A Patient Self-Made Point-of-Care Fecal Test Improves Diagnostic Accuracy Compared with Fecal Calprotectin Alone in Inflammatory Bowel Disease Patients

Background: Monitoring inflammatory bowel disease patients may be challenging. Fecal calprotectin is one of the most performed tests. Other fecal biomarkers are less used in clinical practice. Rapid fecal tests that could be performed by patients may be a useful strategy to closely monitor disease activity. Methods: We performed a prospective observational study including consecutive inflammatory bowel disease patients referred for colonoscopy in a single center. Certest FOB + Transferrin + Calprotectin + Lactoferrin® (Certest Biotec S.L, Zaragoza, Spain), a one-step point-of-care test which simultaneously detects these four biomarkers was performed. Endoscopic inflammatory activity was defined using the Mayo score (≥1) in ulcerative colitis, SES-CD (>3) and Rutgeerts scores (≥1) for Crohn’s disease. Results: Out of a total of 106 patients (56.5% female, mean age 51 years), 54 (50.9%) were diagnosed with ulcerative colitis and 52 (49.1%) with Crohn’s disease. Endoscopic activity was detected in 42 patients (39.0%). Fecal calprotectin provided the best sensitivity (97.6%), with limited specificity (34.4%). Compared to calprotectin, the other 3 fecal biomarkers showed better specificity (87.5–92.1%) and lower sensitivity (45.2–59.5%). Patients with a negative result in all biomarkers (19/106—17.9%) had 100% (CI 95% 97.4–100) negative predictive value, while patients with the 4 biomarkers positive (13/106—12.3%) had 100% (CI 95% 96.1–100) positive predictive value of endoscopic inflammatory activity. AUROC of this 4 biomarker point-of-care test was 0.845 (95% CI 0.771–0.920), significantly higher than the AUROCs of any of the 4 biomarkers. Conclusions: This test may be a useful strategy to monitor inflammatory activity in clinical practice by excluding or prioritizing patients in need of a colonoscopy.

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Predicting disease course in ulcerative colitis using stool proteins identified through an aptamer-based screen

Nature Communications ◽

10.1038/s41467-021-24235-0 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Sanam Soomro ◽

Suresh Venkateswaran ◽

Kamala Vanarsa ◽

Marwa Kharboutli ◽

Malavika Nidhi ◽

...

Keyword(s):

Ulcerative Colitis ◽

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Fecal Calprotectin ◽

Disease Monitoring ◽

Disease Course ◽

Lipocalin 2 ◽

Time Points ◽

Inflammatory Bowel ◽

Stool Samples

AbstractIn the search for improved stool biomarkers for inflammatory bowel disease (IBD), an aptamer-based screen of 1129 stool proteins was conducted using stool samples from an IBD cohort. Here we report that of the 20 proteins subsequently validated by ELISA, stool Ferritin, Fibrinogen, Haptoglobin, Hemoglobin, Lipocalin-2, MMP-12, MMP-9, Myeloperoxidase, PGRP-S, Properdin, Resistin, Serpin A4, and TIMP-1 are significantly elevated in both ulcerative colitis (UC) and Crohn’s disease (CD) compared to controls. When tested in a longitudinal cohort of 50 UC patients at 4 time-points, fecal Fibrinogen, MMP-8, PGRP-S, and TIMP-2 show the strongest positive correlation with concurrent PUCAI and PGA scores and are superior to fecal calprotectin. Unlike fecal calprotectin, baseline stool Fibrinogen, MMP-12, PGRP-S, TIMP-1, and TIMP-2 can predict clinical remission at Week-4. Here we show that stool proteins identified using the comprehensive aptamer-based screen are superior to fecal calprotectin alone in disease monitoring and prediction in IBD.

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Frequency of equivocation in surgical meta-evidence: a review of systematic reviews within IBD literature

BMJ Open ◽

10.1136/bmjopen-2017-018715 ◽

2017 ◽

Vol 7 (12) ◽

pp. e018715 ◽

Cited By ~ 3

Author(s):

John D Delaney ◽

John T Holbrook ◽

Robert K Dewar ◽

Patrick J Laws ◽

Alexander F Engel

Keyword(s):

Ulcerative Colitis ◽

Inflammatory Bowel Disease ◽

Crohn’S Disease ◽

Clinical Practice ◽

Systematic Reviews ◽

Bowel Disease ◽

Predisposing Factors ◽

Significant Difference ◽

Inflammatory Bowel ◽

Level 1

ObjectiveTo assess the level of equivocation among level 1 evidence in ulcerative colitis and Crohn’s disease and determine whether any predisposing factors are present.MethodMEDLINE, Embase, CINHAL and Cochrane were searched from 2006 to 2017. Papers were scored using AMSTAR and categorised into surgical (S), medical (M) or medical and surgical (MS) groups. The ability of each paper to make a recommendation and conclusiveness in doing so was recorded.Results278 papers were assessed. 82% (n=227) could make a recommendation, 18% (n=51) could not. There was a significant difference in ability to provide a recommendation between S and M (P=0.003) but not MS and M (P=0.022) nor S and MS (P=0.79). Where a recommendation was made, S papers were more likely to be tempered than M papers (P=0.014) but not MS papers (P=0.987).ConclusionsSurgical meta-evidence within the inflammatory bowel disease domain is more than twice as likely as medical meta-evidence to be unable to provide a recommendation for clinical practice. Where a recommendation was made, surgical reviews were twice as likely to temper their conclusion.

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Surrogate Fecal Biomarkers in Inflammatory Bowel Disease: Rivals or Complementary Tools of Fecal Calprotectin?

Inflammatory Bowel Diseases ◽

10.1093/ibd/izx011 ◽

2017 ◽

Vol 24 (1) ◽

pp. 78-92 ◽

Cited By ~ 17

Author(s):

Mirko Di Ruscio ◽

Filippo Vernia ◽

Antonio Ciccone ◽

Giuseppe Frieri ◽

Giovanni Latella

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Intestinal Inflammation ◽

Fecal Calprotectin ◽

Response To Therapy ◽

Polymorphonuclear Neutrophil ◽

Cochrane Library ◽

Clinical Relapse ◽

Inflammatory Bowel ◽

Fecal Biomarkers

Abstract Background Current noninvasive methods for assessing intestinal inflammation in inflammatory bowel disease (IBD) remain unsatisfactory. Along with C-reactive protein and erythrocyte sedimentation rate, fecal calprotectin (FC) is the standard test for assessing IBD activity, even though its specificity and accuracy are not optimal and it lacks a validated cutoff. Over the past few decades, several fecal markers released from intestinal inflammatory cells have been investigated in IBD; they are the subject of this systematic review. Methods A systematic electronic search of the English literature up to April 2017 was performed using Medline and the Cochrane Library. Only papers written in English that analyzed fecal biomarkers in IBD were included. In vitro studies, animal studies, studies on blood/serum samples, and studies analyzing FC or fecal lactoferrin alone were excluded. Results Out of 1023 citations, 125 eligible studies were identified. Data were grouped according to each fecal marker including S100A12, high-mobility group box 1, neopterin, polymorphonuclear neutrophil elastase, fecal hemoglobin, alpha1-antitrypsin, human neutrophil peptides, neutrophil gelatinase-associated lipocalin, chitinase 3-like-1, matrix metalloproteinase 9, lysozyme, M2-pyruvate kinase, myeloperoxidase, fecal eosinophil proteins, human beta-defensin-2, and beta-glucuronidase. Some of these markers showed a high sensitivity and specificity and correlated with disease activity, response to therapy, and mucosal healing. Furthermore, they showed a potential utility in the prediction of clinical relapse. Conclusions Several fecal biomarkers have the potential to become useful tools complementing FC in IBD diagnosis and monitoring. However, wide variability in their accuracy in assessment of intestinal inflammation suggests the need for further studies.

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P503 Rapid point-of-care monitoring of anti-infliximab antibodies in patients with inflammatory bowel disease treated with the reference infliximab or CT-P13 in routine clinical practice

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjx002.627 ◽

2017 ◽

Vol 11 (suppl_1) ◽

pp. S335-S336 ◽

Cited By ~ 1

Author(s):

A. Ametzazurra ◽

N. Rivera ◽

A.M. Hernández ◽

M.P. Arreba ◽

E. Ruiz ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Clinical Practice ◽

Bowel Disease ◽

Point Of Care ◽

Routine Clinical Practice ◽

Inflammatory Bowel

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P533 Adalimumab 80mg every other week in inflammatory bowel disease: Treatment intensification outcomes in real life clinical practice

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjab076.655 ◽

2021 ◽

Vol 15 (Supplement_1) ◽

pp. S507-S509

Author(s):

M I Calvo Moya ◽

I Omella Usieto ◽

I El Hajra Martinez ◽

E Santos Perez ◽

Y Gonzalez Lama ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Clinical Practice ◽

Bowel Disease ◽

Smoking Habit ◽

Real Life ◽

Fecal Calprotectin ◽

Treatment Intensification ◽

Loss Of Response ◽

Inflammatory Bowel

Abstract Background Adalimumab (ADA) intensification is recommended for inadequate or loss of response in inflammatory bowel disease (IBD) patients. A new presentation of ADA 80mg administered every other week (eow) has been approved as an alternative to ADA 40mg every week (ew). Data regarding impact of ADA 80mg eow in clinical practice is still scarce. The aim of this study was to assess long-term durability, safety and cost-effectiveness of treatment with ADA 80mg eow in patients with IBD. Methods A retrospective cohort study in a tertiary hospital that included all IBD patients under intensified maintenance therapy with ADA 80mg eow was performed. Durability was calculated considering the time from the first dose to treatment withdrawn or to the end of follow-up. Biological remission (BR) was defined as CR together with fecal calprotectin (FC) <250µg/g and C-reactive protein (CRP) <5mg/dl. Economic impact of ADA 80mg eow was estimated considering current price of both ADA 40mg and ADA 80mg pens at our centre. Results Sixty-three patients (52 CD and 11 CU) were included; median age 47 (IQR 39–59), 54% male; median duration of the disease before ADA of 11 years (IQR 6–20); 30% were active smokers. Among CD patients, 56% had ileal disease, 17% colonic and 27% ileocolonic. The inflammatory behavior was the most frequent (52%) and 31% had perianal disease. In UC, 55% had extensive colitis. 44 patients (70%) were bio-naïve and 36 (57%) received immunosuppressants at baseline. At the time of escalation, 48 patients (76%) were symptomatic. After intensification, 52 (83%) patients (CD 42 and UC 10) achieved CR and 46 (73%) BR. The changes in the levels of FC, CRP and ADA were significant (p <0.001) (Graphs 1–3). 22 patients (35%) discontinued treatment after a median of 6.5 (IQR 5–10) months due to: 11 no clinical response (50%), 4 loss of response (18%), 3 adverse events (14%) (psoriasis) and 4 endoscopic progression (18%). 44 patients (70%) remained under treatment and in CR (median follow-up 17 months, IQR 13–24) (Graph 4) and with a median ADA levels of 10.46 mg/l (IQR 7.34–15.25). Use of ADA 80 eow regimen saved 223500€ in patients who maintained treatment. In the multivariate analysis, being in CR when intensifying reduced the risk of treatment discontinuation by 87% (HR 0.13, 95%CI 0.02–0.99; p<0.001), having reached BR by 99.5% (HR 0.05, 95%CI 0.02–0.14; p <0.001) and having ADA levels ≥5 mg/l after intensification by 68% (HR 0.32, 95%CI 0.13–0.75; p = 0.02). Smoking habit was associated with treatment withdrawn (HR 1.74, 95%CI 1.02–2.96; p=0.04). Conclusion ADA intensification to 80mg eow in IBD patients is safe, effective and may reduce costs in real life clinical practice. Early intensification, even in CR, may enhance ADA treatment durability.

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A comparison of diagnostic performance between two quantitative rapid fecal calprotectin assays in detecting active inflammatory bowel disease

PLoS ONE ◽

10.1371/journal.pone.0255974 ◽

2021 ◽

Vol 16 (8) ◽

pp. e0255974

Author(s):

Jong-Mi Lee ◽

Joo Hee Jang ◽

Ji Hyeong Ryu ◽

Jaeeun Yoo ◽

Bo-In Lee ◽

...

Keyword(s):

Ulcerative Colitis ◽

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Diagnostic Performance ◽

Area Under The Curve ◽

Fecal Calprotectin ◽

Test Results ◽

Rapid Assays ◽

Endoscopic Score ◽

Inflammatory Bowel

Background Fecal calprotectin (FC) is widely used for the diagnosis and monitoring disease activity of inflammatory bowel disease (IBD). Quantitative rapid assays can be a reliable alternative to the time-consuming assay. This study aimed to evaluate and compare the diagnostic performance of two quantitative rapid FC assays (Ichroma calprotectin, and Buhlmann Quantum blue). Methods A total of 192 patients were included in this study; 84 patients with IBD (67 ulcerative colitis and 17 Crohn’s disease) and 108 patients with non-IBD. We compared quantitative FC levels in different disease statuses and evaluated the correlation between the FC results of the two FC kits. Diagnostic performances in predicting active IBD were evaluated in reference to different cut-off levels. Results The FC levels in 45 patients with active IBD as defined by endoscopic score were significantly higher compared to the inactive IBD and other diseases (P<0.05). Although the two assays’ results correlated (r = 0.642, P < 0.001), a significant deviation was observed (y (Buhlmannn) = -45.2 +8.9X (Ichroma)). The Diagnostic performances in predicting active IBD were comparable as area under the curve (AUC), 0.812, cut-off, 50, sensitivity, 64.4%, and specificity, 85.0% for iChroma assay and AUC, 0.826, cut-off, 100, sensitivity, 84.4%, and specificity 61.9% for Buhlmann Quantum Blue assay. FC levels using a cut-off of > 250 μg/g confirmed 85.7% (iChroma) and 64.1% (Buhlmann) of active IBD patients. Conclusion The results of the two rapid FC assays iChroma and Buhlmann showed a significant correlation, but the two test results were not interchangeable. With optimized cut-off values, rapid FC tests could be helpful in the diagnosis of IBD and differentiating active IBD from inactive or organic bowel disease.

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Leucine-rich alpha-2 glycoprotein as a marker of mucosal healing in inflammatory bowel disease

Scientific Reports ◽

10.1038/s41598-021-90441-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Eriko Yasutomi ◽

Toshihiro Inokuchi ◽

Sakiko Hiraoka ◽

Kensuke Takei ◽

Shoko Igawa ◽

...

Keyword(s):

Ulcerative Colitis ◽

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Fecal Calprotectin ◽

Mucosal Healing ◽

C Reactive Protein ◽

Reactive Protein ◽

Immunochemical Test ◽

Fecal Markers ◽

Inflammatory Bowel

AbstractLeucine-rich alpha-2 glycoprotein (LRG) may be a novel serum biomarker for patients with inflammatory bowel disease. The association of LRG with the endoscopic activity and predictability of mucosal healing (MH) was determined and compared with those of C-reactive protein (CRP) and fecal markers (fecal immunochemical test [FIT] and fecal calprotectin [Fcal]) in 166 ulcerative colitis (UC) and 56 Crohn’s disease (CD) patients. In UC, LRG was correlated with the endoscopic activity and could predict MH, but the performance was not superior to that of fecal markers (areas under the curve [AUCs] for predicting MH: LRG: 0.61, CRP: 0.59, FIT: 0.75, and Fcal: 0.72). In CD, the performance of LRG was equivalent to that of CRP and Fcal (AUCs for predicting MH: LRG: 0.82, CRP: 0.82, FIT: 0.70, and Fcal: 0.88). LRG was able to discriminate patients with MH from those with endoscopic activity among UC and CD patients with normal CRP levels. LRG was associated with endoscopic activity and could predict MH in both UC and CD patients. It may be particularly useful in CD.

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