Ulla Turunen

Crohn's Disease Activity Assessed by Fecal Calprotectin and Lactoferrin : Correlation with Crohn's Disease Activity Index and Endoscopic Findings

Background: Correlation of endoscopic Crohns disease activity with fecal calprotectin and lactoferrin is insufficiently studied. We evaluated the clinical significance of these neutrofil‐derived proteins in assessment of Crohns disease activity by comparing them with endoscopic disease activity and with Crohns disease activity index (CDAI) and serum CRP. Methods: A total of 77 CD patients underwent one or more ileocolonoscopies (n = 106) with scoring of Crohns disease index of severity (CDEIS). Patients provided stool samples for calprotectin and lactoferrin measurements and blood samples for CRP. Clinical activity was based on the CDAI. Results: Both fecal calprotectin and lactoferrin correlated significantly with CDEIS (Spearmans r 0.729 and 0.773, P < 0.001). With a cutoff level of 200 &mgr;g/g for a raised fecal calprotectin concentration, sensitivity was 70%, specificity 92%, positive predictive value (PPV) 94%, and negative predictive value (NPV) 61% in predicting endoscopically active disease (CDEIS ≥ 3). A fecal lactoferrin concentration of 10 &mgr;g/g as the cutoff value gave a sensitivity, specificity, PPV, and NPV of 66%, 92%, 94%, and 59%. Sensitivity of CDAI ≥ 150 to detect endoscopically active disease was only 27%, specificity 94%, PPV 91%, and NPV 40%. A raised serum CRP (> 5 mg/l) gave a sensitivity, specificity, PPV, and NPV of 48%, 91%, 91%, and 48%. Conclusions: For evaluation of Crohns disease activity, based on endoscopic findings, more sensitive surrogate markers than is CDAI or CRP are fecal calprotectin and lactoferrin. These prove to be useful tools for estimation of disease activity in Crohns disease.

Correlation of faecal calprotectin and lactoferrin with an endoscopic score for Crohn's disease and histological findings

Backgroundu2002 Faecal calprotectin and lactoferrin increasingly serve as surrogate markers of disease activity in IBD. Data on the correlation of these markers with simple endoscopic score for Crohn’s disease (SES‐CD) and with histological findings are as yet limited.

Fecal calprotectin, lactoferrin, and endoscopic disease activity in monitoring anti‐TNF‐alpha therapy for Crohn's disease

Background: Fecal calprotectin and lactoferrin are promising noninvasive biomarkers for intestinal inflammation. In Crohns disease (CD), during anti‐TNF‐alpha (TNF‐&agr;) treatment, the clinical significance of these markers has, however, been insufficiently explored. Methods: Among CD patients receiving anti‐TNF‐&agr; therapy we assessed the role of fecal calprotectin and lactoferrin as surrogate markers for mucosal healing. Before and 3 months after the beginning of anti‐TNF‐&agr; induction, 15 patients underwent ileocolonoscopy with scoring of the Crohns Disease Index of Severity (CDEIS). Fecal samples for calprotectin and for lactoferrin measurements were collected and the Crohns Disease Activity Index (CDAI) was calculated at the time of the endoscopies and 2 and 8 weeks after the first treatment. Results: The median CDEIS fell from 13.0 to 4.8 (P = 0.002) and CDAI from 158 to 68 (P = 0.005). Accordingly, the median fecal calprotectin concentration fell from 1173 &mgr;g/g to 130 &mgr;g/g (P = 0.001) and fecal lactoferrin from 105.0 &mgr;g/g to 2.7 &mgr;g/g (P = 0.001). Of the 15 patients, 11 (73%) showed an endoscopic response to treatment and 5 of these achieved endoscopic remission (CDEIS < 3). In those 5 patients the fecal calprotectin concentration declined from 1891 &mgr;g/g (range 813–2434) to 27 &mgr;g/g (13–130) and lactoferrin from 92.4 &mgr;g/g (35.5–235.6) to 1.9 &mgr;g/g (0.0–2.1). Conclusions: Compared to pretreatment values, concentrations of fecal calprotectin and lactoferrin after the anti‐TNF‐&agr; treatment were significantly lower. During anti‐TNF‐&agr; therapy these fecal neutrophil‐derived proteins may thus be useful surrogate markers for mucosal healing.

Surrogate markers and clinical indices, alone or combined, as indicators for endoscopic remission in anti-TNF-treated luminal Crohn's disease

Abstract Objective. Endoscopically confirmed mucosal healing has become an important therapeutic goal in the treatment of Crohns disease (CD). The role of clinical indices, such as the Crohns disease activity index (CDAI) and the Harvey–Bradshaw index (HBI), and surrogate markers, such as C-reactive protein (CRP) and fecal calprotectin, to indicate remission determined by endoscopy needs to be clarified. We analyzed the role of surrogate markers and clinical indices, separately and in combination, by comparing them with endoscopically scored disease activity in biologically treated CD patients. Material and methods. Prospectively collected data of all patients with inflammatory bowel disease treated with tumor necrosis factor alpha antibodies in a tertiary center between 2007 and 2010. Altogether 210 endoscopies in 64 CD patients were analyzed. The simple endoscopic score for Crohns disease (SES-CD) was used for scoring disease activity and compared with available data on concurrent CDAI, HBI, CRP, and calprotectin. Results. Endoscopic activity demonstrated a stronger correlation with calprotectin and CRP than with the clinical indices. Neither the clinical indices nor CRP was reliable at identifying endoscopic remission. However, calprotectin alone identified endoscopic remission with a sensitivity of 84% and specificity of 74%, but was beaten, although not statistically significantly, by a combined index, based on calprotectin and the HBI. Conclusions. Clinical scores commonly used in the assessment of disease activity are unreliable at differentiating endoscopic remission from active CD. Despite this, a score based on a combination of fecal calprotectin and the HBI is a new promising tool for identifying endoscopic remission.

Endoscopic evaluation of Crohn's disease activity: Comparison of the CDEIS and the SES‐CD

Background: Few data exist of prospective parallel scoring of the validated endoscopic scores in Crohns disease (CD), Crohns Disease Index of Severity (CDEIS), and Simple Endoscopic Score for Crohns Disease (SES‐CD). Methods: Both the CDEIS and the SES‐D were scored immediately after each endoscopy of 86 CD patients referred for ileocolonoscopy in a cross‐sectional study. Furthermore, after CD therapy, 32 CD patients underwent a follow‐up endoscopy with scoring of the CDEIS and SES‐CD. Endoscopic scorings were graded as inactive, mild, moderate, or severe. Clinical activity was assessed with the Crohns Disease Activity Index (CDAI) and serum C‐reactive protein (CRP) was measured. Results: The SES‐CD correlated with the CDEIS significantly (Spearmans r = 0.938, P < 0.0001). Weaker correlations were detected between the SES‐CD and the CDAI (r = 0.473) or CRP (r = 0.525, both P < 0.0001). Grading of SES‐CD from inactive to severe correlated significantly with grading of the CDEIS (r = 0.859, P < 0.0001). Changes between baseline and follow‐up endoscopy scores correlated significantly (r = 0.828 between delta‐CDEIS and delta‐SES‐CD, P < 0.001), but failed to correlate with delta‐CDAI or delta‐CRP (all P > 0.05). Conclusions: Both validated endoscopic scores, the CDEIS and SES‐CD, and their changes during CD therapy demonstrated a close correlation. For scoring of endoscopic activity in clinical routine, the SES‐CD could replace the CDEIS. Inflamm Bowel Dis 2010

Increased risk for coronary heart disease, asthma, and connective tissue diseases in inflammatory bowel disease

BACKGROUND AND AIMSnPatients with inflammatory bowel diseases (IBD) show increased risk for other immune-mediated diseases such as arthritis, ankylosing spondylitis, and some pulmonary diseases. Less is known about the prevalence of other chronic diseases in IBD, and the impact of comorbidity on health-related quality of life (HRQoL).nnnMETHODSnThe study population comprised 2831 IBD patients recruited from the National Health Insurance register and from a patient-association register. Study subjects completed generic 15D and disease-specific IBDQ questionnaires. The Social Insurance Institution of Finland provided data on other chronic diseases entitling patients to reimbursed medication. For each study subject, two controls, matched for age, sex, and hospital district, were chosen.nnnRESULTSnA significant increase existed in prevalence of connective tissue diseases, pernicious anemia and asthma. Furthermore, coronary heart disease (CHD) occurred significantly more frequently in IBD patients than in their peers (p=0.004). The difference was, however, more clearly seen in females (p=0.014 versus 0.046 in males). Active and long-lasting IBD were risk factors. Concomitant other chronic diseases appeared to impair HRQoL. Asthma, hypertension and psychological disorders had an especially strong negative impact on HRQoL, as observed with both the generic and disease-specific HRQoL tools.nnnCONCLUSIONSnIn addition to many immune-mediated diseases, CHD appeared to be more common in IBD than in control patients, especially in females. The reason is unknown, but chronic inflammation may predispose to atherosclerosis. This finding should encourage more efficacious management of underlying cardiovascular risk factors, and probably also inflammatory activity in IBD.

Mucosal healing at 3 months predicts long-term endoscopic remission in anti-TNF-treated luminal Crohn's disease

Abstract Background and aims. Studies performed on patient and disease characteristics predicting the treatment response in tumor necrosis factor alpha antibody (anti-TNF)-treated Crohns disease (CD) have generally been based on clinical data. Only a few studies have assessed the role of endoscopy as a predictor for long-term response for anti-TNF therapy. Our aim was to evaluate the role of early endoscopy in predicting the long-term endoscopic response to anti-TNF in active luminal CD in a clinical setting. Patients and methods. Forty-two patients with active luminal CD, treated for at least 3 months with anti-TNF, either adalimumab (52%) or infliximab (48%), were included in this prospective study. Data on the simple endoscopic score for Crohns disease (SES-CD) at 3 months after therapy commencement, and either data on the SES-CD or surgery after 1 year, were available for all patients. Endoscopic remission was defined as SES-CD 0−2. Results. At 3 months after commencing anti-TNF therapy, 10 patients (24%) were in endoscopic remission. Thirty-three patients continued anti-TNF as maintenance therapy. At 1 year, endoscopic remission (11/33, 33%) was significantly more common in those patients who had been in endoscopic remission at 3 months, compared with those with endoscopically active disease at 3 months (7/10, 70% vs. 4/23, 17%, p = 0.01). The 3-month SES-CD had a sensitivity of 88%, and specificity of 64%, to predict 1-year endoscopic remission in patients who received anti-TNF maintenance therapy. Conclusions. In anti-TNF-treated active luminal CD mucosal healing at 3 months is a strong predictor for long-term endoscopic response.

Impact of demographic factors, medication and symptoms on disease-specific quality of life in inflammatory bowel disease

ObjectivesTo investigate the relation of demographic factors, medication and symptoms to health-related quality of life in patients with inflammatory bowel disease, and to identify patients in need of special support.MethodsA questionnaire packet comprising the Inflammatory Bowel Disease Questionnaire (IBDQ) and the European Federation of Crohn’s and Colitis Associations’ (EFCCA) Survey Questionnaire was sent to 3,852 adult members of the Crohn and Colitis Association of Finland. IBDQ was used for measuring health-related quality of life (HRQoL), and the EFCCA questionnaire gave information about demographics, symptoms and medication.ResultsAltogether 2,386 questionnaires (62%) were available for analysis. Patients reporting symptoms affecting leisure activities or work had significantly lower total IBDQ scores (indicating worse HRQoL) than patients with less disturbing symptoms. Satisfaction with current therapy, female gender and age affected the scores. Subjects who had undergone surgery scored lower than those who had not. Patients currently receiving corticosteroids and newly diagnosed patients had lower scores than other patients.ConclusionsIn everyday practice, paying attention to and reducing patients’ symptoms and their impact on daily life is important when aiming at improving HRQoL. Special attention should be given to patients who have undergone surgery, and to newly diagnosed patients.

Endoscopic monitoring of infliximab therapy in Crohn's disease†

Background: So far, infliximab (IFX) therapy for the treatment of Crohns disease (CD) has generally been guided by clinical symptoms. Data on treatment response as ascertained by endoscopy in IFX therapy are scarce. The aims of this study were to measure the endoscopic response rate during IFX induction and maintenance therapy in luminal CD, and also evaluate the role of endoscopy in monitoring IFX therapy. Methods: Data obtained from 71 patients with active luminal CD and treated with IFX were analyzed retrospectively. The endoscopy findings were scored according to mucosal activity as: 0 (remission), 1–2 (mild), 3–4 (moderate), and 5–6 (severe). A positive endoscopic response was determined by a decrease in score of at least two points and mucosal healing was assigned a score of between 0–2. Results: At baseline all patients presented with moderate or severe luminal inflammation. A positive endoscopic response occurred in 73% of patients at 3 months and when IFX was continued, the endoscopic response was maintained in 77% of these patients at 12 months. Mucosal healing at first follow‐up endoscopy was documented in 45% of patients and was highly predictive for its persistence at 12 months, maintained in 90% of patients, when IFX was continued. Conclusions: Endoscopy at 3 months from the start of IFX therapy helps to predict responders to IFX for maintenance therapy in active luminal CD. (Inflamm Bowel Dis 2011)

Health-related quality of life in inflammatory bowel disease measured with the generic 15D instrument

ObjectivesIn many surveys, inflammatory bowel disease (IBD) has been shown to have a negative impact on health-related quality of life (HRQoL), especially when the disease is active. The purpose of this study was to compare a disease-specific HRQoL tool (Inflammatory Bowel Disease Questionnaire, IBDQ) and a generic HRQoL tool (15D) in a large cohort of IBD patients, to assess the ability of the 15D to detect differences in HRQoL between disease states and to compare the HRQoL of IBD patients with that of the general population.MethodsThe study population comprised 2,931 IBD patients over 18 picked from a national Social Insurance Institute register and from a patient organization register. The 15D data for the general population came from the National Health 2000 Health Examination Survey.ResultsFor patients with IBD, the 15D tool was feasible and had good discriminatory power. The total 15D score was significantly higher among patients with less active disease estimated by frequency of IBD symptoms and was strongly correlated with total IBDQ score. The general population scored significantly higher than did the study subjects on most of the 15D dimensions.ConclusionsThe 15D was a fast and easy-to-apply method for the examination of HRQoL in IBD patients. In addition to HRQoL studies it could be used in everyday practice as well. Patients with IBD have worse HRQoL than do gender- and age-standardized controls.