα in case of steroid-dependent/resistant gastrointestinal BD.