Katrine Carlsen

Fecal Calprotectin Measured By Patients at Home Using Smartphones—A New Clinical Tool in Monitoring Patients with Inflammatory Bowel Disease

Background:Fecal calprotectin is a reliable noninvasive marker for intestinal inflammation usable for monitoring patients with inflammatory bowel disease. Tests are usually performed by enzyme-linked immunosorbent assay (ELISA), which is time consuming and delays results, thus limiting its use in clinical practice. Our aim was to evaluate CalproSmart, a new rapid test for fecal calprotectin performed by patients themselves at home, and compare it to gold standard ELISA. Methods:A total of 221 patients with inflammatory bowel disease (115 ulcerative colitis and 106 Crohns disease) were included. The CalproSmart test involves extraction of feces, application to the lateral flow device, and taking a picture with a smartphone after 10 minutes of incubation. Results appear on the screen within seconds. Patients were instructed at inclusion and had a video guide of the procedure as support. When using CalproSmart at home, patients also sent in 2 fecal samples to be analyzed by ELISA. Results:Totally, 894 fecal calprotectin results were obtained by ELISA, and 632 of them from CalproSmart. The correlation coefficient was 0.685, higher for academics than nonacademics (0.768 versus 0.637; P = 0.0037). The intra-assay and interassay coefficients of variation of the CalproSmart test were 4.42% and 12.49%, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value were 82%, 85%, 47%, and 97%, respectively, with an optimal cutoff at 150 &mgr;g/g. Conclusions:The CalproSmart test performed by patients with inflammatory bowel disease for fast assessment of gut inflammation seems a reliable alternative to ELISA and presents a new way of monitoring patients by eHealth.

Using eHealth strategies in delivering dietary and other therapies in patients with irritable bowel syndrome and inflammatory bowel disease

Health‐care systems around the world are facing increasing costs. Non‐adherent, chronically ill patients are one such expense incurred by health‐care providers. Web‐based home‐monitoring of patients—or eHealth—has been shown to increase adherence to medical therapy, facilitate contact between patients and health‐care professionals, and reduce time to remission for patients with inflammatory bowel disease (IBD). Web‐based treatment is a supportive tool for the health‐care provider in an out‐patient clinic. eHealth web‐programs, such as the Constant Care application, visualize disease activity in a traffic light system and empower patients to screen for disease activity, enabling them to respond appropriately to their symptoms. The eHealth screening procedure for monitoring both pediatric and adult IBD patients is based on a self‐obtained symptom score, together with a fecal biomarker for inflammation (fecal calprotectin) that the patients can measure independently using their smart phone, providing both patient and physician with an immediate disease status that they can react to instantaneously. Likewise, web applications for IBD patients, web applications for irritable bowel syndrome (IBS) patients and also IBD patients with co‐existing IBS, have proven valuable for monitoring and treating IBS symptoms with a diet low in fermentable oligo‐, di‐, monosaccharides and polyols (low‐FODMAP diet). With careful disease monitoring via the web application and increased patient adherence, eHealth might be capable of improving the natural disease course of IBD and IBS.

Self-managed ehealth Disease Monitoring in Children and Adolescents with Inflammatory Bowel Disease: A Randomized Controlled Trial.

Background: To evaluate the impact of eHealth on disease activity, the need for hospital contacts, and medical adherence in children and adolescents with inflammatory bowel disease (IBD). Furthermore, to assess eHealths influence on school attendance and quality of life (QoL). Methods: Patients with IBD, 10 to 17 years attending a public university hospital, were prospectively randomized to a 2-year open label case-controlled eHealth intervention. The eHealth-group used the web-application young.constant-care.com (YCC) on a monthly basis and in case of flare-ups, and were seen at one annual preplanned outpatient visit. The control-group continued standard visits every third month. Every 3 months, both groups had blood and fecal calprotectin tested and the following were assessed: escalation in medication, disease activity, hospital contacts, medical adherence, school absence, and QoL. Results: Fifty-three patients in nonbiological treatment were included (27 eHealth/26 control). We found no differences between the groups regarding escalation in treatment and disease activity (symptoms, fecal calprotectin, and blood). The number of total outpatient visits (mean: eHealth 3.26, SEM 0.51; control 7.31, SEM 0.69; P < 0.0001) and IBD-related school absence (mean days: eHealth 1.6, SEM 0.5; control 16.5, SEM 4.4; P < 0.002) was significantly lower in the eHealth-group. No differences in medical adherence and QoL were found. Adherence to YCC was 81% (384 of the 475 expected entries). None of the patients or parents felt unsafe using the eHealth system. Conclusions: The use of eHealth in children and adolescents with IBD is feasible, does not lead to impaired disease control, and can be managed by the patients without risk of increased disease activity.

Individualized Infliximab Treatment Guided by Patient-managed ehealth in Children and Adolescents with Inflammatory Bowel Disease

Background: To individualize timing of infliximab (IFX) treatment in children and adolescents with inflammatory bowel disease (IBD) using a patient-managed eHealth program. Methods: Patients with IBD, 10 to 17 years old, treated with IFX were prospectively included. Starting 4 weeks after their last infusion, patients reported a weekly symptom score and provided a stool sample for fecal calprotectin analysis. Based on symptom scores and fecal calprotectin results, the eHealth program calculated a total inflammation burden score that determined the timing of the next IFX infusion (4–12 wk after the previous infusion). Quality of Life was scored by IMPACT III. A control group was included to compare trough levels of IFX antibodies and concentrations and treatment intervals. Patients and their parents evaluated the eHealth program. Results: There were 29 patients with IBD in the eHealth group and 21 patients with IBD in the control group. During the control period, 94 infusions were provided in the eHealth group (mean interval 9.5 wk; SD 2.3) versus 105 infusions in the control group (mean interval 6.9 wk; SD 1.4). Treatment intervals were longer in the eHealth group (P < 0.001). Quality of Life did not change during the study. Appearance of IFX antibodies did not differ between the 2 groups. Eighty percent of patients reported increased disease control and 63% (86% of parents) reported an improved knowledge of the disease. Conclusions: Self-managed, eHealth-individualized timing of IFX treatments, with treatment intervals of 4 to 12 weeks, was accompanied by no significant development of IFX antibodies. Patients reported better control and improved knowledge of their IBD.

F-calprotectin and blood markers correlate to Quality of Life in Pediatric Inflammatory Bowel Disease.

Objectives: Our aim was to investigate predictors of health-related quality of life (HRQoL) with respect to changes in disease parameters over time in children with inflammatory bowel disease. Methods: This was a prospective longitudinal study examining the association between HRQoL (IMPACT III) and symptom scores (Pediatric Crohn Disease Activity Index, abbreviated Pediatric Ulcerative Colitis Activity Index), fecal calprotectin measures and blood analyses (C-reactive protein, erythrocyte sedimentation rate, orosomucoid, albumin, hemoglobin, and vitamin-D) in a cohort of 10- to 17-year-old patients with inflammatory bowel disease. Data were collected prospectively at 3-month intervals during a 2-year period. Associations were analyzed using linear mixed-effect models. Patients were divided into 2 groups, which received nonbiological oral treatment or biological parenteral treatment. Results: From 79 patients (39 Crohn disease/40 ulcerative colitis), representing a total of 43,132 days of observation, 572 IMPACT measurements were paired with variables. A decrease in the IMPACT III score was significantly associated with increased ulcerative colitis-symptom score in the biological group (P = 0.005), and a similar inverse tendency was found in the nonbiological group and for Crohn disease symptoms in both groups. We found in both treatment groups overall a significant (P < 0.05) inverse association between the IMPACT III and the levels of fecal calprotectin, erythrocyte sedimentation rate, and orosomucoid, whereas albumin, hemoglobin, and vitamin-D were directly significantly associated. Conclusions: The IMPACT score, already known to correlate with disease activity, has now been shown to be associated with disease markers in feces and blood. This emphasizes that objective markers of disease activity indirectly can predict the patients HRQoL.

Sa1245 Gut Microbiota in IBD Patients With IBS Before and After 6 Weeks of Low FODMAP Diet

Background: Glucocorticoids (GCs) are steroid hormones used to induce remission in moderate-to-severe inflammatory bowel disease (IBD). A substantial fraction of patients do not respond to GC treatment and require alternate therapies or surgery. At present, nonresponse can only be assessed empirically by observing continued disease activity. Aim: To identify biomarkers of GC response in IBD patients and provide insights into the biological processes underlying variation in clinical response to GCs. Methods: 18 GC-responsive and 18 GC-nonresponsive IBD patients were retrospectively recruited from our IBD Center. This sample included 14 patients with ulcerative colitis (UC) and 22 patients with Crohns disease (CD), all previously treated with oral or intravenous steroids. In peripheral blood mononuclear cells from each patient, we performed in vitro assays to measure GC inhibition of three different immune stimulants (phytohemagglutinin [PHA], α-CD3/α-CD28, and lipopolysaccharide [LPS]) controlling for age, gender, ethnicity, and current medications. Results: In both diseases, we found that inhibition of PHA-mediated T cell proliferation was significantly associated with clinical response (P=0.04). Inhibition of proliferation due to direct T cell receptor stimulation using α-CD3/α-CD28 was also significantly associated with clinical response in UC patients (P=0.009) (Figure 1), but not in CD patients (P=0.78). Interestingly, inhibition of LPS-mediated cytokine secretion showed the strongest association with clinical response across both diseases (P=0.005) (Figure 2). Conclusions: Extending on previously observed associations between inhibition of PHA and α-CD3/α-CD28-mediated proliferation and clinical response, we show that inhibition of LPS stimulation shows an even stronger association with clinical response to GCs in patients with IBD. These results are consistent with the importance of bacterial recognition and innate immunity in the etiology of IBD. This assay could be a powerful predictor of clinical response and future studies are needed in order to replicate these observations.

Occurrence of anaemia in the first year of inflammatory bowel disease in a European population-based inception cohort: An ECCO-EpiCom study

Background and aims Anaemia is an important complication of inflammatory bowel disease [IBD]. The aim of this study was to determine the prevalence of anaemia and the practice of anaemia screening during the first year following diagnosis, in a European prospective population-based inception cohort. Methods Newly diagnosed IBD patients were included and followed prospectively for 1 year in 29 European and one Australian centre. Clinical data including demographics, medical therapy, surgery and blood samples were collected. Anaemia was defined according to the World Health Organization criteria. Results A total of 1871 patients (Crohns disease [CD]: 686, 88%; ulcerative colitis [UC]: 1,021, 87%; IBD unclassified [IBDU] 164. 81%) were included in the study. The prevalence of anaemia was higher in CD than in UC patients and, overall, 49% of CD and 39% of UC patients experienced at least one instance of anaemia during the first 12 months after diagnosis. UC patients with more extensive disease and those from Eastern European countries, and CD patients with penetrating disease or colonic disease location, had higher risks of anaemia. CD and UC patients in need of none or only mild anti-inflammatory treatment had a lower risk of anaemia. In a significant proportion of patients, anaemia was not assessed until several months after diagnosis, and in almost half of all cases of anaemia a thorough work-up was not performed. Conclusions Overall, 42% of patients had at least one instance of anaemia during the first year following diagnosis. Most patients were assessed for anaemia regularly; however, a full anaemia work-up was frequently neglected in this community setting.

P433 Is e-Health, web-based monitoring and treatment, useful for children and adolescents with inflammatory bowel disease? – a paediatric clinical trial

Background: Cholangiocarcinoma (CC) complicates in 10 20% of the patients with dominant stricture (DS) in patients with primary sclerosing cholangitis (PSC) related with inflammatory bowel diseases (IBD). Methods: We investigated 2200 patients with IBD for PSC with DS. Results: PSC was diagnosed in 41 pts (1.6%). Of the 41 pts with PSC, DS was diagnosed in 14 (34%); 64% were male, and followed for a mean of 4.86 yrs (0 13 yrs). Main finding was pruritis alone in 64% pts with DS as in 15% without DS (p = 0.003). The diagnose date of both IBD and PSC was younger in pts with DS than without DS (36.9 yrs vs. 38.1 and 40.2 yrs vs. 41.1 yrs; p > 0.05, respectively). Only current ALP and GGT levels were differ between the groups (p: 0.003 and p: 0.001, respectively). In this study, ERCP performed in 22 pts with PSC and was the main diagnostic tool for the questioning the occurence of DS (p = 0.011), besides CT, MRI and liver bx. ERCP usually performed more than once. EST and baloon dilation performed in all pts with stenting in 9 pts. Brush cytology performed only in 3 pts with strong suspicious for CC and benign pathology reported. IBD disease duration was longer in pts without DS than with DS (10.4 yrs vs. 8.1 yrs, p > 0.05). During the follow-up, 2 patients dead due to the causes other than CC; one due to endstage liver disease, and one had back wash ileitis complicated with colon malignancy and later died. Liver transplantation performed twice in one patient and still alive and in a good condition. At the same time, we evaluated our last 5-years pathology records for CC in a different study, and found 19 cases. None was related with our IBD or PSC-IBD group. Of the 19, colonoscopy performed in 5, and showed no IBD on biopsy. Conclusions: In our series, dominant strictures with PSC related with IBD showed a relatively benign nature differently from the current literature.

The sensitivity of fecal calprotectin in predicting deep remission in ulcerative colitis

Abstract Background: Mucosal healing is proposed as treat-to-target in ulcerative colitis (UC), even though the definition of mucosal healing remains contested as it has been suggested to be assessed by either endoscopy, histology or both. However, all definitions require an endoscopic evaluation of the mucosa. As endoscopies are invasive and uncomfortable to the patient we aimed to calibrate noninvasive predictors of mucosal inflammatory status defined by both endoscopy and histology. Methods: UC patients (n = 106) undergoing a sigmoid-/colonoscopy were prospectively included. Feces (fecal calprotectin, FC), blood samples (hemoglobin, C-reactive protein, orosomucoid, erythrocyte sedimentation rate, albumin) and symptom scores (Simple Clinical Colitis Activity Index, SSCAI) were collected and analyzed. The colonic mucosa was assessed by the Mayo endoscopic sub score and biopsies were obtained for a histologic grading by Geboes score. Predictive cutoff values were analyzed by receiver operating characteristics (ROC). A combined endoscopic and histologic assessment defined deep remission (Mayo =0 and Geboes ≤1) and activity (Mayo ≥2 and Geboes >3). Results: Only FC showed a significant ROC curve (p < .05). We suggest FC (mg/kg) cutoffs for detection of following: Deep remission: FC ≤25; Indeterminate: FC 25-230 – an endoscopy is recommended if a comprehensive status of both endoscopic and histologic assessed activity is needed; Active disease: FC >230. The complete ROC data is presented, enabling extraction of an FC cutoff value’s sensitivity and specificity. Conclusions: FC predicts endoscopic and histologic assessed deep remission and inflammatory activity of colon mucosa. Neither the markers in blood nor the SCCAI performed significant ROC results.

Evaluation of Quality of Life in Crohn’s Disease and Ulcerative Colitis: What Is Health-Related Quality of Life?

While good Quality of Life (QoL) has long been a policy goal in the treatment of inflammatory bowel disease (IBD), adequate definition and measurement of it have remained elusive. The term “quality of life” is used to describe the general well-being of individuals in the field of healthcare. QoL should not be confused with “standard of living,” a term defined primarily by income. Instead, standard indicators of QoL include not only wealth and employment, but also the built environment, physical and mental health, education, recreation and leisure time, and social belonging. Health-related quality of life (HRQoL) is a subjective measure of a person’s physical and psychological well-being and represents a patient’s assessment of how a particular disease or intervention has affected their life.