Improving test usage by education and vetting by dzN2lf9

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									       Faecal Calprotectin:
 New test for bowel inflammation
Claudia Tomkins
Coventry and Warwickshire Pathology Services
Overview
• Why test for bowel inflammation?
• What is faecal calprotectin?
• Why is it useful?
• UHCW pilot results
• Current service provision
• Recommendations
• Summary
NICE (2008) for IBS in Primary Care
• Positive [exclusion] diagnosis of IBS if appropriate symptoms
• Refer to secondary care for further investigation people with
   possible IBS symptoms who have any of the following ‘red flag’
   indicators:
- Unintentional or unexplained weight loss
- Rectal bleeding
- Abdominal or rectal masses
- Anaemia
- Family history of bowel or ovarian cancer
- Change in bowel habit lasting more than 6 weeks in person aged
   over 50 yrs, with looser and/or more frequent stools
- Raised inflammatory markers for inflammatory bowel disease
NICE (2008) for IBS in Primary Care
• Inflammatory markers for inflammatory bowel disease
• CRP and ESR recommended in 2008
• Better marker now available

                        Sensitivity (%)   Specificity (%)

  CRP and ESR                    35                73
  Faecal calprotectin            90                80
What is calprotectin?
• Calcium-binding S100A8/S100A9 heterodimer highly
  abundant in the cytoplasm of neutrophils
• Upon neutrophil activation, calprotectin is released and
  may be detected in body fluids
• Calprotectin is stable in faeces for up to five days, and
  measurement in a single sample correlates well with
  established markers of intestinal inflammation and
  permeability (4-day faecal collection of 111In labelled
  white cells, 51Cr-EDTA excretion, and lactulose/L-
  rhamnose ratio).
Why faecal calprotectin?
• Faecal calprotectin (FC) measurement can help rule out
  organic disease among patients with IBS symptoms
• Single FC measurement included in the initial
  diagnostic work-up
• Faster diagnosis and cost-saving due to reduction in
  colonoscopies
• Pooled sensitivity 93% and specificity 96% (diagnostic
  meta-analysis)
Why faecal calprotectin?
• Non-invasive test
• Suitable for Primary Care
• Also useful for monitoring known IBD patients, and
  investigating symptom flares non-invasively
• More sensitive and specific than current inflammatory
  markers (ESR and CRP)
Calprotectin service
• Available in a few centres nationally


• UHCW evaluation project started September 2010
• Joint Gastro-Biochemistry led
• Funded by Biochemistry
Phase 1 participants
             Functional bowel disease    Organic bowel disease
N=                     35                            27
Mean age             38 years                    34 years
(range)              (20-49)                      (15-39)
Gender            Males n = 13                 Males n = 14
                 Females n = 22              Females n = 13
Endoscopic   No abnormality n = 35        IBD (UC/CD) n = 18
diagnoses                                      Proctitis n = 3
                                             Diverticulitis n = 2
                                          Inflammatory polyp n = 1
                                            Haemarrhoids n = 1
                                        Bile acid malabsorption n = 1
                                                                      10
      Immundiagnostik kit




                                                                      IBS
                                                                      9




                                                                      IBD in
                                                                      remission
                                                                      8




                                                                      Other organic
                                                                      7




                                                                      disease
                                                                      IBD
                                                                      6
                                                                      5
                                                                      IBS




                                                                      4
      Buhlmann kit




                                                                      IBD in




                                                                      3
                                                                      remission
                                                                      Other organic




                                                                      2
                                                                      disease
                                                                      IBD




                                                                      1




                                                                                  Results
                                                                      0
                                                                1.0
10000.0




                            1000.0




                                            100.0




                                                         10.0
                                     calprotectin ug/g
                     10000.0
                                          Buhlmann kit                               Immundiagnostik kit


                      1000.0
 calprotectin ug/g




                       100.0

                                                                                                                              50 ug/g


                        10.0




                         1.0
                               0    1             2          3         4   5    6            7           8         9     10
                                   IBD

                                         disease
                                         Other organic

                                                         remission
                                                         IBD in

                                                                     IBS




                                                                               IBD

                                                                                       disease
                                                                                       Other organic

                                                                                                       remission
                                                                                                       IBD in

                                                                                                                   IBS
Results
 Sensitivity and specificity

%                N=   Sensitivity   Specificity    Positive    Negative
(95% C.I.)                                        predictive   predictive
                                                    value        value
Raised CRP       33        40           91           67           78
or ESR                   (14-72)      (70-98)      (24-94)      (57-91)
Rome II          45        91           10           76           25
criteria                 (78-97)      (5-43)       (59-87)      (13-78)
Imm’ik cut off   28        78           95           88           90
50 ug/g                  (40-96)     (72-100)      (47-99)      (68-98)
Combined         48        85           86           69           94
data                    (54-97)      (69-95)       (41-89)      (79-99)


In diagnostic meta-analysis, the pooled results (adults):
sensitivity 0.93 (0.85-0.97)
specificity 0.96 (0.79-0.99)
Summary of Phase 1 results
• Although number of patients in this validation pilot are
  small, diagnostic performance with both kits are very
  similar to larger published studies
• Cut-off 50 ug/g preferred using Immundiagnostik kit
Cost analysis
• Using national tariff data, the following cost comparison was
  published by the Centre for Evidence Based Purchasing for a
  population of 1,000 patients:

               Correctly     Correctly     Total costs
               diagnosed     diagnosed
               IBS cases     IBD cases
Faecal         720           90            £312,143
Calprotectin
ESR + CRP      657           35            £325,606


• Reproduced from CEBP Economic report, 2010
• FC @ £25 per test
Impact on colonoscopies
• 250 colonoscopies per year at UHCW for acute/chronic
  diarrhoea or alternating bowel habit
• ~90% of these patients have a final Dx of IBS (local data
  93% and in correlation with national data 90%)
• Some of these patients may be diagnosed as IBS using
  FC and will not require colonoscopy
• Some patients will still require colonoscopy due to clinical
  or patient concern, despite low FC
• Some patients may have a “false positive” FC, but this
  may help in further investigations even if colonoscopy
  NAD
• Exact financial impact on colonoscopies will be
  determined by Phase 2
Recommendations
• Continue to Phase 2 pilot
• 6-12 months of Faecal Calprotectin service for Coventry
  and Warwickshire (and Birmingham)
• Available to Primary and Secondary care physicians
• Agreed protocols for testing and when to refer (GPs)
• Advice on appropriate action provided with report
• Reference range <50 ug/g
• Turn-around time 2 weeks
    Recommended Primary Care guidelines
                              Patient <45 years with symptoms of
   (change in bowel habit, abd pain, bloating) for the past 3 months and no red flag symptoms



 TTG positive,              Measure TTG + FBC, TSH and
 treat as coeliac           stool for calprotectin at same time
 disease.
                                                                     If TTG, FBC,
                                                                     TSH & FC - NAD
                             Follow anaemia           Measure faecal
                             pathway.                 calprotectin (£25          Likely IBS
                                                      per test)



FC <50 ug/g, no evidence of active bowel
inflammation. Symptoms highly likely to be due
to IBS. If diarrhoea persists, or there remains
clinical concern, consider referral for further              FC >50 ug/g, Raised calprotectin
investigations (e.g. bile acid malabsorption etc.)           consistent with active bowel
                                                             inflammation, [please refer to
                                                             Gastroenterology].
Recommended Secondary Care use of
Faecal Calprotectin
Consider measuring faecal calprotectin for...
• Patients <45 years ? IBS vs. organic disease
• Uncertain findings on endoscopy/histology
• Baseline measurement in IBD
• IBD follow up ?active ?remission (esp. if symptom flare)
Recommended use of Faecal Calprotectin
• Do NOT use FC for ?bowel cancer
• Do NOT use FC for ?infection

• DO give your patient a stool pot; a 2p sized amount of
  sample is sufficient (solid stool best if possible)
• DO ask them to bring it to their local hospital/GP to
  send to BIOCHEMISTRY (not microbiology) – stable at
  room temp
• DO fill in as much clinical info as you can, incl.
  symptoms and duration
Faecal calprotectin service
• FC is currently available at UHCW (phase 2 pilot)
• Funding agreed on principle for 1 year (external
  funding) but will be putting a case to Primary Care
  Commissioners in due course for follow-on funding
• Please contact Biochemistry or Gastro to discuss any
  particular patient or for more info about the test
• Claudia Tomkins 02476 965478
• Dr Ramesh Arasaradanam 02476 966087
Thanks to
• Dr Ramesh Arasaradanam
• Paula Bennet and admin staff at Endoscopy UH
• Gastro team
• Dr Steve Smith
• Biochemistry lab staff
• Patient volunteers
• BioHit and Alpha Labs (vendors of FC kits)

								
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