Potential Proteomic Biomarkers Associated To Mucosal Healing In Crohn’s Disease
MEUWIS, Marie-Alice ; Baiwir, Dominique ; Mazzucchelli, Gabriel et al
Poster (2014, October 06)
Introduction and objectives: In Crohn's disease (CD), there is a discrepancy between clinical activity of the disease (symptoms) and intestinal healing. However absence of tissue healing is associated ... [more ▼]
Introduction and objectives: In Crohn's disease (CD), there is a discrepancy between clinical activity of the disease (symptoms) and intestinal healing. However absence of tissue healing is associated with the risk of relapse and tissue damage progression. Endoscopy is costly and invasive. Hence biomarkers correlating with intestinal healing could improve disease management. We aimed to identify potential biomarkers associated to CD mucosal healing by a shotgun proteomics label free study. Methods: We used the STORI clinical trial cohort (n=103) aiming at identifying markers associated to relapse prediction after Infliximab treatment withdrawals. We used serum samples of patients in clinical remission, grouped according to the degree of intestinal healing seen at endoscopy. We performed depletion of the 20 most abundant plasma proteins on each serum pools and ran a proteomics label free differential analysis using 2D-nanoUPLC-MSE HDMS Synapt G1 for data acquisition and Protein Lynks Global Server vs 2.4 for data analysis (Waters, Corp., Milford, USA). Results and Discussion: We obtained potential biomarkers and designed a multiplexed -selected reaction monitoring (SRM) method for validation of these candidates in each individual patient. The method may also be tested in an independent set of IBD patients with and without mucosal healing. Conclusions: This research strategy and results of SRM validation of potential biomarkers associated to mucosal healing in this cohort of CD patients as well as the tests done on other CD patients, may provide new opportunities for CD follow-up tests development. [less ▲]Detailed reference viewed: 6 (0 ULg)
Data dependent versus Data independent acquisition applied to samples with different protein dynamic range
Smargiasso, Nicolas ; Mazzucchelli, Gabriel ; Baiwir, Dominique et al
Poster (2014)Detailed reference viewed: 20 (1 ULg)
Comparison of two FFPE preparation methods using label-free shotgun proteomics: Application to tissues of diverticulitis patients.
; Bertrand, Virginie ; Longuespée, Rémi et al
in Journal of proteomics (2014), 112C
Formalin-fixed paraffin-embedded (FFPE) specimens of patients are useful sources of materials for clinical research and have recently gained interest for use in the discovery of clinical proteomic ... [more ▼]
Formalin-fixed paraffin-embedded (FFPE) specimens of patients are useful sources of materials for clinical research and have recently gained interest for use in the discovery of clinical proteomic biomarkers. However, the critical step in this field is the ability to obtain an efficient and repeatable extraction using the limited quantities of material available for research in hospital biobanks. This work describes the evaluation of the peptide/protein extraction using FFPE sections treated by the following two methods before shotgun proteomic analysis: a commercial solution (FFPE-FASP) (filter aided sample preparation) and an antigen retrieval-derived protocol (On Slice AR). Their efficiencies and repeatabilities are compared using data-independent differential quantitative label-free analysis. FFPE-FASP was shown to be globally better both qualitatively and quantitatively than On Slice AR. FFPE-FASP was tested on several samples, and differential analysis was used to compare the tissues of diverticulitis patients (healthy and inflammatory tissues). In this differential proteomic analysis using retrospective clinical FFPE material, FFPE-FASP was reproducible and provided a high number of confident protein identifications, highlighting potential protein biomarkers. BIOLOGICAL SIGNIFICANCE: In clinical proteomics, FFPE is an important resource for retrospective analysis and for the discovery of biomarkers. The challenge for FFPE shotgun proteomic analysis is preparation by an efficient and reproducible protocol, which includes protein extraction and digestion. In this study, we analyzed two different methods and evaluated their repeatabilities and efficiencies. We illustrated the reproducibility of the most efficient method, FFPE-FASP, by a pilot study on diverticulitis tissue and on FFPE samples amount accessible in hospital biobanks. These data showed that FFPE is suitable for use in clinical proteomics, especially when the FFPE-FASP method is combined with label-free shotgun proteomics as described in the workflow presented in this work. [less ▲]Detailed reference viewed: 44 (10 ULg)
El sindrome tirogastrico autoinmune : sus efectos sobre los micronutrientes y la tumorigenesis gastrica
VALDES SOCIN, Hernan Gonzalo ; LUTTERI, Laurence ; Cavalier, Etienne et al
in Revista Argentina de Endocrinologia y Metabolismo (2014), 51Detailed reference viewed: 31 (4 ULg)
Hypercalcémie réfractaire et sécrétion ectopique de calcitonine dans un cancer neuroendocrine du pancréas : Effets hypocalcémiants du Cinacalcet
VALDES SOCIN, Hernan Gonzalo ; LOLY, Jean-Philippe ; BETEA, Daniela et al
in Annales d'Endocrinologie (2013, October), 74Detailed reference viewed: 39 (9 ULg)
Thrombose portale étendue chez un patient sous anti-vitamine K
LEDOUBLE, Vinciane ; BECK, Emmanuel ; PETERS, Pierre et al
in Revue Médicale de Liège (2013), (68(7-8)), 382-6Detailed reference viewed: 43 (7 ULg)
Profile of pediatric Crohn's disease in Belgium.
; Mahachie John, Jestinah ; et al
in Journal of Crohn's & colitis (2013), 7(11), 588-98
AIM: A Belgian registry for pediatric Crohn's disease, BELCRO, was created. This first report aims at describing disease presentation and phenotype and determining associations between variables at ... [more ▼]
AIM: A Belgian registry for pediatric Crohn's disease, BELCRO, was created. This first report aims at describing disease presentation and phenotype and determining associations between variables at diagnosis and registration in the database. METHODS: Through a collaborative network, children with previously established Crohn's disease and newly diagnosed children and adolescents (under 18 y of age) were recruited over a 2 year period. Data were collected by 23 centers and entered in a database. Statistical association tests analyzed relationships between variables of interest at diagnosis. RESULTS: Two hundred fifty-five patients were included. Median age at diagnosis was 12.5 y (range: 1.6-18 y); median duration of symptoms prior to diagnosis was 3 m (range: 1-12 m). Neonatal history and previous medical history did not influence disease onset nor disease behavior. Fifty three % of these patients presented with a BMI z-score < -1. CRP was an independent predictor of disease severity. Steroids were widely used as initial treatment in moderate to severe and extensive disease. Over time, immunomodulators and biological were prescribed more frequently, reflecting a lower prescription rate for steroids and 5-ASA. A positive family history was the sole significant determinant for earlier use of immunosuppression. CONCLUSION: In Belgium, the median age of children presenting with Crohn's disease is 12.5 y. Faltering growth, extensive disease and upper GI involvement are frequent. CRP is an independent predictive factor of disease activity. A positive family history appears to be the main determinant for initial treatment choice. [less ▲]Detailed reference viewed: 55 (24 ULg)
National differences in ulcerative colitis experience and management among patients from five European countries and Canada: An online survey.
; ; LOUIS, Edouard et al
in Journal of Crohn’s and Colitis (2013), 7
BACKGROUND AND AIMS: Patients' and physicians' perceptions of ulcerative colitis and its management are important for developing and guiding appropriate therapies. This study explored national differences ... [more ▼]
BACKGROUND AND AIMS: Patients' and physicians' perceptions of ulcerative colitis and its management are important for developing and guiding appropriate therapies. This study explored national differences in patients' and physicians' experiences, expectations, and beliefs about ulcerative colitis. METHODS: Structured, cross-sectional, online surveys evaluating various indices were completed by 775 adult patients with ulcerative colitis and 475 physicians actively managing ulcerative colitis patients from France, Germany, Ireland, Spain, the United Kingdom, and Canada. RESULTS: Patients' classification of their symptom severity differed across countries (mild, 16%-45%; moderate, 46%-58%; severe, 4%-36%). Expectations of disease control also varied, with 26% (Ireland) to 65% (Spain) describing that remission realistically involves "living without symptoms." Within each country, more patients (45%-69%) than physicians (28%-45%) considered ulcerative colitis symptoms to affect patients' quality of life. Mean number of patient-reported flares during the past year ranged from 2.5 in Ireland to 8.0 in France. Self-reported adherence with oral 5-aminosalicylic acid (during remission) was highest in Spain (91% vs 50%-73% across other countries). Spanish patients were more likely to self-adjust their medications (54% vs 2%-5%), but reported the most dissatisfaction with therapy (42% vs 9%-27%). Irish patients were least likely to arrange physician/specialist nurse visits (14% vs 36%-49%) and least open to discussion of their condition. CONCLUSIONS: Important national differences in ulcerative colitis patients' attitudes and perceptions were observed, which may help physicians improve patient care based on country-specific needs and influence self-assessments in clinical trials. The results suggest a need for structured patient education to improve adherence and outcomes. [less ▲]Detailed reference viewed: 17 (2 ULg)
Adalimumab improves patient-reported outcomes and reduces indirect costs in patients with moderate to severe Crohn's disease: Results from the CARE trial.
LOUIS, Edouard ; ; et al
in Journal of Crohn’s and Colitis (2013), 7
BACKGROUND AND AIMS: Crohn's disease negatively affects patients' quality of life and ability to work. We investigated the impact of adalimumab on work productivity, daily activities, and quality of life ... [more ▼]
BACKGROUND AND AIMS: Crohn's disease negatively affects patients' quality of life and ability to work. We investigated the impact of adalimumab on work productivity, daily activities, and quality of life in an open-label trial (N=945). The population comprised both infliximab-naive and -exposed patients, including infliximab primary non-responders. METHODS: Patients received adalimumab induction therapy (160mg/80mg at Weeks 0/2), followed by adalimumab 40mg every other week for up to 20weeks (patients with flares/non-response could receive 40mg weekly at/after Week 12). The Work Productivity and Activity Impairment Questionnaire and Short Inflammatory Bowel Disease Questionnaire were assessed. Indirect cost savings were estimated based on the average work productivity improvements at Week 20. RESULTS: Mean baseline scores indicated severe productivity impairment and poor quality of life. At Week 20, 60% of infliximab-naive and 47% of infliximab primary non-responders achieved clinically important improvements (>/=9 points) on the Short Inflammatory Bowel Disease Questionnaire, and 51% and 43%, respectively, achieved the minimum clinically important difference (improvement >/=7 percentage points) for total work productivity impairment (non-responder imputation). At Week 20, 64% of infliximab-naive and 55% of infliximab primary non-responders achieved clinically important improvements in total activity impairment. Estimated 20-week total indirect productivity-related cost savings were euro3070 per infliximab-naive patient and euro2059 per infliximab-exposed patient. CONCLUSIONS: Adalimumab therapy significantly improved work productivity and disease-specific quality of life for patients with moderate to severe Crohn's disease. Patients who failed prior infliximab therapy and patients naive to infliximab benefited from adalimumab, with potentially greater benefits for infliximab-naive patients (NCT00409617). [less ▲]Detailed reference viewed: 15 (1 ULg)
Adalimumab dose escalation and dose de-escalation success rate and predictors in a large national cohort of Crohn's patients.
; ; 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 ▲]Detailed reference viewed: 19 (4 ULg)
Commentary: predicting complicated Crohn's disease and surgery--phenotypes, genetics, serology and psychological characteristics of a population-based cohort.
; LOUIS, Edouard
in Alimentary pharmacology & therapeutics (2013), 38(5), 555-6Detailed reference viewed: 26 (8 ULg)
Vedolizumab as induction and maintenance therapy for Crohn's disease.
; ; 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 ▲]Detailed reference viewed: 28 (1 ULg)
FDG PET/CT in Crohn's disease: correlation of quantitative FDG PET/CT parameters with clinical and endoscopic surrogate markers of disease activity.
; ; 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 ▲]Detailed reference viewed: 20 (3 ULg)
Maladie de Crohn et entero-IRM evaluation de l'activite de la maladie et du dommage tissulaire.
; Louis, Edouard ;
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 ▲]Detailed reference viewed: 61 (10 ULg)
Serum adalimumab concentration and clinical remission in patients with Crohn's disease.
; ; 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 ▲]Detailed reference viewed: 9 (1 ULg)
Role of endoscopy, cross-sectional imaging and biomarkers in Crohn's disease monitoring.
; Meuwis, Marie-Alice ; 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 ▲]Detailed reference viewed: 25 (3 ULg)
Strategic use of immunosuppressants and anti-TNF in inflammatory bowel disease.
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 ▲]Detailed reference viewed: 30 (6 ULg)
Consecutive fecal calprotectin measurements to predict relapse in patients with ulcerative colitis receiving infliximab maintenance therapy.
; Louis, Edouard ; 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 ▲]Detailed reference viewed: 9 (1 ULg)
Serum calprotectin as a biomarker for Crohn's disease.
Meuwis, Marie-Alice ; ; 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 ▲]Detailed reference viewed: 14 (2 ULg)
Evolving definitions of remission in Crohn's disease.
; ; Louis, Edouard 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 ▲]Detailed reference viewed: 11 (0 ULg)