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Su1292 Biomarker Panel for Prediction of Mucosal Healing in Patients With Crohn's Disease Under Infliximab Therapy
AGA Abstracts
Su1293 Diagnosis of Iron Deficiency in Inflammatory Bowel Diseases by Transferrin Receptor-Ferritin Index Vered Abitbol, Anouk Esch, Didier Borderie, Vanessa Polin, Tessa Tabouret, Marion Dhooge, Geraldine Perkins, Fanny Maksimovic, Stanislas Chaussade Background Iron deficiency (ID) is common in patients with inflammatory bowel disease (IBD) but can be difficult to diagnose in the presence of inflammation. Serum ferritin level < 30 ng/mL is a diagnostic criterion of ID. Guidelines in IBD[1] consider ferritin level between 30-100 ng/mL associated with inflammation as criteria for ID diagnostic. The sTransferrin receptor-ferritin index (TfR-F) has a high sensitivity for ID diagnosis in chronic diseases[2]. The aim of the study was to assess the added value of TfR-F index to diagnosis of ID in a prospective cohort of IBD patients. Methods All consecutive IBD patients seen in our hospital from February to July 2013 were asked to participate in the study. Exclusion criteria were iron supplementation in the 3 previous months or lack of patient consent. IBD activity was assessed on symptoms and markers of inflammation (CRP, endoscopy, calprotectin). All patients had serum dosages of hemoglobin, hsCRP (N<2.5 mg/L), ferritin (F), transferrin saturation, vitamin B9 and B12, LDH, haptoglobin. Soluble transferrin receptor (sTfR) was measured by Roche Tina-quant®. TfR-F index was calculated as the ratio sTfR / log10 F. ID was defined by F < 30 ng/mL or TfR-F index > 2 in the presence of inflammation; TfR-F index < 1 excluded ID. Results 75 patients aged 38 (18-78) years, 40 males, 51 Crohn's disease (CD) and 24 ulcerative colitis (UC) were included. 35 patients (47%) had active disease. 25 patients (33%) had anemia (WHO criteria), including 14 CD and 11 UC. 4 patients (5%) had vitamin B12 deficiency and 4 (5%) vitamin B9 deficiency. No one had hemolysis. Mean F level was 76 (9-291) ng/mL and sTfR, 3.9 (1.6-12.8) mg/ L. 21 patients (28%) had F < 30 ng/mL, 31 (41%) F between 30-100 ng/mL and 23 (31%) F > 100 ng/mL. 14 patients (19%) had F between 30-100 ng/mL and CRP > 2.5 mg/L: 1 had vitamin B12 deficiency excluding TfR-F analysis, 6/13 patients (46%) had TfR-F > 2. 1/12 (8.3%) patients with F > 100 ng/mL and CRP > 2.5 mg/L had TfR-F > 2. Overall, ID was diagnosed in 28/75 patients (37.3%), in which 28% on the basis of F < 30 ng/mL and 9.3% with TfR-F index > 2 in the presence of inflammation. Conclusions This prospective study in IBD shows that TfR-F index in addition to serum ferritin < 30 ng/mL criterion increases by 9.3 % diagnosis rates of ID. Only 46% of the patients with ferritin between 30-100 ng/mL and inflammation have ID, suggesting that guidelines [1] overestimate ID in IBD. TfR-F index seems useful to the diagnosis of ID in IBD and prevents from overtreating by iron supplementation. References [1] Gasche C et al. Guidelines on the diagnosis and management of iron deficiency and anemia in Inflammatory Bowel Diseases. Inflamm Bowel Dis 2007;13:1545-1553 [2] Weiss G et al. Anemia of Chronic Disease. N Engl J Med 2005;352:1011-23
Su1292 Biomarker Panel for Prediction of Mucosal Healing in Patients With Crohn's Disease Under Infliximab Therapy Magali de Bruyn, Talat Bessissow, Thomas Billiet, Isabelle Cleynen, Richard Kirkland, Xinjun Liu, Scott Hauenstein, Katherine Drake, Sharat Singh, Marc Ferrante, Paul J. Rutgeerts, Gert A. Van Assche, Ingrid Arijs, Ghislain Opdenakker, Severine Vermeire Introduction. Infliximab has led to new therapeutic goals in Crohn's disease (CD) such as complete mucosal healing and improvement of quality of life. The current standard for assessing mucosal healing is endoscopy. However, frequent assessments are costly and uncomfortable to the patient. Non-invasive, accurate surrogate serum markers would therefore be welcomed to aid clinicians in predicting mucosal healing. Methods. In a retrospective study, 119 CD patients who started infliximab and who underwent serial endoscopies (before and during infliximab) were included. Serum samples were available at the time of endoscopy and levels of markers were correlated with the degree of healing (not healed, marked improvement or complete healing). Thirty-five biomarkers were measured in 181 serum samples with the use of CEER, a proprietary highly sensitive protein micro-array, or homogenous mobility shift assays (Prometheus Laboratories Inc., San Diego, CA). These markers included growth and repair factors, pro -and anti-inflammatory markers and the IBD SGI serology panel. Infliximab and antibodies to infliximab were also measured. Clinical information regarding age at sampling, gender, age at diagnosis, location of disease, anal involvement and previous surgery was included. For statistical analysis SPSS and R were used. Results. From the 119 CD patients, 64 CD patients showed complete healing with no relapse, whereas 55 CD patients never showed mucosal healing. Univariate analyses indicated that age and 12 serum markers (HGF, BTC, TWEAK, CRP, ICAM, SAA, VCAM, IL-2, IL-8, IFN-γ, IL-6 and IL-10) were significantly associated with mucosal healing (p<0.1). Selection of the best subset of predictors through multiple logistic regression analysis retained age [Odds ratio 0.97 (95% confidence interval 0.94-0.99), p=0.010], HGF [0.86 (0.79-0.94), p=0.001], BTC [1.24 (1.07-1.43), p=0.003], TWEAK [1.04 (1.01-1.07), p=0.014] and VCAM [0.93 (0.870.98), p=0.012] as independent predictors based on Bayesian information criterion and the results remained significant after bootstrapping. A cumulative prediction score was developed by combining the 5 prediction factors (Age<29.5 years, HGF<11.42 CU/ml, BTC>11.44 CU/ml, TWEAK>20.62 CU/ml and VCAM<4200 μg/ml) which resulted in a significant and gradual increased prediction of mucosal healing (Figure 1, linear-by-linear p<0.001). Conclusion. We have identified 1 clinical parameter and 4 serum markers as independent predictors of mucosal healing. All serum markers play a role in the pathogenic mechanisms of CD. HGF has a central role in angiogenesis and tissue regeneration, BTC is a member of the EGF family of growth factors, TWEAK is a cytokine that has overlapping signaling functions with TNF and VCAM is a cell-adhesion molecule. The combined biomarker panel could facilitate prediction of mucosal healing in the future.
AGA Abstracts
Su1294 Computed Tomography Enterography Versus Magnetic Resonance Enterography for Assessment of Disease Activity and Complications in Small Bowel Crohn's Disease: A Meta-Analysis of Head-to-Head Comparative Studies Yun Qiu, Ren Mao, Bai-li Chen, Yao He, Zhirong Zeng, Minhu Chen Background: Magnetic resonance enterography (MRE), a radiation-free technique, has been proposed as an alternative method to computed tomography enterography (CTE). Some studies have directly compared CTE and MRE in patients with small bowel Crohn's disease (CD) with variable results. This meta-analysis aimed to compare the overall diagnostic accuracy in assessing the activity of small bowel and complications. Methods: MEDLINE, EMBASE, CINAHL, and Cochrane databases were searched for studies on the accuracy of MRE and CTE, as compared with a predefined reference standard. Pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were calculated on a per-patient basis, the weighted area under the curve (AUC) was also evaluated. Results: A total of 290 small bowel CD patients from six different studies were analyzed. The pooled sensitivity and specificity of MRE to detect active small bowel CD was 87.9 % (95% confidence interval [CI]: 81.8-92.5) and 81.2% (95% CI: 71.9 -88.4), respectively. The area under the summary receiver-operating characteristic (sROC) curve (AUC) of MRE was 0.905(95% CI: 75.3 - 90.1). Likewise, the pooled sensitivity and specificity of CTE to predict active small bowel CD was 85.8% (95% CI: 79.2 - 90.9 ) and 83.6% (95% CI: 75.3 - 90.1) with the AUC of 0.898. MRE has a high sensitivity and specificity for predicting complication of active CD, which was slightly inferior for detecting fistula, stenosis, but superior in detecting abscess when compared with CTE. The pooled sensitivity of MRE to detect fistula, stenosis and abscess was 69.9%, 65.3% and 90.5%, respectively, compared to 81.0%, 74.4% and 84.2% for CTE. The pooled specificity of MRE to detect fistula, stenosis and abscess was 94.5%, 94.4% and 98.4%, respectively, compared to 95.3%, 94.8% and 92.8% for CTE. The AUC of MRE in detecting fistula, stenosis and abscess was
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Su1293 Diagnosis of Iron Deficiency in Inflammatory Bowel Diseases by Transferrin Receptor-Ferritin Index Vered Abitbol, Anouk Esch, Didier Borderie, Vanessa Polin, Tessa Tabouret, Marion Dhooge, Geraldine Perkins, Fanny Maksimovic, Stanislas Chaussade Background Iron deficiency (ID) is common in patients with inflammatory bowel disease (IBD) but can be difficult to diagnose in the presence of inflammation. Serum ferritin level < 30 ng/mL is a diagnostic criterion of ID. Guidelines in IBD[1] consider ferritin level between 30-100 ng/mL associated with inflammation as criteria for ID diagnostic. The sTransferrin receptor-ferritin index (TfR-F) has a high sensitivity for ID diagnosis in chronic diseases[2]. The aim of the study was to assess the added value of TfR-F index to diagnosis of ID in a prospective cohort of IBD patients. Methods All consecutive IBD patients seen in our hospital from February to July 2013 were asked to participate in the study. Exclusion criteria were iron supplementation in the 3 previous months or lack of patient consent. IBD activity was assessed on symptoms and markers of inflammation (CRP, endoscopy, calprotectin). All patients had serum dosages of hemoglobin, hsCRP (N<2.5 mg/L), ferritin (F), transferrin saturation, vitamin B9 and B12, LDH, haptoglobin. Soluble transferrin receptor (sTfR) was measured by Roche Tina-quant®. TfR-F index was calculated as the ratio sTfR / log10 F. ID was defined by F < 30 ng/mL or TfR-F index > 2 in the presence of inflammation; TfR-F index < 1 excluded ID. Results 75 patients aged 38 (18-78) years, 40 males, 51 Crohn's disease (CD) and 24 ulcerative colitis (UC) were included. 35 patients (47%) had active disease. 25 patients (33%) had anemia (WHO criteria), including 14 CD and 11 UC. 4 patients (5%) had vitamin B12 deficiency and 4 (5%) vitamin B9 deficiency. No one had hemolysis. Mean F level was 76 (9-291) ng/mL and sTfR, 3.9 (1.6-12.8) mg/ L. 21 patients (28%) had F < 30 ng/mL, 31 (41%) F between 30-100 ng/mL and 23 (31%) F > 100 ng/mL. 14 patients (19%) had F between 30-100 ng/mL and CRP > 2.5 mg/L: 1 had vitamin B12 deficiency excluding TfR-F analysis, 6/13 patients (46%) had TfR-F > 2. 1/12 (8.3%) patients with F > 100 ng/mL and CRP > 2.5 mg/L had TfR-F > 2. Overall, ID was diagnosed in 28/75 patients (37.3%), in which 28% on the basis of F < 30 ng/mL and 9.3% with TfR-F index > 2 in the presence of inflammation. Conclusions This prospective study in IBD shows that TfR-F index in addition to serum ferritin < 30 ng/mL criterion increases by 9.3 % diagnosis rates of ID. Only 46% of the patients with ferritin between 30-100 ng/mL and inflammation have ID, suggesting that guidelines [1] overestimate ID in IBD. TfR-F index seems useful to the diagnosis of ID in IBD and prevents from overtreating by iron supplementation. References [1] Gasche C et al. Guidelines on the diagnosis and management of iron deficiency and anemia in Inflammatory Bowel Diseases. Inflamm Bowel Dis 2007;13:1545-1553 [2] Weiss G et al. Anemia of Chronic Disease. N Engl J Med 2005;352:1011-23
Su1292 Biomarker Panel for Prediction of Mucosal Healing in Patients With Crohn's Disease Under Infliximab Therapy Magali de Bruyn, Talat Bessissow, Thomas Billiet, Isabelle Cleynen, Richard Kirkland, Xinjun Liu, Scott Hauenstein, Katherine Drake, Sharat Singh, Marc Ferrante, Paul J. Rutgeerts, Gert A. Van Assche, Ingrid Arijs, Ghislain Opdenakker, Severine Vermeire Introduction. Infliximab has led to new therapeutic goals in Crohn's disease (CD) such as complete mucosal healing and improvement of quality of life. The current standard for assessing mucosal healing is endoscopy. However, frequent assessments are costly and uncomfortable to the patient. Non-invasive, accurate surrogate serum markers would therefore be welcomed to aid clinicians in predicting mucosal healing. Methods. In a retrospective study, 119 CD patients who started infliximab and who underwent serial endoscopies (before and during infliximab) were included. Serum samples were available at the time of endoscopy and levels of markers were correlated with the degree of healing (not healed, marked improvement or complete healing). Thirty-five biomarkers were measured in 181 serum samples with the use of CEER, a proprietary highly sensitive protein micro-array, or homogenous mobility shift assays (Prometheus Laboratories Inc., San Diego, CA). These markers included growth and repair factors, pro -and anti-inflammatory markers and the IBD SGI serology panel. Infliximab and antibodies to infliximab were also measured. Clinical information regarding age at sampling, gender, age at diagnosis, location of disease, anal involvement and previous surgery was included. For statistical analysis SPSS and R were used. Results. From the 119 CD patients, 64 CD patients showed complete healing with no relapse, whereas 55 CD patients never showed mucosal healing. Univariate analyses indicated that age and 12 serum markers (HGF, BTC, TWEAK, CRP, ICAM, SAA, VCAM, IL-2, IL-8, IFN-γ, IL-6 and IL-10) were significantly associated with mucosal healing (p<0.1). Selection of the best subset of predictors through multiple logistic regression analysis retained age [Odds ratio 0.97 (95% confidence interval 0.94-0.99), p=0.010], HGF [0.86 (0.79-0.94), p=0.001], BTC [1.24 (1.07-1.43), p=0.003], TWEAK [1.04 (1.01-1.07), p=0.014] and VCAM [0.93 (0.870.98), p=0.012] as independent predictors based on Bayesian information criterion and the results remained significant after bootstrapping. A cumulative prediction score was developed by combining the 5 prediction factors (Age<29.5 years, HGF<11.42 CU/ml, BTC>11.44 CU/ml, TWEAK>20.62 CU/ml and VCAM<4200 μg/ml) which resulted in a significant and gradual increased prediction of mucosal healing (Figure 1, linear-by-linear p<0.001). Conclusion. We have identified 1 clinical parameter and 4 serum markers as independent predictors of mucosal healing. All serum markers play a role in the pathogenic mechanisms of CD. HGF has a central role in angiogenesis and tissue regeneration, BTC is a member of the EGF family of growth factors, TWEAK is a cytokine that has overlapping signaling functions with TNF and VCAM is a cell-adhesion molecule. The combined biomarker panel could facilitate prediction of mucosal healing in the future.
AGA Abstracts
Su1294 Computed Tomography Enterography Versus Magnetic Resonance Enterography for Assessment of Disease Activity and Complications in Small Bowel Crohn's Disease: A Meta-Analysis of Head-to-Head Comparative Studies Yun Qiu, Ren Mao, Bai-li Chen, Yao He, Zhirong Zeng, Minhu Chen Background: Magnetic resonance enterography (MRE), a radiation-free technique, has been proposed as an alternative method to computed tomography enterography (CTE). Some studies have directly compared CTE and MRE in patients with small bowel Crohn's disease (CD) with variable results. This meta-analysis aimed to compare the overall diagnostic accuracy in assessing the activity of small bowel and complications. Methods: MEDLINE, EMBASE, CINAHL, and Cochrane databases were searched for studies on the accuracy of MRE and CTE, as compared with a predefined reference standard. Pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were calculated on a per-patient basis, the weighted area under the curve (AUC) was also evaluated. Results: A total of 290 small bowel CD patients from six different studies were analyzed. The pooled sensitivity and specificity of MRE to detect active small bowel CD was 87.9 % (95% confidence interval [CI]: 81.8-92.5) and 81.2% (95% CI: 71.9 -88.4), respectively. The area under the summary receiver-operating characteristic (sROC) curve (AUC) of MRE was 0.905(95% CI: 75.3 - 90.1). Likewise, the pooled sensitivity and specificity of CTE to predict active small bowel CD was 85.8% (95% CI: 79.2 - 90.9 ) and 83.6% (95% CI: 75.3 - 90.1) with the AUC of 0.898. MRE has a high sensitivity and specificity for predicting complication of active CD, which was slightly inferior for detecting fistula, stenosis, but superior in detecting abscess when compared with CTE. The pooled sensitivity of MRE to detect fistula, stenosis and abscess was 69.9%, 65.3% and 90.5%, respectively, compared to 81.0%, 74.4% and 84.2% for CTE. The pooled specificity of MRE to detect fistula, stenosis and abscess was 94.5%, 94.4% and 98.4%, respectively, compared to 95.3%, 94.8% and 92.8% for CTE. The AUC of MRE in detecting fistula, stenosis and abscess was
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