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Mo1667 Lactoferrin Level is an Indicator of Mucosal Healing in Patients With Ulcerative Colitis: A Prospective 12-Month Monitoring Study
AGA Abstracts
PDAI score was 2 (range 0-13) with 31 patients (11.3%) having pouchitis and 8 (2.9%) having inflammation of the afferent limb, based on the PDAI criteria. The median PAS was 8 (range: 0-20) with 45 patients (16.4%) having pouchitis and 12 (4.3%) having inflammation of the afferent limb, based on these criteria. The clinical components of both PDAI and PAS were found to highly correlate with the total scores, with CC's of 0.66 and 0.7 for the PDAI and PAS respectively. Poor correlations were found between the clinical and the endoscopic or histological parts of the indices with CC's of 0.18 and 0.07 for the clinical to endoscopic and acute histological findings respectively using the PDAI criteria and CC's of 0.2, 0.12 and 0.05 for clinical to endoscopic, acute histological and chronic histological findings respectively using the PAS criteria. Conclusions: There is poor correlation between clinical and endoscopic/histological scores in patients with IPAA. Clinical symptoms may not reflect endoscopic or histological evidence of inflammation. Further research is required to understand the relationship between the association of signs of pouch inflammation and clinical symptoms.
of other available biologic agents to achieve mucosal healing are necessary to validate our findings.
Mo1667 Lactoferrin Level is an Indicator of Mucosal Healing in Patients With Ulcerative Colitis: A Prospective 12-Month Monitoring Study Jost Langhorst, Andreas Rueffer, Marcus Baecker, Gustav J. Dobos, James H. Boone
Outcomes of a hypothetical cohort of 100,000 patients with moderate-to-severe Crohn's disease treated with infliximab
INTRODUCTION: Inflammatory bowel disease is challenging to manage and includes periods of disease activity and remission. Recent studies have identified a treatment goal of mucosal healing for optimal patient outcome and decrease in surgery. Fecal lactoferrin is a validated biomarker for intestinal inflammation and increased levels indicate active disease. AIMS & METHODS: In this study, we followed patients (pts) with inactive ulcerative colitis (CAI <5) for 12-months and evaluated C-reactive protein (CRP - cut-off: 0.5mg/dl), white blood cell count (WBC - cut-off: 8.5/nl), and fecal lactoferrin levels (FLA - cut-off: 7.25μg/g) as biomarkers for active disease and for determining mucosal healing. A total of 85 pts with inactive UC were evaluated at 6 different time-points (baseline, 1; 3; 6; 9; 12 month). Stool and serum specimens were collected for quantitative fecal lactoferrin by immunoassay and lab parameters (CRP and WBC), respectively. Sigmoidoscopy with histology was performed at baseline, in the event of an acute flare (CAI>4) or at the end of the 12 month period to determined the presence of mucosal inflammation. Endoscopy score was used for defining mucosal healing. In addition, absence of acute immune cell infiltration, crypt abscess, mucin depletion and breaches in the surface epithelium (Riley Score) was used for defining histological healing. RESULTS: There were 85 patients, male-female ratio 1:1 and age range 20 to 75 years that were monitored for the complete 12-months. A total of 36 pts suffered a flare and 49 pts experienced sustained remission using CAI. Median FLA levels were 40μg/ g vs 5μg/g (p<0.0001), median CRP levels 0.6mg/dl vs 0.1mg/dl (p<0.001) and median WBC levels 7.6 vs 6.0/nl (p=0.01) for flare vs remission, respectively. Of the pts in sustained remission, 44 achieved mucosal healing based on Endoscopy Score 0-1 (Rachmilewitz). Median levels (at 12 month) of pts with mucosal healing and pts with mucosal activity were 5μg/g vs 37μg/g for FLA (p=0.09), 0.2mg/dl vs 0.1mg/dl for CRP (p=0.882) and 5.9 vs 6.0/ nl for WBC (p=0.787), respectively. Of the pts in sustained remission, 41 did not show any signs of acute histological activity (Riley Score). Median levels (at 12 month) of pts without signs of acute histological activity and pts with signs of acute histological activity were 4.6μg/ g vs 14.4μg/g for FLA (p=0.198), 0.2mg/dl vs 0.1mg/dl for CRP (p=0.948) and 6.0 vs 6.0/ nl for WBC (p=0.759), respectively. FLA was the only biomarker to show a median level above cut-off for active disease defined by endoscopy as well as histology for pts in sustained clinical remission. CONCLUSION: Our results show that fecal lactoferrin is a useful biomarker for identifying active UC and for determining patients that achieve mucosal healing.
Mo1669 Correlation Between Serological Biomarkers and Clinical Activity in Patients With Inflammatory Bowel Disease (IBD) Pablo Miranda-García, Maria Chaparro, Javier P. Gisbert Background: Biomarkers are used routinely to monitor activity in patients with IBD. However, the correlation between these markers and clinical disease activity is not well established. Objectives: To evaluate the correlation between several serological biomarkers and clinical activity in patients with IBD. To identify the serological biomarkers with the best accuracy to assess the clinical activity in patients with IBD. Methods: Patients followed-up at the IBD Unit from our hospital were prospectively included. A blood sample was obtained from each patient and haematological parameters and several biomarkers were determined: Creactive protein (CRP), orosomucoid, erythrocyte sedimentation rate (ESR), ferritin, and fibrinogen. The clinical activity was assessed by the Partial Mayo Score in the case of ulcerative colitis (UC) and by the Harvey-Bradshaw activity index in Crohn's disease (CD) patients. The accuracy of each biomarker was assessed by the area under the ROC curve (AUC). The best cut-off value for each biomarker was identified; for it, sensitivity (Se), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV) were calculated. Results: Three-hundred and fifty patients were included. The median age was 46 years and the median time of evolution of the disease was 3 years, 52% were female and 59% had CD. The overall accuracy and the accuracy for CD and UC of the best serological biomarkers are shown in the tables. Conclusions: The correlation between commonly used serological biomarkers and the clinical activity of IBD is low. The accuracy of these markers is, in general, worse in UC than in CD. CRP, fibrinogen and haemoglobin have the best correlation with the clinical activity in CD. Overall accuracy (CD and UC)
Mo1668 Mucosal Healing is a Cost-Effective Endpoint With Biologic Therapy in Crohns Disease − Results From a Decision Analysis Ashwin N. Ananthakrishnan, Joshua R. Korzenik, Chin Hur Introduction: Observational studies have demonstrated that mucosal healing may be associated with reduction in the need for hospitalizations or surgeries for moderate to severe Crohn's disease (CD). Infliximab (IFX) has demonstrated that it is possible to achieve and maintain endoscopic healing in CD. Whether treatment to achieve mucosal healing is a costeffective endpoint has not been established previously. Methods: We constructed a decision analytic model comparing two treatment strategies for patients with moderate-to-severe CD initiating treatment with IFX. In the clinical response (CR) arm, patients without clinical response or remission at year 1 are dose escalated. In the mucosal healing (MH) arm, patients with persistence of mucosal ulceration at year 1 undergo treatment escalation irrespective of clinical symptoms. Patients were modeled to remain at risk for hospitalization and surgeries while they have active disease. The model encompassed a 2 year time horizon. Results: In the base case, the MH strategy was more effective at 2 years (QALY 0.71) compared to the CR strategy (QALY 0.69) but was also more expensive with an estimated cost of $58,386 compared to the CR strategy ($57,195) for an ICER of $47,502/QALY gained. Our results were sensitive to the ability of existing biologic therapies to achieve clinical response as well as endoscopic healing. For clinical response rates of < 48% at year 1, the MH strategy was the dominant (both more effective and less costly) strategy. For the CR arm to be dominant required a clinical response rate > 72%. For clinical response rates > 57%, the ICER associated with MH was above the willingness-to-pay threshold. Conversely, if the likelihood of mucosal healing at 1 year was > 54%, the MH strategy was dominant. Alternatively expressed, for ratios of mucosal healing to clinical response of 0.84 or higher, the MH strategy was costeffective. In a hypothetical cohort of 100,000 patients assigned to each treatment arm, in the CR arm, there would be an estimated 16,678 hospitalizations and 3,854 surgeries and 51,479 patients would require dose escalation for LOR (Figure 1). In contrast, in the MH arm, a greater number of patients (n=56,686) would be dose escalated but a small number would require surgery (n=2,907) or hospitalization (n=12,934). The number needed to treat (NNT) with the MH strategy to prevent one excess surgery was 106 while the corresponding NNT to prevent a hospitalization was 27. Conclusion: We demonstrate that mucosal healing may be a cost-effective endpoint in CD patients initiating IFX therapy. Further prospective studies on durability of mucosal healing and its incremental benefit as well as the ability
AGA Abstracts
S-654
PDAI score was 2 (range 0-13) with 31 patients (11.3%) having pouchitis and 8 (2.9%) having inflammation of the afferent limb, based on the PDAI criteria. The median PAS was 8 (range: 0-20) with 45 patients (16.4%) having pouchitis and 12 (4.3%) having inflammation of the afferent limb, based on these criteria. The clinical components of both PDAI and PAS were found to highly correlate with the total scores, with CC's of 0.66 and 0.7 for the PDAI and PAS respectively. Poor correlations were found between the clinical and the endoscopic or histological parts of the indices with CC's of 0.18 and 0.07 for the clinical to endoscopic and acute histological findings respectively using the PDAI criteria and CC's of 0.2, 0.12 and 0.05 for clinical to endoscopic, acute histological and chronic histological findings respectively using the PAS criteria. Conclusions: There is poor correlation between clinical and endoscopic/histological scores in patients with IPAA. Clinical symptoms may not reflect endoscopic or histological evidence of inflammation. Further research is required to understand the relationship between the association of signs of pouch inflammation and clinical symptoms.
of other available biologic agents to achieve mucosal healing are necessary to validate our findings.
Mo1667 Lactoferrin Level is an Indicator of Mucosal Healing in Patients With Ulcerative Colitis: A Prospective 12-Month Monitoring Study Jost Langhorst, Andreas Rueffer, Marcus Baecker, Gustav J. Dobos, James H. Boone
Outcomes of a hypothetical cohort of 100,000 patients with moderate-to-severe Crohn's disease treated with infliximab
INTRODUCTION: Inflammatory bowel disease is challenging to manage and includes periods of disease activity and remission. Recent studies have identified a treatment goal of mucosal healing for optimal patient outcome and decrease in surgery. Fecal lactoferrin is a validated biomarker for intestinal inflammation and increased levels indicate active disease. AIMS & METHODS: In this study, we followed patients (pts) with inactive ulcerative colitis (CAI <5) for 12-months and evaluated C-reactive protein (CRP - cut-off: 0.5mg/dl), white blood cell count (WBC - cut-off: 8.5/nl), and fecal lactoferrin levels (FLA - cut-off: 7.25μg/g) as biomarkers for active disease and for determining mucosal healing. A total of 85 pts with inactive UC were evaluated at 6 different time-points (baseline, 1; 3; 6; 9; 12 month). Stool and serum specimens were collected for quantitative fecal lactoferrin by immunoassay and lab parameters (CRP and WBC), respectively. Sigmoidoscopy with histology was performed at baseline, in the event of an acute flare (CAI>4) or at the end of the 12 month period to determined the presence of mucosal inflammation. Endoscopy score was used for defining mucosal healing. In addition, absence of acute immune cell infiltration, crypt abscess, mucin depletion and breaches in the surface epithelium (Riley Score) was used for defining histological healing. RESULTS: There were 85 patients, male-female ratio 1:1 and age range 20 to 75 years that were monitored for the complete 12-months. A total of 36 pts suffered a flare and 49 pts experienced sustained remission using CAI. Median FLA levels were 40μg/ g vs 5μg/g (p<0.0001), median CRP levels 0.6mg/dl vs 0.1mg/dl (p<0.001) and median WBC levels 7.6 vs 6.0/nl (p=0.01) for flare vs remission, respectively. Of the pts in sustained remission, 44 achieved mucosal healing based on Endoscopy Score 0-1 (Rachmilewitz). Median levels (at 12 month) of pts with mucosal healing and pts with mucosal activity were 5μg/g vs 37μg/g for FLA (p=0.09), 0.2mg/dl vs 0.1mg/dl for CRP (p=0.882) and 5.9 vs 6.0/ nl for WBC (p=0.787), respectively. Of the pts in sustained remission, 41 did not show any signs of acute histological activity (Riley Score). Median levels (at 12 month) of pts without signs of acute histological activity and pts with signs of acute histological activity were 4.6μg/ g vs 14.4μg/g for FLA (p=0.198), 0.2mg/dl vs 0.1mg/dl for CRP (p=0.948) and 6.0 vs 6.0/ nl for WBC (p=0.759), respectively. FLA was the only biomarker to show a median level above cut-off for active disease defined by endoscopy as well as histology for pts in sustained clinical remission. CONCLUSION: Our results show that fecal lactoferrin is a useful biomarker for identifying active UC and for determining patients that achieve mucosal healing.
Mo1669 Correlation Between Serological Biomarkers and Clinical Activity in Patients With Inflammatory Bowel Disease (IBD) Pablo Miranda-García, Maria Chaparro, Javier P. Gisbert Background: Biomarkers are used routinely to monitor activity in patients with IBD. However, the correlation between these markers and clinical disease activity is not well established. Objectives: To evaluate the correlation between several serological biomarkers and clinical activity in patients with IBD. To identify the serological biomarkers with the best accuracy to assess the clinical activity in patients with IBD. Methods: Patients followed-up at the IBD Unit from our hospital were prospectively included. A blood sample was obtained from each patient and haematological parameters and several biomarkers were determined: Creactive protein (CRP), orosomucoid, erythrocyte sedimentation rate (ESR), ferritin, and fibrinogen. The clinical activity was assessed by the Partial Mayo Score in the case of ulcerative colitis (UC) and by the Harvey-Bradshaw activity index in Crohn's disease (CD) patients. The accuracy of each biomarker was assessed by the area under the ROC curve (AUC). The best cut-off value for each biomarker was identified; for it, sensitivity (Se), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV) were calculated. Results: Three-hundred and fifty patients were included. The median age was 46 years and the median time of evolution of the disease was 3 years, 52% were female and 59% had CD. The overall accuracy and the accuracy for CD and UC of the best serological biomarkers are shown in the tables. Conclusions: The correlation between commonly used serological biomarkers and the clinical activity of IBD is low. The accuracy of these markers is, in general, worse in UC than in CD. CRP, fibrinogen and haemoglobin have the best correlation with the clinical activity in CD. Overall accuracy (CD and UC)
Mo1668 Mucosal Healing is a Cost-Effective Endpoint With Biologic Therapy in Crohns Disease − Results From a Decision Analysis Ashwin N. Ananthakrishnan, Joshua R. Korzenik, Chin Hur Introduction: Observational studies have demonstrated that mucosal healing may be associated with reduction in the need for hospitalizations or surgeries for moderate to severe Crohn's disease (CD). Infliximab (IFX) has demonstrated that it is possible to achieve and maintain endoscopic healing in CD. Whether treatment to achieve mucosal healing is a costeffective endpoint has not been established previously. Methods: We constructed a decision analytic model comparing two treatment strategies for patients with moderate-to-severe CD initiating treatment with IFX. In the clinical response (CR) arm, patients without clinical response or remission at year 1 are dose escalated. In the mucosal healing (MH) arm, patients with persistence of mucosal ulceration at year 1 undergo treatment escalation irrespective of clinical symptoms. Patients were modeled to remain at risk for hospitalization and surgeries while they have active disease. The model encompassed a 2 year time horizon. Results: In the base case, the MH strategy was more effective at 2 years (QALY 0.71) compared to the CR strategy (QALY 0.69) but was also more expensive with an estimated cost of $58,386 compared to the CR strategy ($57,195) for an ICER of $47,502/QALY gained. Our results were sensitive to the ability of existing biologic therapies to achieve clinical response as well as endoscopic healing. For clinical response rates of < 48% at year 1, the MH strategy was the dominant (both more effective and less costly) strategy. For the CR arm to be dominant required a clinical response rate > 72%. For clinical response rates > 57%, the ICER associated with MH was above the willingness-to-pay threshold. Conversely, if the likelihood of mucosal healing at 1 year was > 54%, the MH strategy was dominant. Alternatively expressed, for ratios of mucosal healing to clinical response of 0.84 or higher, the MH strategy was costeffective. In a hypothetical cohort of 100,000 patients assigned to each treatment arm, in the CR arm, there would be an estimated 16,678 hospitalizations and 3,854 surgeries and 51,479 patients would require dose escalation for LOR (Figure 1). In contrast, in the MH arm, a greater number of patients (n=56,686) would be dose escalated but a small number would require surgery (n=2,907) or hospitalization (n=12,934). The number needed to treat (NNT) with the MH strategy to prevent one excess surgery was 106 while the corresponding NNT to prevent a hospitalization was 27. Conclusion: We demonstrate that mucosal healing may be a cost-effective endpoint in CD patients initiating IFX therapy. Further prospective studies on durability of mucosal healing and its incremental benefit as well as the ability
AGA Abstracts
S-654