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Sa1182 Single-Center Experience of Vedolizumab in Patients With Inflammatory Bowel Disease: Does Age Matter?
AGA Abstracts
Sa1182
Sa1183
Single-Center Experience of Vedolizumab in Patients With Inflammatory Bowel Disease: Does Age Matter? Bradley Morganstern, Namita Singh, Stephan Targan, Carol J. Landers, Minh Nguyen, Eric A. Vasiliauskas, David Shih, Edward J. Feldman, Andrew Ippoliti, Dermot McGovern, Marla Dubinsky, Shervin Rabizadeh, Gil Y. Melmed
Adverse Events to Thiopurines Can Be Overcome and the Majority of Patients Respond to Therapy - Clinical Outcomes From the EATME Study Antony Friedman, John D. Brookes, Mark G. Ward, Belinda Headon, Lucy N. Nihill, John Reynolds, Miles Sparrow, Peter R. Gibson Background: Thiopurines [azathioprine (AZA) and mercaptopurine (MP)] are the mainstay of IBD treatment. There is poor correlation between standard weight-based dosing and the levels of thiopurine metabolites: the efficacious 6-thioguianine nucleotides (6TGN) and the toxic 6-methylmercaptopurine (6MMP). 15% of patients are "thiopurine shunters" with 6MMP:6TGN ratio ‡20. Patients start on a low dose and gradually escalate to full dose to avoid non-specific adverse events (AEs). AE rates leading to drug cessation are up to 40% and response rates are as low as 40%. Aims: to prospectively determine that: (a) AEs and inefficacy can be overcome by switching thiopurines and/or adding low-dose allopurinol; (b) these strategies significantly improve real-world outcomes of patients on thiopurines. Methods: Single centre, prospective, open label study of consecutive IBD patients commencing thiopurines. Patients were commenced on 50 mg AZA or 25 mg MP. Doses increased fortnightly by 50mg for AZA or 25mg for MP until target dose was achieved, aiming for 22.5mg/kg for AZA and 1-1.5mg/kg for MP, with fortnightly monitoring of hematology, CRP and liver function. Thiopurine metabolites were considered in clinical decision-making once steady-state was achieved. If a patient developed an AE requiring drug cessation, one or more of the following interventions were used: switching to the other thiopurine, addition of allopurinol with dose-reduced thiopurine, or use of thioguanine. Clinical and biochemical outcomes were recorded. Mixed model analyses were performed to estimate means and standard errors. McNemar's test was used to assess achievement of clinical remission. Results: 64 patients were enrolled. 52 patients (81%) had Crohn's disease (CD), 11 (17%) ulcerative colitis (UC) and 1 (2%) IBD-U. 42 were commenced on AZA and 22 MP (decision at physician discretion). 39 (61%) achieved full dose of their first thiopurine. AZA tended to have a better AE profile than MP, with 21% vs 41% requiring drug cessation (p=0.10). Of those with AEs, 14 (22%) tolerated allopurinol/thiopurine combination, 3 (5%) tolerated the other thiopurine and 1 (2%) tolerated thioguanine. Overall, this allowed an additional 28% of patients to tolerate thiopurines. 10 (16%) could not tolerate thiopurines despite these optimisation measures, 7 (11%) were non-compliant and 4 (6%) were lost to follow up. 23% of MP and 14% of AZA patients were shunters (p=0.395). Patients tolerating thiopurines had significant improvements in disease activity with 71% of CD patients achieving remission via Harvey-Bradshaw Index, (p=0.001) and 75% with UC via the Simple Clinical Colitis Activity Index (p=0.06). Conclusions: Thiopurine manipulation allows the majority of patients to tolerate and respond to thiopurines. AZA seems to have a better AE profile than MP and could be considered first line therapy.
Background: Vedolizumab, an anti-a4b7 integrin which inhibits lymphocyte migration to the gastrointestinal tract, was recently approved in the United States for the treatment of ulcerative colitis (UC) and Crohn's disease (CD). The study aims were to describe the safety and efficacy of vedolizumab in adult patients at a tertiary care IBD center and to determine predictors of vedolizumab efficacy. Methods: IBD patients 18 years or older treated with vedolizumab from June through November 2014 were assessed for safety and response to treatment. Laboratory and clinical data (demographics, surgical history, disease behavior, location of disease, prior medications, C-reactive protein (CRP)) along with IBD-associated serologies (p-ANCA) were assessed at baseline. The primary measure of response was a 50% reduction in CRP. Other measures of disease activity included the physician global assessment (PGA) (0=remission, 1=mild, 2=moderate, 3=severe), CRP at week 6 and week 14 infusions. Descriptive statistics and univariate analyses were used to compare differences in outcomes based on clinical and serologic factors. Results: 66 patients received vedolizumab; median age at diagnosis was 19 (range 7-72) years and median disease duration of 8.6 (range 155) years. Median CRP at baseline was 0.4 (IQR 0.12-1.64) mg/dL. Seven patients (11%) switched from natalizumab. Twenty-two patients (37%) were on a concomitant immunomodulator (IMM) at their first infusion. Only 5 patients (8%) were anti-TNF naive and 20 patients (32%) received one prior anti-TNF agent, 38 patients (61%) received two or more prior anti-TNF agents (median 2). Seven patients switched from natalizumab. Of the 37 patients with available serologic data, 13 (35%) had elevated p-ANCA. At weeks 6 and 14, 49% and 42% of patients respectively, had a decrease in CRP by at least 50%. In patients starting therapy with active disease (abnormal CRP or elevated PGA), responders were significantly older both at week 6 (mean age 42.5 vs. 25.5 years, p=0.01) and at week 14 (mean age 43.6 vs. 20.9 years, p=0.02). No differences in response were seen when patients were compared by disease type (CD vs UC), IMM use, prior natalizumab, time from last anti-TNF agent, prior anti-TNF exposure and p-ANCA elevation. Vedolizumab was generally well tolerated; 15% had transient transaminitis (<2x normal). Two patients discontinued therapy due to headaches/insomnia or musculoskeletal pain. One patient on concomitant corticosteroids developed herpes zoster. Conclusion: Early experience with vedolizumab at a tertiary care center demonstrates clinical efficacy, and appears to be well tolerated. Older age may correlate with a higher likelihood of response. Further experience with vedolizumab is needed to help understand which clinical and serologic factors predict response. Results
Sa1184 The Role of Faecal S100A12 in Monitoring Disease Activity and Predicting Relapses in Paediatric Inflammatory Bowel Disease Andrew S. Day, Annemieke M. Peters van Ton, Laura Burgess, Richard B. Gearry Aim: The ability to predict the risk of relapse in children with inflammatory bowel disease (IBD) would enable optimisation and personalisation of therapy. Faecal S100A12 concentrations correlate closely with the presence of gut inflammation. Recent work indicates that this biomarker provides an indication of possible future relapse. The aim of this study was to establish the predictive value of S100A12 in a large prospective paediatric cohort with known IBD. Methods: All children were followed prospectively with serial assessment of disease activity (using established activity indices), serum inflammatory markers and growth. Serial stool samples were used to measure faecal S100A12 using an established enzymelinked immunoassay. Results: Fifty-eight children with a confirmed diagnosis of IBD were recruited: 49 (85%) of the children were diagnosed with Crohn disease: the remainder had ulcerative colitis or IBD unclassified. These children had a mean age of 11.9 years and had been diagnosed for a median of 1.6 years. Thirty children were in remission at baseline, whilst seven had moderate/severe activity. Faecal S100A12 levels were higher with colonic involvement (p=0.03) and varied with disease activity (p=0.002). S100A12 levels also correlated with serum inflammatory markers and weight and height Z-scores. A trend towards a significant correlation was seen with S100A12 and endoscopic severity in children with Crohn's disease. A baseline faecal S100A12 concentration >10mg/kg was associated with an increased risk of clinical relapse in the following 12 months (HR 4.1 (95% CI: 1.1-14.4), p=0.03). A cut-off of 11.47 mg/kg resulted in sensitivity and specificity of 83% and 57%, respectively, for relapse prediction in the following 12 months. Conclusions: Measurement of faecal S100A12 concentration may assist in predicting the risk of future clinical relapse in children with IBD and provide opportunities for optimisation of therapy. Further studies in a larger group of children are now required before this biomarker can be considered for implementation in clinical practice.
IQR: interquartile range; CRP: C-reactive protein; ESR: erythrocyte sedimentation rate
Sa1185 Safety and Long Term Outcome of Primary Ileocecal Resection for Terminal Ileal Crohn's Disease: A Multicenter Large Cohort Analysis Anthony de Buck van Overstraeten, Emma J. Eshuis, Severine Vermeire, Gert A. Van Assche, Marc Ferrante, Geert R. D'Haens, Cyriel Ponsioen, Albert M. Wolthuis, Willem A. Bemelman, Andre D'Hoore
Baseline Demographics of Patients Starting Vedolizumab
Introduction: Despite improvement of medical therapy, majority of patients will require surgical resection at some stage of their disease. In previous series surgical recurrence has been noted between 30 and 60%. Aim: To report current safety and long-term clinical and surgical recurrence after ileocecal Crohn's disease in a large multicenter cohort and describe predictors for recurrence. Methods: A prospective cohort analysis of all patients undergoing surgery for ileocecal Crohn's in two academic centers was performed. Anastomotic leakage and risk factors were assessed. Kaplan-meier estimates were used to describe long-term clinical and surgical recurrence. Risk factors for both endpoints were identified. Results: 538 patients underwent a primary ileocecal resection between 1998 and 2013 (male: n=
AGA Abstracts
S-250
Sa1182
Sa1183
Single-Center Experience of Vedolizumab in Patients With Inflammatory Bowel Disease: Does Age Matter? Bradley Morganstern, Namita Singh, Stephan Targan, Carol J. Landers, Minh Nguyen, Eric A. Vasiliauskas, David Shih, Edward J. Feldman, Andrew Ippoliti, Dermot McGovern, Marla Dubinsky, Shervin Rabizadeh, Gil Y. Melmed
Adverse Events to Thiopurines Can Be Overcome and the Majority of Patients Respond to Therapy - Clinical Outcomes From the EATME Study Antony Friedman, John D. Brookes, Mark G. Ward, Belinda Headon, Lucy N. Nihill, John Reynolds, Miles Sparrow, Peter R. Gibson Background: Thiopurines [azathioprine (AZA) and mercaptopurine (MP)] are the mainstay of IBD treatment. There is poor correlation between standard weight-based dosing and the levels of thiopurine metabolites: the efficacious 6-thioguianine nucleotides (6TGN) and the toxic 6-methylmercaptopurine (6MMP). 15% of patients are "thiopurine shunters" with 6MMP:6TGN ratio ‡20. Patients start on a low dose and gradually escalate to full dose to avoid non-specific adverse events (AEs). AE rates leading to drug cessation are up to 40% and response rates are as low as 40%. Aims: to prospectively determine that: (a) AEs and inefficacy can be overcome by switching thiopurines and/or adding low-dose allopurinol; (b) these strategies significantly improve real-world outcomes of patients on thiopurines. Methods: Single centre, prospective, open label study of consecutive IBD patients commencing thiopurines. Patients were commenced on 50 mg AZA or 25 mg MP. Doses increased fortnightly by 50mg for AZA or 25mg for MP until target dose was achieved, aiming for 22.5mg/kg for AZA and 1-1.5mg/kg for MP, with fortnightly monitoring of hematology, CRP and liver function. Thiopurine metabolites were considered in clinical decision-making once steady-state was achieved. If a patient developed an AE requiring drug cessation, one or more of the following interventions were used: switching to the other thiopurine, addition of allopurinol with dose-reduced thiopurine, or use of thioguanine. Clinical and biochemical outcomes were recorded. Mixed model analyses were performed to estimate means and standard errors. McNemar's test was used to assess achievement of clinical remission. Results: 64 patients were enrolled. 52 patients (81%) had Crohn's disease (CD), 11 (17%) ulcerative colitis (UC) and 1 (2%) IBD-U. 42 were commenced on AZA and 22 MP (decision at physician discretion). 39 (61%) achieved full dose of their first thiopurine. AZA tended to have a better AE profile than MP, with 21% vs 41% requiring drug cessation (p=0.10). Of those with AEs, 14 (22%) tolerated allopurinol/thiopurine combination, 3 (5%) tolerated the other thiopurine and 1 (2%) tolerated thioguanine. Overall, this allowed an additional 28% of patients to tolerate thiopurines. 10 (16%) could not tolerate thiopurines despite these optimisation measures, 7 (11%) were non-compliant and 4 (6%) were lost to follow up. 23% of MP and 14% of AZA patients were shunters (p=0.395). Patients tolerating thiopurines had significant improvements in disease activity with 71% of CD patients achieving remission via Harvey-Bradshaw Index, (p=0.001) and 75% with UC via the Simple Clinical Colitis Activity Index (p=0.06). Conclusions: Thiopurine manipulation allows the majority of patients to tolerate and respond to thiopurines. AZA seems to have a better AE profile than MP and could be considered first line therapy.
Background: Vedolizumab, an anti-a4b7 integrin which inhibits lymphocyte migration to the gastrointestinal tract, was recently approved in the United States for the treatment of ulcerative colitis (UC) and Crohn's disease (CD). The study aims were to describe the safety and efficacy of vedolizumab in adult patients at a tertiary care IBD center and to determine predictors of vedolizumab efficacy. Methods: IBD patients 18 years or older treated with vedolizumab from June through November 2014 were assessed for safety and response to treatment. Laboratory and clinical data (demographics, surgical history, disease behavior, location of disease, prior medications, C-reactive protein (CRP)) along with IBD-associated serologies (p-ANCA) were assessed at baseline. The primary measure of response was a 50% reduction in CRP. Other measures of disease activity included the physician global assessment (PGA) (0=remission, 1=mild, 2=moderate, 3=severe), CRP at week 6 and week 14 infusions. Descriptive statistics and univariate analyses were used to compare differences in outcomes based on clinical and serologic factors. Results: 66 patients received vedolizumab; median age at diagnosis was 19 (range 7-72) years and median disease duration of 8.6 (range 155) years. Median CRP at baseline was 0.4 (IQR 0.12-1.64) mg/dL. Seven patients (11%) switched from natalizumab. Twenty-two patients (37%) were on a concomitant immunomodulator (IMM) at their first infusion. Only 5 patients (8%) were anti-TNF naive and 20 patients (32%) received one prior anti-TNF agent, 38 patients (61%) received two or more prior anti-TNF agents (median 2). Seven patients switched from natalizumab. Of the 37 patients with available serologic data, 13 (35%) had elevated p-ANCA. At weeks 6 and 14, 49% and 42% of patients respectively, had a decrease in CRP by at least 50%. In patients starting therapy with active disease (abnormal CRP or elevated PGA), responders were significantly older both at week 6 (mean age 42.5 vs. 25.5 years, p=0.01) and at week 14 (mean age 43.6 vs. 20.9 years, p=0.02). No differences in response were seen when patients were compared by disease type (CD vs UC), IMM use, prior natalizumab, time from last anti-TNF agent, prior anti-TNF exposure and p-ANCA elevation. Vedolizumab was generally well tolerated; 15% had transient transaminitis (<2x normal). Two patients discontinued therapy due to headaches/insomnia or musculoskeletal pain. One patient on concomitant corticosteroids developed herpes zoster. Conclusion: Early experience with vedolizumab at a tertiary care center demonstrates clinical efficacy, and appears to be well tolerated. Older age may correlate with a higher likelihood of response. Further experience with vedolizumab is needed to help understand which clinical and serologic factors predict response. Results
Sa1184 The Role of Faecal S100A12 in Monitoring Disease Activity and Predicting Relapses in Paediatric Inflammatory Bowel Disease Andrew S. Day, Annemieke M. Peters van Ton, Laura Burgess, Richard B. Gearry Aim: The ability to predict the risk of relapse in children with inflammatory bowel disease (IBD) would enable optimisation and personalisation of therapy. Faecal S100A12 concentrations correlate closely with the presence of gut inflammation. Recent work indicates that this biomarker provides an indication of possible future relapse. The aim of this study was to establish the predictive value of S100A12 in a large prospective paediatric cohort with known IBD. Methods: All children were followed prospectively with serial assessment of disease activity (using established activity indices), serum inflammatory markers and growth. Serial stool samples were used to measure faecal S100A12 using an established enzymelinked immunoassay. Results: Fifty-eight children with a confirmed diagnosis of IBD were recruited: 49 (85%) of the children were diagnosed with Crohn disease: the remainder had ulcerative colitis or IBD unclassified. These children had a mean age of 11.9 years and had been diagnosed for a median of 1.6 years. Thirty children were in remission at baseline, whilst seven had moderate/severe activity. Faecal S100A12 levels were higher with colonic involvement (p=0.03) and varied with disease activity (p=0.002). S100A12 levels also correlated with serum inflammatory markers and weight and height Z-scores. A trend towards a significant correlation was seen with S100A12 and endoscopic severity in children with Crohn's disease. A baseline faecal S100A12 concentration >10mg/kg was associated with an increased risk of clinical relapse in the following 12 months (HR 4.1 (95% CI: 1.1-14.4), p=0.03). A cut-off of 11.47 mg/kg resulted in sensitivity and specificity of 83% and 57%, respectively, for relapse prediction in the following 12 months. Conclusions: Measurement of faecal S100A12 concentration may assist in predicting the risk of future clinical relapse in children with IBD and provide opportunities for optimisation of therapy. Further studies in a larger group of children are now required before this biomarker can be considered for implementation in clinical practice.
IQR: interquartile range; CRP: C-reactive protein; ESR: erythrocyte sedimentation rate
Sa1185 Safety and Long Term Outcome of Primary Ileocecal Resection for Terminal Ileal Crohn's Disease: A Multicenter Large Cohort Analysis Anthony de Buck van Overstraeten, Emma J. Eshuis, Severine Vermeire, Gert A. Van Assche, Marc Ferrante, Geert R. D'Haens, Cyriel Ponsioen, Albert M. Wolthuis, Willem A. Bemelman, Andre D'Hoore
Baseline Demographics of Patients Starting Vedolizumab
Introduction: Despite improvement of medical therapy, majority of patients will require surgical resection at some stage of their disease. In previous series surgical recurrence has been noted between 30 and 60%. Aim: To report current safety and long-term clinical and surgical recurrence after ileocecal Crohn's disease in a large multicenter cohort and describe predictors for recurrence. Methods: A prospective cohort analysis of all patients undergoing surgery for ileocecal Crohn's in two academic centers was performed. Anastomotic leakage and risk factors were assessed. Kaplan-meier estimates were used to describe long-term clinical and surgical recurrence. Risk factors for both endpoints were identified. Results: 538 patients underwent a primary ileocecal resection between 1998 and 2013 (male: n=
AGA Abstracts
S-250