dr. mahmoud mosli md frcpc abim msc...
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Biomarkers in Inflammatory Bowel Disease DR. MAHMOUD MOSLI
MD FRCPC ABIM MSC (CLINICAL EPIDEMIOLOGY AND BIOSTATISTICS)
ASSISTANT PROFESSOR, K ING ABDULAZIZ UNIVERSITY
Introduction
• The diagnosis of Inflammatory Bowel Disease (IBD) is often delayed
• Endoscopic disease activity does not correlate well with symptoms of IBD, especially Crohn’s disease (CD)
•Non-invasive biomarkers such as C-reactive protein (CRP), fecal calprotectin (CD) and stool lactoferrin (SL) might aid in diagnosing and monitoring patients with IBD
Endoscopy • Endoscopy (ileocolonoscopy) is the gold standard for diagnosing
and assessing response to therapy in IBD
• Cost, availability, wait time, and risk of perforation limit routine endoscopic evaluations in clinical practice
• Surrogate biomarkers are desirable
Surrogates for Bowel Inflammation • CRP: non - parametric distribution, large variances, non-production
• FC, SL: differential expression by disease and anatomical location
• Imaging: not ideal due to cost, time, availability, Ionizing radiation
for CT, operator dependence for US, however MRE is probably most promising
• Diagnosing IBD i.e. differentiating IBD from IBS
• Evaluating disease activity in IBD patients
• Predicting relapse in quiescent IBD patients
• Post operative surveillance in CD
• Monitoring response to therapy
FC and SL Applications
Cochrane Review: Biomarkers for Assessing Disease Activity in Inflammatory Bowel Disease Mosli M, Zou G, Garg SK, Feagan SG, MacDonald JK, Sandborn WJ, Chande N, Feagan BG
• Meta-analysis on the diagnostic accuracy of C-reactive protein (CRP), fecal calprotectin (FC), and stool lactoferrin (SL) for assessment of endoscopically defined disease activity in IBD
Methods
• Databases were searched from inception to November 6, 2014 for relevant cohort and case-control
• Studies that evaluated the diagnostic accuracy of CRP, FC, or SL and studies that used endoscopy as a gold standard in patients with symptoms consistent with active IBD.
• Sensitivities and specificities were pooled to generate operating property estimates for each test using a bivariate diagnostic meta-analysis.
5431 records identified
9 records from other sources
2515 records after duplicates removed
2515 records screened
2466 records excluded
29 full text articles assessed
10 records excluded with reasons
19 studies included in the qualitative synthesis
SENSITIVITY (95% CI)
Q = 51.71, df = 8.00, p = 0.00
I2 = 84.53 [75.54 - 93.52]
0.49[0.34 - 0.64]
0.70 [0.58 - 0.79]
0.62 [0.44 - 0.78]
0.52 [0.32 - 0.71]
0.24 [0.12 - 0.41]
0.07 [0.01 - 0.24]
0.47 [0.23 - 0.72]
0.60 [0.42 - 0.76]
0.48 [0.29 - 0.68]
0.67 [0.55 - 0.78]0.67 [0.55 - 0.78]
StudyId
COMBINED
Filik, 2006
Langhorst 2008
Langhorst 2008
Masoodi 2009
Inoue 2014
Inoue 2014
Langhorst 2008
Langhorst 2008
Karoui 2011
0.0 0.8
SENSITIVITY
SPECIFICITY (95% CI)
Q = 36.96, df = 8.00, p = 0.00
I2 = 78.35 [64.61 - 92.10]
0.92[0.72 - 0.98]
0.64 [0.46 - 0.79]
0.50 [0.16 - 0.84]
0.87 [0.60 - 0.98]
1.00 [0.91 - 1.00]
1.00 [0.72 - 1.00]
0.87 [0.60 - 0.98]
0.63 [0.24 - 0.91]
0.93 [0.66 - 1.00]
0.97 [0.85 - 1.00]0.97 [0.85 - 1.00]
StudyId
COMBINED
Filik, 2006
Langhorst 2008
Langhorst 2008
Masoodi 2009
Inoue 2014
Inoue 2014
Langhorst 2008
Langhorst 2008
Karoui 2011
0.2 1.0
SPECIFICITY
Mosli, M.H., et al., C-Reactive Protein, Fecal Calprotectin, and Stool Lactoferrin for Detection of Endoscopic Activity in Symptomatic Inflammatory Bowel Disease Patients: A Systematic Review and Meta-Analysis. Am J Gastroenterol, 2015. 110(6): p. 802-19; quiz 820.
Mosli, M.H., et al., C-Reactive Protein, Fecal Calprotectin, and Stool Lactoferrin for Detection of Endoscopic Activity in Symptomatic Inflammatory Bowel Disease Patients: A Systematic Review and Meta-Analysis. Am J Gastroenterol, 2015. 110(6): p. 802-19; quiz 820.
FC SL
Mosli, M.H., et al., C-Reactive Protein, Fecal Calprotectin, and Stool Lactoferrin for Detection of Endoscopic Activity in Symptomatic Inflammatory Bowel Disease Patients: A Systematic Review and Meta-Analysis. Am J Gastroenterol, 2015. 110(6): p. 802-19; quiz 820.
CRP
Cohen-Lyons D, Hadjinicolaou AV, Mosli MH, Garg SK, Khanna R, Zou G, Parker CE, Feagan BG, Jairath V, Levesque BG
Cochrane Review: Biomarkers for Evaluating Endoscopic Disease Activity in Asymptomatic Inflammatory Bowel Disease Patients
• Meta-analysis on the diagnostic accuracy of C-reactive protein (CRP), fecal calprotectin (FC), and stool lactoferrin (SL) for predicting endoscopically proven relapse in asymptomatic IBD patients
Methods
•Databases were searched from inception to December 18, 2015 for relevant cohort and case-control
• Studies that evaluated the diagnostic accuracy of CRP, FC, or SL, and used endoscopy as a gold standard to document future relapse, in patients with asymptomatic IBD.
• Sensitivities and specificities were pooled to generate operating property estimates for each test using a bivariate diagnostic meta-analysis.
5431 records identified
9 records from other sources
2515 records screened
2466 records excluded
29 full text articles assessed
10 records excluded with reasons
19 studies included in the qualitative synthesis
2515 records after duplicates removed
sensitivity specificity
Conclusions
• CRP, FC, and SL can accurately identify symptomatic IBD patients that have endoscopically active disease
• FC is less accurate when used to predict relapse in asymptomatic IBD patients
Case 1 - Biomarkers
• 32 year old female
• Patchy Crohn’s colitis x 2 years
• Presenting symptoms:
o Bloody diarrhea 8-10 / day
o Abdominal pain
o Mouth ulcers
o Joint aches
o Weight loss 10 kg
• Initial response to prednisone
• Intolerance to azathioprine • adalimumab monitoring with clinical response • In clinical remission after 1 year
o 2 formed non-bloody bowel movements daily o No pain o Good appetite, stable weight
0
100
200
300
400
500
600
700
Diagnosis Year 1 Year 2
0
5
10
15
20
25
30
35
40
Diagnosis Year 1 Year 2
Fecal calprotectin (µg/g) CRP (mg/L)
One year after prednisone induction therapy
Case 1 - Biomarkers • Clinical remission on adalimumab 40 mg q2 weeks
• Slight rise in fecal calprotectin and serum CRP