- Email: [email protected]
W1165 Clinical Assessment of Ulcerative Colitis Activity Correlates Poorly with Endoscopic Disease Activity.
AGA Abstracts
revealed that the C patients had a stronger correlation (Pearson's R2=0.2991, p=0.0032) than the AA patients (Pearson's R2=0.1112, p=0.0502). Although not significant, there was a trend toward a correlation between the NLR and an increased number of UC flares (p= 0.07). Conclusion: Our data indicate that there is a correlation between the NLR and length of stay among patients diagnosed with UC and that this correlation may be stronger in the Caucasian population. The NLR might be a simple test that can be implemented to detect disease severity among UC patients presenting to the hospital for admission.
W1166 A New Simple Highly Accurate Quantitative Disease Activity Index with Improved Correlation to Endoscopy for Assessing Intestinal Inflammation in IBD Jost Langhorst, James H. Boone, Andreas Rueffer, Gustav J. Dobos Background: Assessing active disease in patients with inflammatory bowel disease (IBD) is essential for optimal medical therapy. Common activity indices like the Crohns Disease Activity Index (CDAI) show poor correlation to ileocolonoscopy. Serologic parameters such as C-reactive protein (CRP) are hampered by a low sensitivity and specificity for intestinal inflammation. Lactoferrin, a neutrophil-derived protein, has been shown to be a useful biomarker for measuring intestinal inflammation in ulcerative colitis (UC) and Crohns disease (CD). Aim: To develop and evaluate a simple quantitative activity index that combines fecal lactoferrin (FLA), CRP and clinical symptoms for assessing disease activity of patients with IBD. Methods: A total of 127 adult IBD patients (62 CD and 65 UC, mean age 43 yr, male:female ratio 1:2) were classified for disease status by ileocolonoscopy and histopathology using a score of 0-3 (0 = no to 3 = high inflammation). Serum and fecal specimens were analyzed for elevated serum CRP (≥ 0.5 mg/dl) and FLA (≥ 7 μg/ml), respectively, using enzyme-linked immunoassay (EIA). A new and simple index including the number of bowel movements, blood in stool, FLA and CRP results was calculated for UC and CD patients (a score of > 3 indicating active disease). For comparison, classical indices were calculated for UC using the Colitis Activity Index (CAI - Rachmilewitz-Index; > 5 indicating active disease) and for CD with the CDAI (> 150 indicating active disease). Results: Of the 62 CD and 65 UC patients, 50 and 43, respectively showed endoscopic signs of inflammation. CRP results correlated better with disease activity in UC compared to CD (71vs55%) and showed poor correlation with CD ileal disease. FLA showed a correlation to endoscopy of 76% in UC and 79% in CD and performed consistently across disease location in CD patients. The CDAI showed a sensitivity and correlation to endoscopy of 22% and 37%, and the CAI of 77 and 88%. Our new activity index that includes both CRP and FLA improved the sensitivity and correlation to endoscopy over the CDAI to 82% and 76%, and the CAI to 84% and 88%. Using a secondary cut-off of >6 for our new index to indicate moderate to severe disease, 79% of severe CD and 100% of severe UC patients were positive ranging from 7 to 16. Conclusion: FLA outperforms CRP for detecting intestinal inflammation. Our new and simple activity index including both biomarkers showed an improved correlation to ileocolonoscopy for both CD and UC. Preliminary data suggests that an quantitative activity index that includes both FLA and CRP may be useful for determining the effectiveness of treatment in IBD.
W1164 Importance of Peripheral Immune Cell Activity and Maladaptive Stress Reaction for Disease Activity At the Onset of Ulcerative Colitis Hans Strid, Berndt Johansson, Jan Svedlund, Magnus Simren, Lena Ohman Background: The understanding of underlying factors resulting in the individual variation of the disease severity and extent of the mucosal inflammation in ulcerative colitis (UC) is limited. Aim: The aim of this study was to investigate if peripheral immune activity and the presence of maladaptive stress reaction correlated to the disease activity or colonic disease presentation at the onset of UC. Methods: Blood samples were analysed from 93 untreated patients (32 women, age 32(25-44) within the first weeks of UC onset. The colonic disease activity, according to Mayo score, and the intestinal presentation of the disease, was established during colonoscopy. Peripheral blood mononuclear cells were isolated and the antiCD3/CD28 induced blood T cell cytokine secretion was analysed with LUMINEX. The psychiatric evaluation was based on a standardised diagnostic interview (SCID-P) in accordance with the Diagnostic and Statistical Manual of Mental Disorders (DSM IV). This is a semi-structured interview for making DSM diagnoses which is designed for use by trained clinicians. In this study a psychiatrist performed the interview 3 months after the patient's first visit to the medicine clinic Results: There was not any difference in either activity, according to Mayo score, or intestinal presentation of the disease between patients with or without current maladaptive stress reaction, according to DSM IV, at the time for onset of disease. However, patients with maladaptive stress reaction (n=10) had a lower T cell secretion of the proinflammatory cytokine TNF-alfa (7336±13045 vs 11288±12273, p=0.03) and tended to have a decreased secretion of the inflammatory cytokine IFN-gamma (598±340 vs 784± 434, p=0.18) and the regulatory cytokine IL-10 (407±437 vs 809± 816, p=0.10) as compared to patients without maladaptive stress reaction. Furthermore, the T cell secretion of IFN-gamma (r=-0.277, p=0.006) and IL-10 (r=-0.243, p=0.02) was negatively correlated to disease activity. Thus, patients with extensive colitis (661±404) demonstrated lower levels of T cell secreted IFN-gamma as compared to patients with proctitis (1059±312, p=0.003) or with left sided dominated inflammation (850±434, p=0.04). Also, patients with extensive colitis (660±773) demonstrated lower levels of T cell secreted IL-10 as compared to patients with proctitis (1155±759, p=0.05) but not with left sided dominated inflammation (808±775, p=0.4). Conclusion: Activity and extent of UC may be reflected by the peripheral immune cell activity. Patients with maladaptive stress reaction had a reduced T cell cytokine secretion, which might indicate a correlation between stress and inflammation in UC.
W1167 Patient's Functional Assessment (PFA) Provides Insight Into the Patient's Perception for Onset of Action Using Delayed-Release Mesalamine for Ulcerative Colitis (UC) Charles A. Sninsky, David Ramsey Purpose: Patient reported outcomes are becoming a topic of interest. Most UC trials focus on symptom and endoscopic improvement at certain time periods thereby limiting ability to address the patient's perception of onset of action. The purpose of this analysis was to evaluate PFA in patients with mildly to moderately active UC receiving delayed-release mesalamine 2.4g/d. Methods: Data from 2 randomized, double-blind, active-controlled, 6wk studies of similar design(ASCEND I&II) were combined & analyzed. This analysis includes data from the delayed-release mesalamine 2.4g/d (400mg tab) active-control arms. PFA was assessed on a 4-pt scale (0-3,indicating feeling generally well to terrible). Feeling “better” was defined as a decrease from baseline of ≥ 1-pt in PFA assessment. Feeling “generally well” was defined as a score of 0 on PFA assessment. The median time to feeling “better” or “generally well” was defined as number of days between the first day of dosing and first day of improvement/resolution based on PFA assessment recorded by patients through a daily interactive voice response system. Results: A total of 687 patients were randomized in the 2 studies of which 349 received 2.4g/d. The median time to feeling “better” or “generally well” was 3days(95% CI;2,3) and 7days(95% CI;5,8), respectively (Figure). The median time to improvement or resolution of symptoms was 5days(95% CI;4,5) and 10days(95% CI;8,13), respectively, for rectal bleeding and 5days(95% CI;4,5) and 11days(95% CI;8,15) for stool frequency. Conclusion: Delayed-release mesalamine 2.4g/ d helps mildly to moderately active UC patients feel better quickly. PFA is clinically important as it reflects the patient's assessment of how they feel-without interpretation by a healthcare professional. While PFA may be influenced by many factors including clinical improvement and anticipation bias, it may serve as an important assessment.
W1165 Clinical Assessment of Ulcerative Colitis Activity Correlates Poorly with Endoscopic Disease Activity. Joseph F. Rodemann, Kevin Kip, David G. Binion, Melissa Saul, Leonard Baidoo, Janet Harrison, Andrew R. Watson, Wolfgang H. Schraut, Miguel Regueiro Background: Subjective physician global assessment is the cornerstone of routine ulcerative colitis (UC) outpatient management. Endoscopic and histologic assessment of UC mucosa may provide objective measure of disease activity. The correlation of physician impression of UC disease activity (DA) in the clinic with endoscopic and histologic DA has not been assessed. Aims: Assess concordance between clinical impression of UCDA and endoscopic and histologic findings of DA. Methods: Using the Medical Archival Retrieval System at the Univ of Pittsburgh Medical Center we reviewed clinical information on all UC pts between 1/1/95 and 6/30/08. Clinical UCDA was defined by the physician's clinical impression; the descriptors “exacerbation of disease of mild, moderate, severe activity” meant “clinically active UC.” Endoscopic DA was defined as active UC when associated with any of the following terms, “erythema, edema, friability ulceration, inflammation, active disease, active UC.” Histologic DA was defined active UC if there was evidence of “cryptitis, crypt abscesses, infiltration of plasma cells or neutrophils, or the pathology impression was ‘consistent with active UC.'” Results: There were 428 UC pts who had a paired clinic visit and colonoscopy within 1 month. The mean age was 46 + 16 y (51% F). Active UC was 41% by clinical impression compared to 58% by colonoscopy and 66% by histology. Using endoscopy as the gold standard for defining UCDA, clinical activity demonstrated weak overall concordance (kappa=0.35) whereas histologic activity showed strong concordance (kappa=0.67). Similarly, clinical DA showed weak concordance with histologic DA (kappa=0.23). The most frequent discordance observed was a lack of perceived clinical DA in the presence of endoscopic DA (i.e. false negative). Conclusion: Clinical impression of active UC correlates poorly with endoscopic and histologic evaluation and underestimates mucosal inflammation. Impact of subclinical UC inflammation on durability of remission and progression to dysplasia/cancer warrants further evaluation.
AGA Abstracts
A-668
revealed that the C patients had a stronger correlation (Pearson's R2=0.2991, p=0.0032) than the AA patients (Pearson's R2=0.1112, p=0.0502). Although not significant, there was a trend toward a correlation between the NLR and an increased number of UC flares (p= 0.07). Conclusion: Our data indicate that there is a correlation between the NLR and length of stay among patients diagnosed with UC and that this correlation may be stronger in the Caucasian population. The NLR might be a simple test that can be implemented to detect disease severity among UC patients presenting to the hospital for admission.
W1166 A New Simple Highly Accurate Quantitative Disease Activity Index with Improved Correlation to Endoscopy for Assessing Intestinal Inflammation in IBD Jost Langhorst, James H. Boone, Andreas Rueffer, Gustav J. Dobos Background: Assessing active disease in patients with inflammatory bowel disease (IBD) is essential for optimal medical therapy. Common activity indices like the Crohns Disease Activity Index (CDAI) show poor correlation to ileocolonoscopy. Serologic parameters such as C-reactive protein (CRP) are hampered by a low sensitivity and specificity for intestinal inflammation. Lactoferrin, a neutrophil-derived protein, has been shown to be a useful biomarker for measuring intestinal inflammation in ulcerative colitis (UC) and Crohns disease (CD). Aim: To develop and evaluate a simple quantitative activity index that combines fecal lactoferrin (FLA), CRP and clinical symptoms for assessing disease activity of patients with IBD. Methods: A total of 127 adult IBD patients (62 CD and 65 UC, mean age 43 yr, male:female ratio 1:2) were classified for disease status by ileocolonoscopy and histopathology using a score of 0-3 (0 = no to 3 = high inflammation). Serum and fecal specimens were analyzed for elevated serum CRP (≥ 0.5 mg/dl) and FLA (≥ 7 μg/ml), respectively, using enzyme-linked immunoassay (EIA). A new and simple index including the number of bowel movements, blood in stool, FLA and CRP results was calculated for UC and CD patients (a score of > 3 indicating active disease). For comparison, classical indices were calculated for UC using the Colitis Activity Index (CAI - Rachmilewitz-Index; > 5 indicating active disease) and for CD with the CDAI (> 150 indicating active disease). Results: Of the 62 CD and 65 UC patients, 50 and 43, respectively showed endoscopic signs of inflammation. CRP results correlated better with disease activity in UC compared to CD (71vs55%) and showed poor correlation with CD ileal disease. FLA showed a correlation to endoscopy of 76% in UC and 79% in CD and performed consistently across disease location in CD patients. The CDAI showed a sensitivity and correlation to endoscopy of 22% and 37%, and the CAI of 77 and 88%. Our new activity index that includes both CRP and FLA improved the sensitivity and correlation to endoscopy over the CDAI to 82% and 76%, and the CAI to 84% and 88%. Using a secondary cut-off of >6 for our new index to indicate moderate to severe disease, 79% of severe CD and 100% of severe UC patients were positive ranging from 7 to 16. Conclusion: FLA outperforms CRP for detecting intestinal inflammation. Our new and simple activity index including both biomarkers showed an improved correlation to ileocolonoscopy for both CD and UC. Preliminary data suggests that an quantitative activity index that includes both FLA and CRP may be useful for determining the effectiveness of treatment in IBD.
W1164 Importance of Peripheral Immune Cell Activity and Maladaptive Stress Reaction for Disease Activity At the Onset of Ulcerative Colitis Hans Strid, Berndt Johansson, Jan Svedlund, Magnus Simren, Lena Ohman Background: The understanding of underlying factors resulting in the individual variation of the disease severity and extent of the mucosal inflammation in ulcerative colitis (UC) is limited. Aim: The aim of this study was to investigate if peripheral immune activity and the presence of maladaptive stress reaction correlated to the disease activity or colonic disease presentation at the onset of UC. Methods: Blood samples were analysed from 93 untreated patients (32 women, age 32(25-44) within the first weeks of UC onset. The colonic disease activity, according to Mayo score, and the intestinal presentation of the disease, was established during colonoscopy. Peripheral blood mononuclear cells were isolated and the antiCD3/CD28 induced blood T cell cytokine secretion was analysed with LUMINEX. The psychiatric evaluation was based on a standardised diagnostic interview (SCID-P) in accordance with the Diagnostic and Statistical Manual of Mental Disorders (DSM IV). This is a semi-structured interview for making DSM diagnoses which is designed for use by trained clinicians. In this study a psychiatrist performed the interview 3 months after the patient's first visit to the medicine clinic Results: There was not any difference in either activity, according to Mayo score, or intestinal presentation of the disease between patients with or without current maladaptive stress reaction, according to DSM IV, at the time for onset of disease. However, patients with maladaptive stress reaction (n=10) had a lower T cell secretion of the proinflammatory cytokine TNF-alfa (7336±13045 vs 11288±12273, p=0.03) and tended to have a decreased secretion of the inflammatory cytokine IFN-gamma (598±340 vs 784± 434, p=0.18) and the regulatory cytokine IL-10 (407±437 vs 809± 816, p=0.10) as compared to patients without maladaptive stress reaction. Furthermore, the T cell secretion of IFN-gamma (r=-0.277, p=0.006) and IL-10 (r=-0.243, p=0.02) was negatively correlated to disease activity. Thus, patients with extensive colitis (661±404) demonstrated lower levels of T cell secreted IFN-gamma as compared to patients with proctitis (1059±312, p=0.003) or with left sided dominated inflammation (850±434, p=0.04). Also, patients with extensive colitis (660±773) demonstrated lower levels of T cell secreted IL-10 as compared to patients with proctitis (1155±759, p=0.05) but not with left sided dominated inflammation (808±775, p=0.4). Conclusion: Activity and extent of UC may be reflected by the peripheral immune cell activity. Patients with maladaptive stress reaction had a reduced T cell cytokine secretion, which might indicate a correlation between stress and inflammation in UC.
W1167 Patient's Functional Assessment (PFA) Provides Insight Into the Patient's Perception for Onset of Action Using Delayed-Release Mesalamine for Ulcerative Colitis (UC) Charles A. Sninsky, David Ramsey Purpose: Patient reported outcomes are becoming a topic of interest. Most UC trials focus on symptom and endoscopic improvement at certain time periods thereby limiting ability to address the patient's perception of onset of action. The purpose of this analysis was to evaluate PFA in patients with mildly to moderately active UC receiving delayed-release mesalamine 2.4g/d. Methods: Data from 2 randomized, double-blind, active-controlled, 6wk studies of similar design(ASCEND I&II) were combined & analyzed. This analysis includes data from the delayed-release mesalamine 2.4g/d (400mg tab) active-control arms. PFA was assessed on a 4-pt scale (0-3,indicating feeling generally well to terrible). Feeling “better” was defined as a decrease from baseline of ≥ 1-pt in PFA assessment. Feeling “generally well” was defined as a score of 0 on PFA assessment. The median time to feeling “better” or “generally well” was defined as number of days between the first day of dosing and first day of improvement/resolution based on PFA assessment recorded by patients through a daily interactive voice response system. Results: A total of 687 patients were randomized in the 2 studies of which 349 received 2.4g/d. The median time to feeling “better” or “generally well” was 3days(95% CI;2,3) and 7days(95% CI;5,8), respectively (Figure). The median time to improvement or resolution of symptoms was 5days(95% CI;4,5) and 10days(95% CI;8,13), respectively, for rectal bleeding and 5days(95% CI;4,5) and 11days(95% CI;8,15) for stool frequency. Conclusion: Delayed-release mesalamine 2.4g/ d helps mildly to moderately active UC patients feel better quickly. PFA is clinically important as it reflects the patient's assessment of how they feel-without interpretation by a healthcare professional. While PFA may be influenced by many factors including clinical improvement and anticipation bias, it may serve as an important assessment.
W1165 Clinical Assessment of Ulcerative Colitis Activity Correlates Poorly with Endoscopic Disease Activity. Joseph F. Rodemann, Kevin Kip, David G. Binion, Melissa Saul, Leonard Baidoo, Janet Harrison, Andrew R. Watson, Wolfgang H. Schraut, Miguel Regueiro Background: Subjective physician global assessment is the cornerstone of routine ulcerative colitis (UC) outpatient management. Endoscopic and histologic assessment of UC mucosa may provide objective measure of disease activity. The correlation of physician impression of UC disease activity (DA) in the clinic with endoscopic and histologic DA has not been assessed. Aims: Assess concordance between clinical impression of UCDA and endoscopic and histologic findings of DA. Methods: Using the Medical Archival Retrieval System at the Univ of Pittsburgh Medical Center we reviewed clinical information on all UC pts between 1/1/95 and 6/30/08. Clinical UCDA was defined by the physician's clinical impression; the descriptors “exacerbation of disease of mild, moderate, severe activity” meant “clinically active UC.” Endoscopic DA was defined as active UC when associated with any of the following terms, “erythema, edema, friability ulceration, inflammation, active disease, active UC.” Histologic DA was defined active UC if there was evidence of “cryptitis, crypt abscesses, infiltration of plasma cells or neutrophils, or the pathology impression was ‘consistent with active UC.'” Results: There were 428 UC pts who had a paired clinic visit and colonoscopy within 1 month. The mean age was 46 + 16 y (51% F). Active UC was 41% by clinical impression compared to 58% by colonoscopy and 66% by histology. Using endoscopy as the gold standard for defining UCDA, clinical activity demonstrated weak overall concordance (kappa=0.35) whereas histologic activity showed strong concordance (kappa=0.67). Similarly, clinical DA showed weak concordance with histologic DA (kappa=0.23). The most frequent discordance observed was a lack of perceived clinical DA in the presence of endoscopic DA (i.e. false negative). Conclusion: Clinical impression of active UC correlates poorly with endoscopic and histologic evaluation and underestimates mucosal inflammation. Impact of subclinical UC inflammation on durability of remission and progression to dysplasia/cancer warrants further evaluation.
AGA Abstracts
A-668