Pre-endoscopy Point of Care Test (Simtomax®- IgA/IgG-Deamidated Gliadin Peptide) for Coeliac Disease in Iron Deficiency: Diagnostic Accuracy and a Cost-Saving Economic Model.
Lau MSY, Mooney PD, White W et al.
BMC Gastroenterology 2016, 16:115 DOI 10.1186/s12876-016-0521-5
The prevalence of coeliac disease (CD) is 1%, however, 75% of cases remain undiagnosed. One of the common presenting symptoms is anaemia, which affects 15-26.8% of untreated patients, and is usually as a result of iron, folate or B12 deficiency due to malabsorption. Iron-deficiency anaemia affects between 2-5% of the general population in the developed world.
BMC Gastroenterology 2016, 16:115 DOI 10.1186/s12876-016-0521-5
The prevalence of coeliac disease (CD) is 1%, however, 75% of cases remain undiagnosed. One of the common presenting symptoms is anaemia, which affects 15-26.8% of untreated patients, and is usually as a result of iron, folate or B12 deficiency due to malabsorption. Iron-deficiency anaemia affects between 2-5% of the general population in the developed world.
Screening individuals with anaemia offers one way to increase the detection of CD. Existing data has shown 2.6-8.7% of patients attending endoscopy with anaemia are subsequently diagnosed with CD. In addition, the current British Society of Gastroenterology (BSG) guidelines on iron-deficiency anaemia recommend routine screening for CD with tissue transglutaminase (TTG) and/or endomysial antibodies (EMA). However, availability and utilisation of coeliac serology prior to endoscopy appears to be variable. If serology is unavailable, this commits the clinician to take duodenal biopsies; an expensive way of detecting cases.
The aim of this study was to evaluate the role of utilising a pre-endoscopy Point of Care Test (POCT) for CD in iron-deficiency in a cost-saving model. Adherence to the BSG guidelines for coeliac serological screening in iron-deficiency anaemia was initially assessed to determine the availability of pre-endoscopy serology in real clinical practice. The sensitivity of the Simtomax POCT in detecting CD in iron deficiency was then ascertained and the economic impact of using a pre-endoscopy DGP-based POCT to target biopsy taking only in those with a positive test result assessed. Alternative causes for the iron-deficiency, other than CD, that could be found from duodenal histology, were also explored. This was to evaluate whether this approach would miss other duodenal pathologies causing anaemia.
This study involved three groups:
In this study, the prevalence of CD in iron deficiency was found to be 1.3-19.5%. In group 1, a total of 934 patients with anaemia underwent a gastroscopy with duodenal biopsy. Coeliac serology was available in 33.8% of patients prior to endoscopy; 14% of serology samples were undertaken in primary care. In group 2, 19.5% of 133 patients were diagnosed with CD. Simtomax correctly identified all cases of CD with a positive serology (IgA EMA/IgA TTG) and Marsh grade 3a-c villous atrophy. The sensitivity, specificity, positive and negative predictive PPV and NPV) values of Simtomax IgA TTG were 100%, 82.2%, 57.8% and 100% vs 96.2%, 91.5%, 73.5% and 99% respectively. The duodenal histology review did not identify any causes other than CD for the iron deficiency. With a 100% NPV, a biopsy following a negative Simtomax test would be highly unlikely to yield any diagnosis for iron deficiency in routine clinical practice and therefore could be avoided in patients with iron deficiency with or without anaemia.
Economic Model
In the group 2 cohort, 88 out of 133 patients (66.2%) had a negative Simtomax test result. Due to the 100% sensitivity and negative predictive value of Simtomax in this cohort, a duodenal biopsy could have been safely avoided in these patients. After taking into account the cost of using Simtomax on all patients, the overall cost saving in this cohort would be £4908. This equates to a potential cost saving of £3690 per 100 gastroscopies (all figures based on costings at the Royal Hallamshire Hospital in Sheffield).
In conclusion, this study demonstrated that in clinical practice the availability of coeliac serology in anaemia prior to gastroscopy was low (33.8%). The study also found the Simtomax test had a superior sensitivity and negative predictive value compared with standard serology. These results are similar to other published findings on the performance of the POCT, Simtomax, compared with standard serology. Therefore, Simtomax offers an effective and cost-saving screening test for CD in iron deficiency in the endoscopy setting through avoidance of unnecessary duodenal biopsies in patients with a negative test result.
The aim of this study was to evaluate the role of utilising a pre-endoscopy Point of Care Test (POCT) for CD in iron-deficiency in a cost-saving model. Adherence to the BSG guidelines for coeliac serological screening in iron-deficiency anaemia was initially assessed to determine the availability of pre-endoscopy serology in real clinical practice. The sensitivity of the Simtomax POCT in detecting CD in iron deficiency was then ascertained and the economic impact of using a pre-endoscopy DGP-based POCT to target biopsy taking only in those with a positive test result assessed. Alternative causes for the iron-deficiency, other than CD, that could be found from duodenal histology, were also explored. This was to evaluate whether this approach would miss other duodenal pathologies causing anaemia.
This study involved three groups:
- Group 1 was a multicentre retrospective analysis of all patients (n=934) with anaemia attending a gastroscopy with duodenal biopsy at 4 UK hospitals (Addenbrooke’s, Bradford, Hull and Whipps Cross) over a 12 month period. The availability of coeliac serology prior to gastroscopy was reviewed.
- Group 2 was a non-inferiority prospective study comparing the sensitivities of Simtomax to conventional serology in an iron-deficient cohort. 133 consecutive patients were recruited with iron deficiency (with or without anaemia) from a single CD research endoscopy list in Sheffield. All patients undertook conventional and Simtomax serology (IgA EMA, IgA TTG, total IgA) at the point of endoscopy and the results were compared against their duodenal histology. Patients with known CD or those on a gluten-free diet (GFD) were excluded. The endoscopist had clinical information of the patients but was blinded to the results of the POCT.
- Group 3 was a retrospective histological analysis of 153 patients attending a separate non-coeliac specific iron-deficiency anaemia clinic at another hospital. Duodenal histology of the patients was reviewed to determine any alternative causes for their anaemia, other than CD.
In this study, the prevalence of CD in iron deficiency was found to be 1.3-19.5%. In group 1, a total of 934 patients with anaemia underwent a gastroscopy with duodenal biopsy. Coeliac serology was available in 33.8% of patients prior to endoscopy; 14% of serology samples were undertaken in primary care. In group 2, 19.5% of 133 patients were diagnosed with CD. Simtomax correctly identified all cases of CD with a positive serology (IgA EMA/IgA TTG) and Marsh grade 3a-c villous atrophy. The sensitivity, specificity, positive and negative predictive PPV and NPV) values of Simtomax IgA TTG were 100%, 82.2%, 57.8% and 100% vs 96.2%, 91.5%, 73.5% and 99% respectively. The duodenal histology review did not identify any causes other than CD for the iron deficiency. With a 100% NPV, a biopsy following a negative Simtomax test would be highly unlikely to yield any diagnosis for iron deficiency in routine clinical practice and therefore could be avoided in patients with iron deficiency with or without anaemia.
Economic Model
In the group 2 cohort, 88 out of 133 patients (66.2%) had a negative Simtomax test result. Due to the 100% sensitivity and negative predictive value of Simtomax in this cohort, a duodenal biopsy could have been safely avoided in these patients. After taking into account the cost of using Simtomax on all patients, the overall cost saving in this cohort would be £4908. This equates to a potential cost saving of £3690 per 100 gastroscopies (all figures based on costings at the Royal Hallamshire Hospital in Sheffield).
In conclusion, this study demonstrated that in clinical practice the availability of coeliac serology in anaemia prior to gastroscopy was low (33.8%). The study also found the Simtomax test had a superior sensitivity and negative predictive value compared with standard serology. These results are similar to other published findings on the performance of the POCT, Simtomax, compared with standard serology. Therefore, Simtomax offers an effective and cost-saving screening test for CD in iron deficiency in the endoscopy setting through avoidance of unnecessary duodenal biopsies in patients with a negative test result.
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