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Meta-Analysis
. 2017 Oct 1;171(10):984-991.
doi: 10.1001/jamapediatrics.2017.1736.

Use of Laboratory Markers in Addition to Symptoms for Diagnosis of Inflammatory Bowel Disease in Children: A Meta-analysis of Individual Patient Data

Gea A Holtman  1 , Yvonne Lisman-van Leeuwen  1 , Andrew S Day  2   3 , Ulrika L Fagerberg  4   5 , Paul Henderson  6   7 , Stevan T Leach  8 , Gøri Perminow  9 , David Mack  10 , Patrick F van Rheenen  11 , Els van de Vijver  12 , David C Wilson  6   7 , Johannes B Reitsma  13 , Marjolein Y Berger  1
Affiliations
Meta-Analysis

Use of Laboratory Markers in Addition to Symptoms for Diagnosis of Inflammatory Bowel Disease in Children: A Meta-analysis of Individual Patient Data

Gea A Holtman et al. JAMA Pediatr. .

Abstract

Importance: Blood markers and fecal calprotectin are used in the diagnostic workup for inflammatory bowel disease (IBD) in pediatric patients. Any added diagnostic value of these laboratory markers remains unclear.

Objective: To determine whether adding laboratory markers to evaluation of signs and symptoms improves accuracy when diagnosing pediatric IBD.

Data sources: A literature search of MEDLINE and EMBASE from inception through September 26, 2016. Studies were identified using indexing terms and free-text words related to child, target condition IBD, and diagnostic accuracy.

Study selection: Two reviewers independently selected studies evaluating the diagnostic accuracy of more than 1 blood marker or fecal calprotectin for IBD, confirmed by endoscopy and histopathology or clinical follow-up, in pediatric patients with chronic gastrointestinal symptoms. Studies that included healthy controls and/or patients with known IBD were excluded.

Data extraction and synthesis: Individual patient data from each eligible study were requested from the authors. In addition, 2 reviewers independently assessed quality with Quality Assessment of Diagnostic Accuracy Studies-2.

Mean outcomes and measures: Laboratory markers were added as a single test to a basic prediction model based on symptoms. Outcome measures were improvement of discrimination by adding markers as a single test and improvement of risk classification of pediatric patients by adding the best marker.

Results: Of the 16 eligible studies, authors of 8 studies (n = 1120 patients) provided their data sets. All blood markers and fecal calprotectin individually significantly improved the discrimination between pediatric patients with and those without IBD, when added to evaluation of symptoms. The best marker-fecal calprotectin-improved the area under the curve of symptoms by 0.26 (95% CI, 0.21-0.31). The second best marker-erythrocyte sedimentation rate-improved the area under the curve of symptoms by 0.16 (95% CI, 0.11-0.21). When fecal calprotectin was added to the model, the proportion of patients without IBD correctly classified as low risk of IBD increased from 33% to 91%. The proportion of patients with IBD incorrectly classified as low risk of IBD decreased from 16% to 9%. The proportion of the total number of patients assigned to the intermediate-risk category decreased from 55% to 6%.

Conclusions and relevance: In a hospital setting, fecal calprotectin added the most diagnostic value to symptoms compared with blood markers. Adding fecal calprotectin to the diagnostic workup of pediatric patients with symptoms suggestive of IBD considerably decreased the number of patients in the group in whom challenges in clinical decision making are most prevalent.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Day is a paid member of advisory boards for Janssen and Abbvie in New Zealand. Dr Fagerberg has received financial support from InDex Pharmaceuticals (consultancy), Tillotts Pharma (consultancy), and Otsuka Pharma Scandinavia (congress fee, travel and honoraria for lecture). Dr Perminow has received partial funding for a newly started study from Takeda Pharmaceuticals and is a member of the advisory board and has received honoraria for lectures from AbbVie Inc. Dr Mack is a member of advisory boards for AbbVie Inc and Janssen Pharmaceuticals and is an owner and holds shares in Biotagenics. Dr van Rheenen receives research support from Bühlmann Laboratories for ongoing studies. Professor Wilson has received financial support from AbbVie (lecture fees, consultancy, meeting expenses), Falk Pharma GmbH (lecture fee), and Takeda Pharmaceuticals (consultancy). No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Pooled Area Under the Curve (AUC)
CRP indicates C-reactive protein; ESR, erythrocyte sedimentation rate; FCal, fecal calprotectin; and Hb, hemoglobin.
Figure 2.
Figure 2.. Pooled Improvement in Area Under the Curve (AUC) When Adding Markers to the Basic Model
A Δ AUC value greater than 0 implies an added discriminative value of the laboratory test, and a value of 0 or less implies no added discriminative value. CRP indicates C-reactive protein; ESR, erythrocyte sedimentation rate; FCal, fecal calprotectin; and Hb, hemoglobin.
See this image and copyright information in PMC

References

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