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See detailAdalimumab dose escalation and dose de-escalation success rate and predictors in a large national cohort of Crohn's patients.
Baert, Filip; Glorieus, Elien; Reenaers, Catherine et al

in Journal of Crohn’s and Colitis (2013), 7(2),

BACKGROUND AND AIMS: Adalimumab is efficacious in inducing and maintaining remission in Crohn's disease but dose escalation is needed in 30-40% after 1year. Attempts for dose de-escalation have not been ... [more ▼]

BACKGROUND AND AIMS: Adalimumab is efficacious in inducing and maintaining remission in Crohn's disease but dose escalation is needed in 30-40% after 1year. Attempts for dose de-escalation have not been studied. This study aimed to assess the need for, predictors, and outcome of dose escalation and de-escalation in a large cohort of adalimumab treated Crohn's patients. METHODS: All consecutive patients treated with open label adalimumab for active Crohn's disease from the participating centres were included in this cohort study. A detailed retrospective chart review was performed to look for possible factors predicting outcome. RESULTS: Eighty four percent of 720 patients had a primary response and were followed up for a median of 14months. Thirty four percent needed escalation after a median of 7months (0-55months). Multivariate predictors for dose escalation were the following: prior anti-TNF use (p<0.0001), no concomitant azathioprine or <3m (p<0.02) and abnormal CRP at start (p<0.05). Dose escalation re-induced response for at least 6months in 67%. Only abnormal CRP at start correlated with failure of dose escalation (p=0.02). Dose de-escalation was attempted in 54% and was successful in 63%. After a median follow-up of 14m adalimumab was discontinued in 29% of patients. CONCLUSION: In this study real life nationwide cohort of Crohn's patients treated with adalimumab dose escalation was needed in 34% and was successful in 67%. Dose de-escalation was attempted in 54% and was successful in 63%. Overall 71% of patients maintained long term response on adalimumab. [less ▲]

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See detailCommentary: predicting complicated Crohn's disease and surgery--phenotypes, genetics, serology and psychological characteristics of a population-based cohort.
Benitez, Jose Manuel; LOUIS, Edouard ULg

in Alimentary pharmacology & therapeutics (2013), 38(5), 555-6

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See detailVedolizumab as induction and maintenance therapy for Crohn's disease.
Sandborn, William J.; Feagan, Brian G.; Rutgeerts, Paul et al

in The New England journal of medicine (2013), 369(8), 711-21

BACKGROUND: The efficacy of vedolizumab, an alpha4beta7 integrin antibody, in Crohn's disease is unknown. METHODS: In an integrated study with separate induction and maintenance trials, we assessed ... [more ▼]

BACKGROUND: The efficacy of vedolizumab, an alpha4beta7 integrin antibody, in Crohn's disease is unknown. METHODS: In an integrated study with separate induction and maintenance trials, we assessed intravenous vedolizumab therapy (300 mg) in adults with active Crohn's disease. In the induction trial, 368 patients were randomly assigned to receive vedolizumab or placebo at weeks 0 and 2 (cohort 1), and 747 patients received open-label vedolizumab at weeks 0 and 2 (cohort 2); disease status was assessed at week 6. In the maintenance trial, 461 patients who had had a response to vedolizumab were randomly assigned to receive placebo or vedolizumab every 8 or 4 weeks until week 52. RESULTS: At week 6, a total of 14.5% of the patients in cohort 1 who received vedolizumab and 6.8% who received placebo were in clinical remission (i.e., had a score on the Crohn's Disease Activity Index [CDAI] of </=150, with scores ranging from 0 to approximately 600 and higher scores indicating greater disease activity) (P=0.02); a total of 31.4% and 25.7% of the patients, respectively, had a CDAI-100 response (>/=100-point decrease in the CDAI score) (P=0.23). Among patients in cohorts 1 and 2 who had a response to induction therapy, 39.0% and 36.4% of those assigned to vedolizumab every 8 weeks and every 4 weeks, respectively, were in clinical remission at week 52, as compared with 21.6% assigned to placebo (P<0.001 and P=0.004 for the two vedolizumab groups, respectively, vs. placebo). Antibodies against vedolizumab developed in 4.0% of the patients. Nasopharyngitis occurred more frequently, and headache and abdominal pain less frequently, in patients receiving vedolizumab than in patients receiving placebo. Vedolizumab, as compared with placebo, was associated with a higher rate of serious adverse events (24.4% vs. 15.3%), infections (44.1% vs. 40.2%), and serious infections (5.5% vs. 3.0%). CONCLUSIONS: Vedolizumab-treated patients with active Crohn's disease were more likely than patients receiving placebo to have a remission, but not a CDAI-100 response, at week 6; patients with a response to induction therapy who continued to receive vedolizumab (rather than switching to placebo) were more likely to be in remission at week 52. Adverse events were more common with vedolizumab. (Funded by Millennium Pharmaceuticals; GEMINI 2 ClinicalTrials.gov number, NCT00783692.). [less ▲]

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See detailFDG PET/CT in Crohn's disease: correlation of quantitative FDG PET/CT parameters with clinical and endoscopic surrogate markers of disease activity.
Saboury, Babak; Salavati, Ali; Brothers, Alex et al

in European journal of nuclear medicine and molecular imaging (2013)

PURPOSE: The aim of this study was to determine the feasibility and potential clinical utility of assessment of Crohn's disease (CD) activity by 18F-fluorodeoxyglucose (FDG) positron emission tomography ... [more ▼]

PURPOSE: The aim of this study was to determine the feasibility and potential clinical utility of assessment of Crohn's disease (CD) activity by 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT employing a new quantitative approach. METHODS: A total of 22 subjects (mean age 37) with CD who had undergone FDG PET/CT followed by ileocolonoscopy within 1 week were included in this analysis. The CD endoscopy index of severity (CDEIS) for various bowel segments was calculated. The CD activity index (CDAI) was evaluated, and fecal calprotectin was measured. On PET, regions with increased FDG uptake in large bowel were segmented with an adaptive contrast-oriented thresholding algorithm, and metabolically active volume (MAV), uncorrected mean standardized uptake value (SUVmean), partial volume-corrected SUVmean (PVC-SUVmean), SUVmax, uncorrected total lesion glycolysis (TLG = MAV x SUVmean), and PVC total lesion glycolysis (PVC-TLG = MAV x PVC-SUVmean) were measured. Global CD activity score (GCDAS) was calculated as the sum of PVC-TLG over all clinically significant FDG-avid regions in each subject. Correlations between regional PET quantification measures (SUVs, TLGs) and CDEIS were calculated. Correlations between the global PET quantification measure (GCDAS, global SUVs) with CDAI, fecal calprotectin, CDEIS, and CRP level were also calculated. RESULTS: SUVmax, PVC-SUVmean, and PVC-TLG significantly correlated with segment CDEIS subscores (r = 0.50, r = 0.69, and r = 0.31, respectively; p < 0.05). GCDAS significantly correlated with CDAI and fecal calprotectin (r = 0.64 and r = 0.51, respectively; p < 0.05). CONCLUSION: By employing this new quantitative approach, we were able to calculate indices of regional and global CD activity, which correlated well with both clinical and pathological disease activity surrogate markers. This approach may be of clinical importance in measuring both global disease activity and treatment response in patients with CD. [less ▲]

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See detailMaladie de Crohn et entero-IRM evaluation de l'activite de la maladie et du dommage tissulaire.
Cousin, F.; Louis, Edouard ULg; Meunier, P.

in Revue medicale suisse (2013), 9(395), 1502-6

Crohn's disease is an inflammatory bowel disease that affects mainly young people and includes periods of remission interspersed with occasional flare-ups. Entero-MR (Magnetic Resonance) is a non ... [more ▼]

Crohn's disease is an inflammatory bowel disease that affects mainly young people and includes periods of remission interspersed with occasional flare-ups. Entero-MR (Magnetic Resonance) is a non-radiating and a non-invasive tomography imaging technique. Entero-MR has recently proven its ability to assess inflammatory activity and structural damage of the bowel in Crohn's disease which are fundamental elements in the therapy planning. These considerations explain why entero-MR is playing an increasing role in the evaluation of Crohn's disease. [less ▲]

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See detailSerum adalimumab concentration and clinical remission in patients with Crohn's disease.
Chiu, Yi-Lin; Rubin, David T.; Vermeire, Severine et al

in Inflammatory bowel diseases (2013), 19(6), 1112-22

BACKGROUND: Drug concentration monitoring may be useful to guide therapeutic adjustments for anti-tumor necrosis factor agents in Crohn's disease. The relationship between serum adalimumab concentrations ... [more ▼]

BACKGROUND: Drug concentration monitoring may be useful to guide therapeutic adjustments for anti-tumor necrosis factor agents in Crohn's disease. The relationship between serum adalimumab concentrations and clinical outcomes was assessed using data from CLinical Assessment of Adalimumab Safety and Efficacy Studied as Induction Therapy in Crohn's Disease (CLASSIC) I/II. METHODS: Serum adalimumab concentrations at week 4 of CLASSIC I and weeks 4, 24, and 56 of CLASSIC II were compared by clinical remission status (yes/no). Logistic regression and Classification and Regression Tree analyses explored factors associated with remission at weeks 4, 24, and 56. Threshold analyses and receiver operating characteristic curves evaluated the relationship between serum concentrations and clinical remission/response. RESULTS: Serum adalimumab concentrations for 275 patients were available. Median adalimumab concentrations were significantly higher in patients who achieved clinical remission than those who did not at week 4 of CLASSIC I (8.10 versus 5.05 microg/mL, P < 0.05). At all time points, adalimumab concentrations demonstrated considerable variability and overlap between patients with and without remission. With Classification and Regression Tree analyses, baseline Crohn's Disease Activity Index, baseline C-reactive protein, and adalimumab concentrations were associated with early remission at week 4 of CLASSIC I and week 4 of CLASSIC II, but not at weeks 24 and 56. Receiver operating characteristic curves demonstrated low utility of cutoff thresholds to discriminate by clinical response/remission status. CONCLUSIONS: A positive association between serum adalimumab concentration and remission was identified at several time points. A threshold concentration reliably associated with remission was not identified. Further prospective evaluations are needed before recommendations for adalimumab concentration monitoring can be made. [less ▲]

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See detailRole of endoscopy, cross-sectional imaging and biomarkers in Crohn's disease monitoring.
Benitez, Jose-Manuel; Meuwis, Marie-Alice ULg; Reenaers, Catherine et al

in Gut (2013), 62(12), 1806-16

Crohn's disease is characterised by recurrent and/or chronic inflammation of the gastrointestinal tract leading to cumulative intestinal tissue damage. Treatment tailoring to try to prevent this tissue ... [more ▼]

Crohn's disease is characterised by recurrent and/or chronic inflammation of the gastrointestinal tract leading to cumulative intestinal tissue damage. Treatment tailoring to try to prevent this tissue damage as well as achieve optimal benefit/risk ratio over the whole disease course is becoming an important aspect of Crohn's disease management. For decades, clinical symptoms have been the main trigger for diagnostic procedures and treatment strategy adaptations. However, the correlation between symptoms and intestinal lesions is only weak. Furthermore, preliminary evidence suggests that a state of remission beyond the simple control of clinical symptoms, and including mucosal healing, may be associated with better disease outcome. Therefore monitoring the disease through the use of endoscopy and cross-sectional imaging is proposed. However, the degree of mucosal or bowel wall healing that needs to be reached to improve disease outcome has not been appropriately studied. Furthermore, owing to their invasive nature and cost, endoscopy and cross-sectional imaging are not optimal tools for the patients or the payers. The use of biomarkers as surrogate markers of intestinal and systemic inflammation might help. Two biomarkers have been most broadly assessed in Crohn's disease: C-reactive protein and faecal calprotectin. These markers correlate significantly with endoscopic lesions, with the risk of relapse and with response to therapy. They could be used to help make decisions about diagnostic procedures and treatment. In particular, with the use of appropriate threshold values, they could determine the need for endoscopic or medical imaging procedures to confirm the disease activity state. [less ▲]

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See detailStrategic use of immunosuppressants and anti-TNF in inflammatory bowel disease.
Louis, Edouard ULg

in Digestive diseases (Basel, Switzerland) (2013), 31(2), 207-12

Controlled trials and meta-analyses have shown that immunosuppressants are effective in steroid-dependent Crohn's disease (CD) and, although less well demonstrated, ulcerative colitis (UC). It has also ... [more ▼]

Controlled trials and meta-analyses have shown that immunosuppressants are effective in steroid-dependent Crohn's disease (CD) and, although less well demonstrated, ulcerative colitis (UC). It has also been demonstrated that anti-TNF are effective in steroid-dependent and steroid-refractory CD and UC. Anti-TNF can also decrease hospitalization rate and the need for surgery. This seems also to be the case for immunosuppressants. The early use of anti-TNF seems more effective than later use, and early mucosal healing is associated with decreased rate of surgery. On the contrary, early use of purine analogues does not seem to improve outcome in CD. Anti-TNF therapies have been shown superior to immunosuppressants and combination therapy superior to anti-TNF monotherapy in inducing steroid-free remission and mucosal healing. The main strategic questions which remain at this stage include: When to start immunosuppressants or anti-TNF? Is there still a place for immunosuppressant monotherapy? How to optimize anti-TNF? Is it possible to stop anti-TNF? The main justification of immunosuppressant monotherapy is the low cost of this treatment and the possibility of achieving a very stable and long-standing remission in a subset of patients. According to this and provided there is no rapid need for more effective therapy, this treatment could be tried in any inflammatory bowel disease patient not correctly maintained after a course of steroids and 5-aminosalicylic acid. However, the failure to respond to this treatment should be recognized early and a step up to anti-TNF considered. An anti-TNF treatment should be considered early in patients at risk of rapid evolution towards tissue damage and complications. The benefit/risk of the immunosuppressant + anti-TNF combination therapy should be assessed on a case-by-case basis. Anti-TNF treatment should always be fully optimized by adapting dosage and potentially adding an immunosuppressant before considering treatment failure. Treatment de-escalation should only be considered when a long-standing stable remission has been achieved both clinically and biologically. The cost sparing and theoretical decrease in complication risk should be put in perspective with the risk of relapse and disease progression. [less ▲]

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See detailConsecutive fecal calprotectin measurements to predict relapse in patients with ulcerative colitis receiving infliximab maintenance therapy.
De Vos, Martine; Louis, Edouard ULg; Jahnsen, Jorgen et al

in Inflammatory bowel diseases (2013), 19(10), 2111-7

BACKGROUND: This study examined whether fecal calprotectin can be used in daily practice as a marker to monitor patients with ulcerative colitis (UC) receiving infliximab maintenance therapy. METHODS ... [more ▼]

BACKGROUND: This study examined whether fecal calprotectin can be used in daily practice as a marker to monitor patients with ulcerative colitis (UC) receiving infliximab maintenance therapy. METHODS: This prospective multicenter study enrolled adult patients with UC in clinical remission under infliximab maintenance therapy. Fecal calprotectin levels were measured every 4 weeks. Sigmoidoscopies were performed at inclusion and at study end. Relapse was defined as a clinical need for change in treatment or an endoscopic Mayo subscore of >/=2 at week 52. Sustained deep remission was defined as a partial Mayo score <3 at all points and an endoscopic Mayo score 0 at week 52. RESULTS: Full analysis was possible for 87 of 113 included patients with UC (77%). Of these patients, 30 (34.4%) were considered to be in sustained deep remission and 13 (14.9%) to have relapsed. Calprotectin levels in patients with sustained deep remission remained very low (median < 40 mg/kg at all time points). Patients who flared had significantly higher calprotectin levels (median > 300 mg/kg) already 3 months before the flare. Further receiver operator curve analysis suggested that a calprotectin level >300 mg/kg had a reasonable sensitivity (58.3%) and specificity (93.3%) to model flare. Two consecutive calprotectin measurements of >300 mg/kg with 1-month interval were identified as the best predictor of flare (61.5% sensitivity and 100% specificity). CONCLUSIONS: Fecal calprotectin can be used in daily practice to monitor patients with UC receiving infliximab maintenance therapy. Two consecutive measurements >300 mg/kg is more specific than a single measurement for predicting relapse. [less ▲]

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See detailSerum calprotectin as a biomarker for Crohn's disease.
Meuwis, Marie-Alice ULg; Vernier-Massouille, G.; Grimaud, J. C. et al

in Journal of Crohn's & colitis (2013), 7(12), 678-83

BACKGROUND AND AIMS: In Crohn's disease, correlation between clinical assessment and disease activity at tissue level is weak. Our aim was to evaluate the value of serum calprotectin as a biomarker for ... [more ▼]

BACKGROUND AND AIMS: In Crohn's disease, correlation between clinical assessment and disease activity at tissue level is weak. Our aim was to evaluate the value of serum calprotectin as a biomarker for Crohn's disease. METHODS: The STORI trial patients (n=115) were studied at baseline, in clinical remission before infliximab withdrawal, or at the time of relapse after infliximab withdrawal. Forty healthy controls were also studied. Serum calprotectin level was measured by ELISA. Data were analyzed through correlation analyses, Kaplan Meier curves and Cox model, using available Crohn's Disease Activity Index (CDAI), Crohn's Disease Endoscopic Index of Severity (CDEIS), fecal calprotectin and C-reactive protein levels (hsCRP). RESULTS: Median serum calprotectin was 8892 ng/mL (range: 410-125,000 ng/mL) in Crohn disease patients as compared with 1318 ng/mL (range: 215.8-3770 ng/mL) in controls (P<0.0001). Serum calprotectin was significantly higher for active disease (median=19,584 ng/mL) than for inactive disease (median=8353 ng/mL) (P<0.0001). Serum calprotectin correlated with hsCRP (r=0.4092, P<0.0001) and CDAI (r=0.4442, P<0.0001), but not with CDEIS, on the contrary to fecal calprotectin (r=0.6458, 0.5515, 0.2577 with P<0.0001, P<0.0001, P=0.019 respectively). In multivariate analysis, serum calprotectin used as a discrete variable (threshold: 5675 ng/ml), appeared complementary to hsCRP (>5 mg/l) and fecal calprotectin (>250 mug/g) to predict relapse after infliximab withdrawal (P=0.0173, 0.0024 and 0.0002; HR: 3.191, 3.561 and 4.120). CONCLUSIONS: As a CD biomarker, serum calprotectin has a similar profile as hsCRP. It is also complementary to fecal calprotectin and hsCRP for prediction of relapse after infliximab withdrawal. [less ▲]

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See detailEvolving definitions of remission in Crohn's disease.
Panaccione, Remo; Colombel, Jean-Frederic; Louis, Edouard ULg et al

in Inflammatory bowel diseases (2013), 19(8), 1645-53

BACKGROUND: Using clinical symptoms alone to inform treatment decisions in Crohn's disease (CD) may increase the risk of disease progression and complications. Treatment beyond symptoms may offer improved ... [more ▼]

BACKGROUND: Using clinical symptoms alone to inform treatment decisions in Crohn's disease (CD) may increase the risk of disease progression and complications. Treatment beyond symptoms may offer improved outcomes. METHODS: We explore alternative definitions of remission, beyond traditional clinical remission, incorporating more objective parameters of inflammation control, which may support prevention or delay the disease progression. These definitions could serve as a platform for future clinical research, evaluating whether treating beyond symptoms alters the natural history of CD. RESULTS: Proposed definitions may include endoscopic remission (mucosal healing), normalization of serologic or fecal markers of inflammation, and even radiographic remission, in addition to clinical remission (symptom control). Endoscopic remission is the leading candidate for inclusion because it is the best studied. The definition should include considerations for both early and late disease given that in late disease, which may be associated with operation-related symptoms or irreversible bowel damage, symptomatic remission may not achievable. Desired outcomes in early disease are complete absence of symptoms, no disease progression, no complications or disability, and normal quality of life. In late disease, there are stabilization of noninflammatory symptoms, no progression of damage or disability, and improved quality of life. CONCLUSIONS: Over time, we anticipate that a working definition of remission that includes both biological remission and clinical remission will evolve and be evaluated in clinical trials. Our proposed definition is a possible starting point for that evolution. Ultimately, the goal in evolving the definition of remission is to improve the outcomes in patients with CD. [less ▲]

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See detailOptimising monitoring in the management of Crohn's disease: a physician's perspective.
Papay, Pavol; Ignjatovic, Ana; Karmiris, Konstantinos et al

in Journal of Crohn's & colitis (2013), 7(8), 653-69

Management of Crohn's disease has traditionally placed high value on subjective symptom assessment; however, it is increasingly appreciated that patient symptoms and objective parameters of inflammation ... [more ▼]

Management of Crohn's disease has traditionally placed high value on subjective symptom assessment; however, it is increasingly appreciated that patient symptoms and objective parameters of inflammation can be disconnected. Therefore, strategies that objectively monitor inflammatory activity should be utilised throughout the disease course to optimise patient management. Initially, a thorough assessment of the severity, location and extent of disease is needed to ensure a correct diagnosis, identify any complications, help assess prognosis and select appropriate therapy. During follow-up, clinical decision-making should be driven by disease activity monitoring, with the aim of optimising treatment for tight disease control. However, few data exist to guide the choice of monitoring tools and the frequency of their use. Furthermore, adaption of monitoring strategies for symptomatic, asymptomatic and post-operative patients has not been well defined. The Annual excHangE on the ADvances in Inflammatory Bowel Disease (IBD Ahead) 2011 educational programme, which included approximately 600 gastroenterologists from 36 countries, has developed practice recommendations for the optimal monitoring of Crohn's disease based on evidence and/or expert opinion. These recommendations address the need to incorporate different modalities of disease assessment (symptom and endoscopic assessment, measurement of biomarkers of inflammatory activity and cross-sectional imaging) into robust monitoring. Furthermore, the importance of measuring and recording parameters in a standardised fashion to enable longitudinal evaluation of disease activity is highlighted. [less ▲]

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See detailLetter: should immunosuppressive therapy be started with adalimumab in Crohn's disease? Authors' reply.
Reenaers, C.; Louis, Edouard ULg; Belaiche, Jacques ULg et al

in Alimentary pharmacology & therapeutics (2013), 37(7), 752-3

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See detailEffects of infliximab therapy on transmural lesions as assessed by magnetic resonance enteroclysis in patients with ileal Crohn's disease.
Van Assche, Gert; Herrmann, Karin A.; Louis, Edouard ULg et al

in Journal of Crohn's & colitis (2013), 7(12), 950-7

BACKGROUND AND AIMS: Anti TNF therapy induces mucosal healing in patients with Crohn's disease, but the effects on transmural inflammation in the ileum are not well understood. Magnetic resonance ... [more ▼]

BACKGROUND AND AIMS: Anti TNF therapy induces mucosal healing in patients with Crohn's disease, but the effects on transmural inflammation in the ileum are not well understood. Magnetic resonance-enteroclysis (MRE) offers excellent imaging of transmural and peri-enteric lesions in Crohn's ileitis and we aimed to study its responsiveness to anti TNF therapy. METHODS: In this multi-center prospective trial, anti TNF naive patients with ileal Crohn's disease and with increased CRP and contrast enhanced wall thickening received infliximab 5 mg/kg at weeks 0, 2 and 6, and q8 weeks maintenance MRE was performed at baseline, 2 weeks and 6 months and assessed based on a predefined MRE score of severity in ileal Crohn's Disease. RESULTS: Twenty patients were included; of those, 18 patients underwent MRE at week 2 and 15 patients at weeks 2 and 26 as scheduled. Inflammatory components of the MRE index decreased by >/=2 points and by >/=50% at week 26 (primary endpoint) in 40% and 32% of patients (per protocol and intention to treat analysis, respectively). The MRE index improved in 44% at week 2 and in 80% at week 26. Complete absence of inflammatory lesions was observed in 0/18 at week 2 and 13% (2/15) at week 26. The obstructive elements did not change. Clinical and CRP improvement occurred as early as wk 2, but only CDAI correlated with the MRE index. CONCLUSION: Improvement of MRE occurs from 2 weeks after infliximab therapy onwards and correlates with clinical response but normalization of MRE is rare. [less ▲]

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See detailVedolizumab as induction and maintenance therapy for ulcerative colitis.
Feagan, Brian G.; Rutgeerts, Paul; Sands, Bruce E. et al

in The New England journal of medicine (2013), 369(8), 699-710

BACKGROUND: Gut-selective blockade of lymphocyte trafficking by vedolizumab may constitute effective treatment for ulcerative colitis. METHODS: We conducted two integrated randomized, double-blind ... [more ▼]

BACKGROUND: Gut-selective blockade of lymphocyte trafficking by vedolizumab may constitute effective treatment for ulcerative colitis. METHODS: We conducted two integrated randomized, double-blind, placebo-controlled trials of vedolizumab in patients with active disease. In the trial of induction therapy, 374 patients (cohort 1) received vedolizumab (at a dose of 300 mg) or placebo intravenously at weeks 0 and 2, and 521 patients (cohort 2) received open-label vedolizumab at weeks 0 and 2, with disease evaluation at week 6. In the trial of maintenance therapy, patients in either cohort who had a response to vedolizumab at week 6 were randomly assigned to continue receiving vedolizumab every 8 or 4 weeks or to switch to placebo for up to 52 weeks. A response was defined as a reduction in the Mayo Clinic score (range, 0 to 12, with higher scores indicating more active disease) of at least 3 points and a decrease of at least 30% from baseline, with an accompanying decrease in the rectal bleeding subscore of at least 1 point or an absolute rectal bleeding subscore of 0 or 1. RESULTS: Response rates at week 6 were 47.1% and 25.5% among patients in the vedolizumab group and placebo group, respectively (difference with adjustment for stratification factors, 21.7 percentage points; 95% confidence interval [CI], 11.6 to 31.7; P<0.001). At week 52, 41.8% of patients who continued to receive vedolizumab every 8 weeks and 44.8% of patients who continued to receive vedolizumab every 4 weeks were in clinical remission (Mayo Clinic score </=2 and no subscore >1), as compared with 15.9% of patients who switched to placebo (adjusted difference, 26.1 percentage points for vedolizumab every 8 weeks vs. placebo [95% CI, 14.9 to 37.2; P<0.001] and 29.1 percentage points for vedolizumab every 4 weeks vs. placebo [95% CI, 17.9 to 40.4; P<0.001]). The frequency of adverse events was similar in the vedolizumab and placebo groups. CONCLUSIONS: Vedolizumab was more effective than placebo as induction and maintenance therapy for ulcerative colitis. (Funded by Millennium Pharmaceuticals; GEMINI 1 ClinicalTrials.gov number, NCT00783718.). [less ▲]

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See detailCancer risk in immune-mediated inflammatory diseases (IMID).
Beyaert, Rudi; Beaugerie, Laurent; Van Assche, Gert et al

in Molecular cancer (2013), 12(1), 98

Inflammation and cancer have a profound yet ambiguous relationship. Inflammation - especially chronic inflammation - has protumorigenic effects, but inflammatory cells also mediate an immune response ... [more ▼]

Inflammation and cancer have a profound yet ambiguous relationship. Inflammation - especially chronic inflammation - has protumorigenic effects, but inflammatory cells also mediate an immune response against the tumor and immunosuppression is known to increase the risk for certain tumors.This article reviews current literature on the role of inflammation in cancer and the cancer risk in immune-mediated inflammatory diseases (IMIDs). We discuss the effect on cancer risk of different drug classes used in the treatment of IMIDs treatment, including biologicals such as tumor necrosis factor (TNF) inhibitors.Overall cancer incidence and mortality risk are similar to the general population in inflammatory bowel disease (IBD), and slightly increased for rheumatoid arthritis and psoriasis, with risk profiles differing for different tumor types. Increased risk for non-melanoma skin cancer is associated with thiopurine treatment in IBD, with the combination of anti-TNF and methotrexate in rheumatoid arthritis and with PUVA, cyclosporine and anti-TNF treatment in psoriasis. Data on the safety of using biologic or immunosuppressant therapy in IMID patients with a history of cancer are scarce.This review provides clinicians with a solid background to help them in making decisions about treatment of immune-mediated diseases in patients with a tumor history.This article is related to another review article in Molecular Cancer: http://www.molecular-cancer.com/content/12/1/86. [less ▲]

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See detaille syndrome auto-immun thyrogastrique: ses effets sur les micronutriments et la tumorigénèse gastrique.
VALDES SOCIN, Hernan Gonzalo ULg; LUTTERI, Laurence ULg; CAVALIER, Etienne ULg et al

in Revue Médicale de Liège (2013)

Summary : The thyrogastric autoimmune syndrome (TAS) was described in patients in whom the serum cross-reacted both with gastric parietal cells antigens and thyroid antigens. We report two cases ... [more ▼]

Summary : The thyrogastric autoimmune syndrome (TAS) was described in patients in whom the serum cross-reacted both with gastric parietal cells antigens and thyroid antigens. We report two cases illustrating the spectrum of pathogical features of TAS. The first case associates Hashimoto’s thyroiditis and anemia perniciosa,and develops a gastric neuroendocrine tumor during follow up. The second case presents with a Graves’ disease and an autoimmune reversible gastritis, secondary to Helicobacter Pylori. Whereas type III autoimmune polyendocrinopathy is rare, TAS is frequent in our experience. Some 13% (32/240) of patients that we have prospectively followed affected with thyroiditis have also autoimmune gastritis. Helicobacter pylori is clearly implicated in 16% of autoimmune gastritis cases. Infection, malabsorption and gastritis are potentially reversible after bacterial eradication treatment. In the other 84% of gastritis patients, no histological or serological proof of Helicobacter pylori is found. Gastric autoimmunity is then irreversible, leading to gastric severe atrophy, hypochlorhydria and hypergastrinemia. Hypergastrinemia stimulates enterochromaffin cell hyperplasia, possibly progressing c to neuroendocrine tumors. We propose a diagnostic approach to improve the characterization of TAS. We review the literature on the subject and discuss some interesting animal models of infectious gastric autoimmunity [less ▲]

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See detailHost-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
Jostins, Luke; Ripke, Stephan; Weersma, Rinse K. et al

in Nature (2012), 491(7422), 119-24

Crohn's disease and ulcerative colitis, the two common forms of inflammatory bowel disease (IBD), affect over 2.5 million people of European ancestry, with rising prevalence in other populations. Genome ... [more ▼]

Crohn's disease and ulcerative colitis, the two common forms of inflammatory bowel disease (IBD), affect over 2.5 million people of European ancestry, with rising prevalence in other populations. Genome-wide association studies and subsequent meta-analyses of these two diseases as separate phenotypes have implicated previously unsuspected mechanisms, such as autophagy, in their pathogenesis and showed that some IBD loci are shared with other inflammatory diseases. Here we expand on the knowledge of relevant pathways by undertaking a meta-analysis of Crohn's disease and ulcerative colitis genome-wide association scans, followed by extensive validation of significant findings, with a combined total of more than 75,000 cases and controls. We identify 71 new associations, for a total of 163 IBD loci, that meet genome-wide significance thresholds. Most loci contribute to both phenotypes, and both directional (consistently favouring one allele over the course of human history) and balancing (favouring the retention of both alleles within populations) selection effects are evident. Many IBD loci are also implicated in other immune-mediated disorders, most notably with ankylosing spondylitis and psoriasis. We also observe considerable overlap between susceptibility loci for IBD and mycobacterial infection. Gene co-expression network analysis emphasizes this relationship, with pathways shared between host responses to mycobacteria and those predisposing to IBD. [less ▲]

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See detailQuinze ans d'anti-TNF dans la maladie de Crohn: comment tirer le meilleur de cette revolution therapeutique?
Louis, Edouard ULg; REENAERS, Catherine ULg; Meuwis, Marie-Alice ULg et al

in Revue Médicale de Liège (2012), 67 Spec No

After fifteen years of use, the anti-TNF antibodies have become the corner stone of the treatment of moderate and severe Crohn's disease. The skill acquired over the years through experimental trials and ... [more ▼]

After fifteen years of use, the anti-TNF antibodies have become the corner stone of the treatment of moderate and severe Crohn's disease. The skill acquired over the years through experimental trials and clinical experience leads to increased therapeutic efficacy and minimized risks. These antibodies are introduced increasingly earlier in Crohn's disease as well as in a broader range of patients, aiming at changing the natural history of the diseases by avoiding the development of intestinal tissue damage and complications. [less ▲]

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