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Sa1192 Predictors of Indeterminate QuantiFERON-TB Gold Testing in Inflammatory Bowel Disease and Impact on Clinical Outcomes
AGA Abstracts
TABLE 2: Inflammatory bowel disease morbidity by QuantiFERON-TB Gold result
*New development of chronic pouchitis, chronic cuffitis or CD of the pouch Table 2. Limited multivariate analysis for risk factors associated with composite adverse pouch outcomes
Sa1192 Predictors of Indeterminate QuantiFERON-TB Gold Testing in Inflammatory Bowel Disease and Impact on Clinical Outcomes Ravy K. Vajravelu, Mark T. Osterman, Faten Aberra, Gary R. Lichtenstein, James Lewis, Frank I. Scott
* indicates p < 0.05
Sa1193 BACKGROUND: The American Gastroenterological Association recommends screening for latent tuberculosis infection (LTBI) prior to initiating anti-TNF therapy . QuantiFERON-TB Gold (QFTG) is an interferon-gamma release assay used to diagnose LTBI. Many clinics have adopted this assay due to ease of performance. However, indeterminate results may occur when a patient's blood sample does not react with a positive control. Prior studies attempting to define risk factors for indeterminate QFTG have been limited in size. AIMS: To determine risk factors for indeterminate QFTG in inflammatory bowel disease (IBD) patients and to assess how indeterminate results may impact care. METHODS: A systematic review of the electronic medical record of a tertiary medical center was performed for patients from 2009 - 2014 with an ICD-9 code for IBD (555.x and 556.x) and a CPT code for QFTG (86480). Age, sex, race, IBD subtype, medications, and location of care at the time of QTFG were measured in a stratified, random subset of patients. Logistic regression was employed to identify factors associated with an indeterminate result. Subsequent clinical outcomes including time to medication change, hospitalization, flare, and surgery were determined from review of progress notes and compared via c2 testing. RESULTS: 413 IBD patients who had undergone QFTG testing were identified. 320 QFTGs were negative, 82 were indeterminate, and 11 were positive. 49 indeterminate and 51 negative QFTGs were then randomly selected. Testing during hospitalization (OR 5.32, 95% CI 2.15 - 13.05) and systemic steroid use (OR 5.00, 95% CI 1.86 - 13.46) were associated with an increased risk of indeterminate results (TABLE 1). Other medications were not associated with indeterminate results. White race and age <45 were also associated with increased odds of indeterminate QFTG. Multivariate regression was consistent with univariate regression results. There was a delay of at least 1 month in planned medication changes in 16% of indeterminate tests and 2% of negative tests (p = 0.008). Within 60 days, rates of hospitalization (20% vs 8%, p=0.058) and IBD-related surgery (10% vs 2%, p=0.073) were greater in those with indeterminate results (TABLE 2). Of selected indeterminate tests, 17 (35%) were later repeated, with 14 negative and 3 indeterminate on retest. No patients with indeterminate results developed tuberculosis. CONCLUSIONS: Steroid use and hospitalization are risk factors for indeterminate QFTG, possibly due to T-cell suppression in patients with active IBD. Indeterminate results may significantly impact care via delays in initiating medications, leading to increased rates of subsequent hospitalization and surgery. These data will help to determine which patients require alternative initial LTBI screening methods to maximize diagnostic yield and prevent morbidity from decision-making delays. TABLE 1: Univariate logistic regression for indeterminate QuantiFERON-TB Gold (n = 100)
Ulcerative Proctitis: Predictors and Outcomes of Disease Extension in UC Karen Boland, Orlaith B. Kelly, Kieran Sheahan, Hugh Mulcahy, Denise Keegan, Garret Cullen, Glen A. Doherty Ulcerative proctitis is a variant of ulcerative colitis anatomically limited to the rectum. Proximal disease extension in these patients is associated with a poor prognosis. We studied outcomes of patients diagnosed with ulcerative proctitis who demonstrate extension of their disease, seeking to identify associated risk factors. We compared prognosis with patients who have extensive disease at presentation. This is a retrospective study of a prospectively maintained electronic database of 3,200 patients with IBD attending a single centre. Patients diagnosed with histologically confirmed ulcerative proctitis were identified. Those with disease extension were compared to patients with stable limited proctitis. A retrospective review of clinical, endoscopic and histological records was performed to determine disease course and define predictors of proximal extension. 481 patients with an initial diagnosis of ulcerative proctitis were identified. Records of 109 patients with stable limited proctitis, 42 patients with proctitis and subsequent disease extension, and 60 patients with pancolitis at diagnosis were analysed with comparable follow up periods. Disease extension occurred within 1 year of diagnosis in 33.3%, in 45.2% within 1-5 years and in 21.4% within 6-20 years. Factors associated with extension included non-smoking (p = 0.02, Fishers exact test), and more severe disease course characterised by greater use of immunosuppression (p < 0.001, Fishers exact test), prescription of systemic corticosteroids at diagnosis (43.9% extenders, 10.9% limited proctitis, p <0.001, Fishers exact test) and a history of >2 hospital admissions from diagnosis over a mean period of 3.4 years (6 mths - 18 yrs) (p = 0.006, Fishers exact test). Features not predictive of disease extension included family history of IBD, age at diagnosis, and extra-intestinal manifestations of disease. Proximally extended patients were more likely to need surgery (45.23%) during a follow up period of 18 months to 12 years than patients with extensive disease at index presentation (23.3%, p <0.03, Fishers exact test). Early disease extension within 1 year of diagnosis is more likely to lead to colectomy (p <0.01, Gehan-Breslow-Wilcoxon Test) with median time to colectomy of 3 years. Proximal disease extension in patients with proctitis is more common in nonsmokers and is associated with a more refractory disease course with greater requirement for immunosuppressant use as well as a history of oral or parenteral corticosteroids at diagnosis. These patients are more vulnerable to failure of medical therapy and more likely to require colectomy than patients with extensive disease at diagnosis. Hence, proctitis with proximal disease extension is a poor prognostic indicator and greater understanding of the biology of this phenomenon might facilitate disease modifying treatments strategies.
Sa1194 Consistently High C Reactive Protein Is Associated With Subsequent Development of Perianal Fistulae in Patients With Crohn's Disease James R. Irwin, Emma Ferguson, Lisa A. Simms, Katherine Hanigan, Graham L. RadfordSmith BACKGROUND: Laboratory tests are used longitudinally in the management of patients with Crohn's disease. Whether there is a correlation between longitudinal laboratory results and the subsequent development of perianal disease is unknown. AIM: To study the correlation between longitudinal laboratory testing and subsequent development of perianal fistula in patients with Crohn's disease. METHODS: Patients diagnosed at a tertiary referral centre with Crohn's disease between 1st Jan 1994 and 1st March 2008, with more than five years of clinical follow-up, had objective clinical, laboratory and genetic data recorded. Patients with a perianal fistula occurring within 6 months of diagnosis were excluded. Laboratory data were represented by the area under the curve of values measured in the complication free period leading up to development of a perianal fistula. Cox regression was used to analyse the association between development of a perianal fistula and laboratory values for: C reactive protein (CRP), platelet count, albumin level, faecal calprotectin, serum ferritin, serum haemoglobin and erythrocyte sedimentation rate (ESR). Laboratory values were converted to categorical variables with optimized cut-offs. Recognized predictors of development of perianal disease were added to the model to assess independence of identified associations. RESULTS: 382 patients were reviewed, of whom 57 had less than five years of clinical follow-up and 43 had perianal disease within 6 months of diagnosis. 257 had a complete clinical, biochemical and genetic record without perianal disease at diagnosis and were observed for a median of 10.25 (interquartile range (IQR) 7.39-13.78) years. Blood testing was performed a median of 3.61 (IQR 2.24 - 5.79) times per year for each patient. 46 patients developed a perianal fistula a median of 2.06 (IQR 1.10 - 5.82) years after diagnosis. Results of univariate analysis are tabulated. After multivariate analysis with inclusion of recognised predictor variables, CRP >31 (HR 7.12, p<0.001) and age at diagnosis <32 (HR 3.93, p=0.004) were independently associated with development of perianal fistula. CONCLUSION: A longitudinally measured CRP consistently greater than 31 is independently associated with subsequent development of a perianal fistula in patients with Crohn's disease.
* indicates p < 0.05; ** Multivariate model includes all significant variables in univariate analysis; Abbreviations: SS = systemic steroids (oral prednisone and IV methylprednisolone, excludes budesonide), IM = immunomodulators
S-253
AGA Abstracts
TABLE 2: Inflammatory bowel disease morbidity by QuantiFERON-TB Gold result
*New development of chronic pouchitis, chronic cuffitis or CD of the pouch Table 2. Limited multivariate analysis for risk factors associated with composite adverse pouch outcomes
Sa1192 Predictors of Indeterminate QuantiFERON-TB Gold Testing in Inflammatory Bowel Disease and Impact on Clinical Outcomes Ravy K. Vajravelu, Mark T. Osterman, Faten Aberra, Gary R. Lichtenstein, James Lewis, Frank I. Scott
* indicates p < 0.05
Sa1193 BACKGROUND: The American Gastroenterological Association recommends screening for latent tuberculosis infection (LTBI) prior to initiating anti-TNF therapy . QuantiFERON-TB Gold (QFTG) is an interferon-gamma release assay used to diagnose LTBI. Many clinics have adopted this assay due to ease of performance. However, indeterminate results may occur when a patient's blood sample does not react with a positive control. Prior studies attempting to define risk factors for indeterminate QFTG have been limited in size. AIMS: To determine risk factors for indeterminate QFTG in inflammatory bowel disease (IBD) patients and to assess how indeterminate results may impact care. METHODS: A systematic review of the electronic medical record of a tertiary medical center was performed for patients from 2009 - 2014 with an ICD-9 code for IBD (555.x and 556.x) and a CPT code for QFTG (86480). Age, sex, race, IBD subtype, medications, and location of care at the time of QTFG were measured in a stratified, random subset of patients. Logistic regression was employed to identify factors associated with an indeterminate result. Subsequent clinical outcomes including time to medication change, hospitalization, flare, and surgery were determined from review of progress notes and compared via c2 testing. RESULTS: 413 IBD patients who had undergone QFTG testing were identified. 320 QFTGs were negative, 82 were indeterminate, and 11 were positive. 49 indeterminate and 51 negative QFTGs were then randomly selected. Testing during hospitalization (OR 5.32, 95% CI 2.15 - 13.05) and systemic steroid use (OR 5.00, 95% CI 1.86 - 13.46) were associated with an increased risk of indeterminate results (TABLE 1). Other medications were not associated with indeterminate results. White race and age <45 were also associated with increased odds of indeterminate QFTG. Multivariate regression was consistent with univariate regression results. There was a delay of at least 1 month in planned medication changes in 16% of indeterminate tests and 2% of negative tests (p = 0.008). Within 60 days, rates of hospitalization (20% vs 8%, p=0.058) and IBD-related surgery (10% vs 2%, p=0.073) were greater in those with indeterminate results (TABLE 2). Of selected indeterminate tests, 17 (35%) were later repeated, with 14 negative and 3 indeterminate on retest. No patients with indeterminate results developed tuberculosis. CONCLUSIONS: Steroid use and hospitalization are risk factors for indeterminate QFTG, possibly due to T-cell suppression in patients with active IBD. Indeterminate results may significantly impact care via delays in initiating medications, leading to increased rates of subsequent hospitalization and surgery. These data will help to determine which patients require alternative initial LTBI screening methods to maximize diagnostic yield and prevent morbidity from decision-making delays. TABLE 1: Univariate logistic regression for indeterminate QuantiFERON-TB Gold (n = 100)
Ulcerative Proctitis: Predictors and Outcomes of Disease Extension in UC Karen Boland, Orlaith B. Kelly, Kieran Sheahan, Hugh Mulcahy, Denise Keegan, Garret Cullen, Glen A. Doherty Ulcerative proctitis is a variant of ulcerative colitis anatomically limited to the rectum. Proximal disease extension in these patients is associated with a poor prognosis. We studied outcomes of patients diagnosed with ulcerative proctitis who demonstrate extension of their disease, seeking to identify associated risk factors. We compared prognosis with patients who have extensive disease at presentation. This is a retrospective study of a prospectively maintained electronic database of 3,200 patients with IBD attending a single centre. Patients diagnosed with histologically confirmed ulcerative proctitis were identified. Those with disease extension were compared to patients with stable limited proctitis. A retrospective review of clinical, endoscopic and histological records was performed to determine disease course and define predictors of proximal extension. 481 patients with an initial diagnosis of ulcerative proctitis were identified. Records of 109 patients with stable limited proctitis, 42 patients with proctitis and subsequent disease extension, and 60 patients with pancolitis at diagnosis were analysed with comparable follow up periods. Disease extension occurred within 1 year of diagnosis in 33.3%, in 45.2% within 1-5 years and in 21.4% within 6-20 years. Factors associated with extension included non-smoking (p = 0.02, Fishers exact test), and more severe disease course characterised by greater use of immunosuppression (p < 0.001, Fishers exact test), prescription of systemic corticosteroids at diagnosis (43.9% extenders, 10.9% limited proctitis, p <0.001, Fishers exact test) and a history of >2 hospital admissions from diagnosis over a mean period of 3.4 years (6 mths - 18 yrs) (p = 0.006, Fishers exact test). Features not predictive of disease extension included family history of IBD, age at diagnosis, and extra-intestinal manifestations of disease. Proximally extended patients were more likely to need surgery (45.23%) during a follow up period of 18 months to 12 years than patients with extensive disease at index presentation (23.3%, p <0.03, Fishers exact test). Early disease extension within 1 year of diagnosis is more likely to lead to colectomy (p <0.01, Gehan-Breslow-Wilcoxon Test) with median time to colectomy of 3 years. Proximal disease extension in patients with proctitis is more common in nonsmokers and is associated with a more refractory disease course with greater requirement for immunosuppressant use as well as a history of oral or parenteral corticosteroids at diagnosis. These patients are more vulnerable to failure of medical therapy and more likely to require colectomy than patients with extensive disease at diagnosis. Hence, proctitis with proximal disease extension is a poor prognostic indicator and greater understanding of the biology of this phenomenon might facilitate disease modifying treatments strategies.
Sa1194 Consistently High C Reactive Protein Is Associated With Subsequent Development of Perianal Fistulae in Patients With Crohn's Disease James R. Irwin, Emma Ferguson, Lisa A. Simms, Katherine Hanigan, Graham L. RadfordSmith BACKGROUND: Laboratory tests are used longitudinally in the management of patients with Crohn's disease. Whether there is a correlation between longitudinal laboratory results and the subsequent development of perianal disease is unknown. AIM: To study the correlation between longitudinal laboratory testing and subsequent development of perianal fistula in patients with Crohn's disease. METHODS: Patients diagnosed at a tertiary referral centre with Crohn's disease between 1st Jan 1994 and 1st March 2008, with more than five years of clinical follow-up, had objective clinical, laboratory and genetic data recorded. Patients with a perianal fistula occurring within 6 months of diagnosis were excluded. Laboratory data were represented by the area under the curve of values measured in the complication free period leading up to development of a perianal fistula. Cox regression was used to analyse the association between development of a perianal fistula and laboratory values for: C reactive protein (CRP), platelet count, albumin level, faecal calprotectin, serum ferritin, serum haemoglobin and erythrocyte sedimentation rate (ESR). Laboratory values were converted to categorical variables with optimized cut-offs. Recognized predictors of development of perianal disease were added to the model to assess independence of identified associations. RESULTS: 382 patients were reviewed, of whom 57 had less than five years of clinical follow-up and 43 had perianal disease within 6 months of diagnosis. 257 had a complete clinical, biochemical and genetic record without perianal disease at diagnosis and were observed for a median of 10.25 (interquartile range (IQR) 7.39-13.78) years. Blood testing was performed a median of 3.61 (IQR 2.24 - 5.79) times per year for each patient. 46 patients developed a perianal fistula a median of 2.06 (IQR 1.10 - 5.82) years after diagnosis. Results of univariate analysis are tabulated. After multivariate analysis with inclusion of recognised predictor variables, CRP >31 (HR 7.12, p<0.001) and age at diagnosis <32 (HR 3.93, p=0.004) were independently associated with development of perianal fistula. CONCLUSION: A longitudinally measured CRP consistently greater than 31 is independently associated with subsequent development of a perianal fistula in patients with Crohn's disease.
* indicates p < 0.05; ** Multivariate model includes all significant variables in univariate analysis; Abbreviations: SS = systemic steroids (oral prednisone and IV methylprednisolone, excludes budesonide), IM = immunomodulators
S-253
AGA Abstracts