Fecal calprotectin

1. Ms C. F. 32yo
• CD (2002): TI
– TI stricture: R hemicolectomy 2005
• post-operative recurrence
– poor adherence/ refractory to steroids/
budesonide, ASA, AZA
• clinical trial GM-CSF
– acute abdomen: CT peritonitis – subtotal
colectomy, end ileostomy 2008
– “I want to stab my colorectal surgeon”

2. Ms C. F. 32yo
• Bankstown IBD clinic:
– increasing abdo pain
• not cramping
– no obstructive symptoms, stoma working
– empties stoma bag a few times a day
– lack of energy, motivation, mood, can’t sleep,
poor QOL
• other Hx?

3. Ms C. F. 32yo
– O/E:
• aggressive/ untrusting
• abdomen: non-distended, scars, stoma active normal
• non-tender
• normal bowel sounds
– investigations:
• normal FBC, LFT
• normal CRP, ESR
• small bowel U/S: thickened TI

4. Ms C. F. 32yo
• options?:
– repeat CT/ CT enteroclysis
– ileoscopy
– DBE
– MRI enteroclysis
– other

5. Mr N. V. 71yo
• CD: Dx 2000
– TI
– low dose prednisone, AZA
– acute SBO (SAN)
• conservative management

6. Mr N. V. 71yo
• investigations:
– normal CRP
– SB series: 15cm narrowed distal TI
• Options:
– trial of steroids/ step up immunomodulator
– ileoscopy colonoscopy
– CT abdomen
– small bowel enema
– other

8. Calprotectin
• calcium and zinc binding protein
– anti-microbial function
– 60% soluble cytosol proteins of neutrophils
– marker of neutrophils activity/ turnover
– = MRP8, MRP14, cystic fibrosis-associated antigen,
calgranulin, and S100

9. Faecal calprotectin
• stable in faeces
– resistant to proteolytic degradation
– can be stored at room temp for 1 week
– spot samples as reliable as 24 h collections
– serology: quick, cheap, reliable, reproducible
• increased in colitis
– correlates with WBC scan
– only need 0.1g in a 5mL buffer solution for results
– non specific: cancers, NSAID use, infection

10. Faecal calprotectin
• inflammation:
– differentiate IBD vs IBS
• useful when combined with CRP as inflam biomarkers
• especially normal CRP or elevated CRP from alternative
source of inflammation
– non-invasive monitoring of disease activity
– predict / diagnose IBD relapse
– ?marker of mucosal healing

11. Correlates with Endoscopic Activity
• Prospective study:
– 77 CD patients referred for ileocolonoscopy
• 106 colonoscopies
• Crohn’s disease index of severity (CDEIS)
– faecal calprotectin and lactoferrin, serum CRP
– CDAI
Sipponen et al Inflamm Bowel Dis Vol Jan 2008

12. Results
• CDEIS correlated with
– Faecal calprotectin
r=0.729 (p<0.001)
– CRP r=0.553 (p<0.001)
• CDAI and CRP
– Poor sensitivity for
endoscopic disease
activity
Sipponen et al Inflamm Bowel Dis Vol Jan 2008

13. Predict endoscopically active disease
(CDEI ≥ 3)
Sipponen et al Inflamm Bowel Dis Vol Jan 2008

14. Results
Sipponen et al Inflamm Bowel Dis Vol Jan 2008

15. Location of CD
• higher in colonic than in ileal CD
• isolated TI CD: calprotectin failed to correlate
with CDEIS (r=0.316, P<0.151, ns)
Sipponen et al Inflamm Bowel Dis Vol Jan 2008

16. Schoepfer et al Inflamm Bowel Dis Vol Dec 2009

18. Calprotectin Predicts Relapse
• 163 patients (89 CD, 74 UC) in clinical
remission
– Patients with higher faecal calprotectin (>150
mcg/g) at baseline, were more likely to relapse
• sensitivity 69% specificity 69%, PPV 30%, NPV 92%
– Fecal calprotectin’s (>150 lg/g) sensitivity and
specificity to predict relapses in
• UC patients were 31% and 91%
• CD patients were 28% and 93%.
Gisbert et al Inflamm Bowel Dis Vol Aug 2009

19. IBD vs IBS
• Prospective study of 136 patients
– 36 CD, 28 UC, 30 IBS, 42 healthy controls
– Primary endpoint: accuracy of fecal markers, CRP, FBC,
IBD antibodies for discriminating IBD from IBS
• workup of abdominal pain, altered bowel habit,
and/or anorectal bleeding
• all with colonoscopy ileoscopy, biopsies
• diagnosis of IBS required exclusion of other
conditions
– fulfilled the Rome II criteria
Schoepfer et al Inflamm Bowel Dis Vol Jan 2008

20. IBD vs IBS
Schoepfer et al Inflamm Bowel Dis Vol Jan 2008

21. IBD vs IBS
Schoepfer et al Inflamm Bowel Dis Vol Jan 2008

22. CRP in detection of IBD
• Sensitivity of CRP for detection of IBD ranges
between 50% and 60% for UC and between
70% and 100% for CD
• Schoepfer et al overall accuracy of CRP 73% in
detecting IBD
– 52% UC and 73% CD

24. Progress
• Mr N. V. 71yo:
– calprotectin: 0
– colonoscopy – no ileocolitis
• Ms C. F. 32yo:
– initially refused ileoscopy
– calprotectin >60, building rapport, ileoscopy linear
deep ulcers, commenced AZA
– 19 Apr 2011: TGN 183 (increased dose)
– ?biologics

26. Concord Hospital experience so far
• Introduction of faecal calprotectin into IBD
clinics to assess
– Clinical benefits
– Economic benefits
– Patient preference and satisfaction through
feedback questionnaire comparing colonoscopy
and faecal calprotectin

27. Concord faecal calprotectin audit
• Consecutive prospective cases collected over 3
months
• 27 patients from IBD Clinic
– 18 male, 9 female
– Age 18 to 71

28. Faecal calprotectin scale
• ≤15µg/g Negative
• 15µg/g - 60µg/g Positive
• ≥60µg/g Positive

29. Potential benefits
• Prevent unnecessary colonoscopies
• Prevent prolonged steroid use
• Pick-up of earlier stage of relapse
• Change medical management by assessment
of disease activity
• Differentiating organic vs functional causes of
GI symptoms

30. Potential benefits
• Reduction of unnecessary colonoscopies
• Improve clinical outcomes by reduction in
delay in diagnosis and/or treatment
• Reduction of costs by decreased burden on
endoscopy lists

31. Savings on one colonoscopy
avoided
• Day only admission for elective colonoscopy
– Admission $AUS 303
– Colonoscopy $AUS 321.65 - 451.40
– Staff costs (2RN) $AUS 240
– Total $AUS 864.65 - 994.40
• Faecal calprotectin
– Per test $AUS 18 - 40
• Overall saving per patient
– Minimum $AUS 824.65
– Maximum $AUS 976.40

32. Potential benefits of faecal
calprotectin in Concord IBD clinic audit

33. 27 patients
30 samples sent
27 successful samples
2 defective strips
1 specimen not able to be processed
20 patients participated in feedback
questionnaire
3 refused
4 were not contactable on 3 phone call
follow-ups
Patient satisfaction questionnaire
feedback

34. Patient satisfaction questionnaire
feedback
• How satisfied are you about the overall
experience on your last colonoscopy
– Very satisfied 5 4/20(20%)
– Satisfied 4 6/20(30%)
– Neutral 3 6/20(30%)
– Dissatisfied 2 1/20(5%)
– Very dissatisfied 1 2/20(10%)

35. Patient satisfaction questionnaire
feedback
• How comfortable are you about the overall
experience on giving a stool sample in clinic
– Very comfortable 5 9/20(45%)
– Comfortable 4 5/20(25%)
– Neutral 3 5/20(25%)
– Uncomfortable 2 0/20(0%)
– Very uncomfortable 1 1/20(5%)

37. Are you comfortable to give a stool
sample in clinic?

38. Samples given from home vs clinic

39. Would you be happy to repeat the
tests?

40. If you had to repeat a test with the
same outcomes, which would it be?

41. Summary
• Cost benefits from unnecessary colonoscopy
– $AUS 15,668.35
• 70% vs 50% of patients rated a positive
experience from their stool test and colonoscopy
respectively
• 95% of patients willing to repeat stool testing vs
65% of patients willing to repeat colonoscopy
• 90% of patients would choose to repeat stool
testing over colonoscopy
• Limiting factor “It is difficult to go on demand!”

42. Conclusion
• Faecal calprotectin is a quick, cheap, reliable,
reproducible marker for inflammation
– Guides clinician on treatment changes within the
time frame of the clinic
– Reduction of costs
– Reduce delay of treatment from relapse
– Improves patients compliance to testing
• Invaluable test in adjunct to current markers
of inflammation in managing IBD patients