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763 Outcome of Acute Severe Ulcerative Colitis: Data From the UK National IBD Audit
AGA Abstracts
by patient age and/or the presence of known risk factors (i.e. malignancy, surgery) remains unknown. Such data are needed to inform recommendations for screening and prophylaxis among patients with IBD. Objectives: 1) To determine whether patients with Crohn's disease (CD) and ulcerative colitis (UC) are at increased risk for DVT and PE, as compared to unaffected controls. 2) To determine if this risk varies by patient age and/or the presence of known risk factors. Methods: We conducted a population-based, nested case-control study using administrative data obtained from the Danish National Registry of Patients covering all Danish hospitals. We identified incident cases of DVT and PE, using ICD-8 and ICD-10 codes. For each case, we selected 5 age- and gender-matched controls from within the study population using risk set sampling. We then determined the odds ratios of each outcome and prior history of CD or UC using conditional logistic regression. We also stratified by age group (0-20 years, 21-40 years, 41-60 years, and >60 years), and performed additional analyses restricted to unprovoked DVT and PE (occurring in patients without known malignancy, surgery, fracture, trauma, or pregnancy). Results: The study included 71,367 cases of DVT (351,530 population controls) and 54,018 cases of PE (265,799 controls). CD was positively associated with DVT (OR = 2.0, 95% confidence interval (CI): 1.7-2.4), unprovoked DVT (OR = 2.0, 95% CI: 1.6-2.6), PE (OR = 2.4, 95% CI: 1.9-2.9), and unprovoked PE (OR = 2.6, 95% CI: 1.9-3.6). The risk of each thromboembolic outcome was similar in patients with UC (data not shown). Each of these associations was strongest in children age ≤20 years, and decreased with increasing age. The odds ratios among those ≤20 years of age were 10.0 (95% CI: 3.4-29.3) for DVT, 2.9 (95% CI: 0.7-12.2) for unprovoked DVT, 8.3 (95% CI: 2.01.9-34.9) for PE, and 7.2 (95% CI: 1.2-43.0) for unprovoked PE. Discussion: In this nationwide, population-based study, both CD and UC were positively associated with provoked and unprovoked DVT and PE. The risk in children, as compared to unaffected controls, was higher than in adults. These findings may be used to inform risk-benefit analyses of various screening and prophylaxis regimens for this patient population.
group A infants were less likely to meet their developmental milestones compared to the unexposed group. This was true even after excluding from Group B the 39 women who took immunomodulators. There was no association between drug exposure and rate of any pregnancy complication, low birth weight, cesarean section or NICU stay. There was no difference in rate of congenital malformations (CM) by drug exposure: 5 CM were diagnosed at birth, 17 by one year. Group B infants, excluding 39 who also took Group A drugs, had lower rates of preterm birth than both unexposed and group A infants. Conclusions: Developmental milestones at month 9 were lower in infants exposed to azathioprine/6MP, but not biologics. Among women with IBD, the use of immunomodulators and biologics was not associated with an increase in adverse pregnancy events. Number (%) Developmental milestones by month
* p = 0.04 “ p = 0.06 765 Association Between Compliance and Clinical Recurrence in Patients With Quiescent Ulcerative Colitis Receiving MMX® Mesalamine 2.4g/Day as Maintenance Therapy: Results of the Phase IV Simple Trial Sunanda V. Kane, Dory M. Solomon, Mary Palmen, Karen Barrett Background Standard mesalamine formulations require patients to take multiple tablets, multiple times daily. These regimens are associated with poor patient compliance, which can result in recurrence of active disease. MMX® mesalamine (Shire Pharmaceuticals Inc., USA; MMX, Cosmo Technologies Ltd., Ireland) employs a low pill burden and once-daily (QD) dosing. Strategies in Maintenance for Patients Receiving Long-term Therapy (SIMPLE) was therefore designed to investigate the relationship between compliance and disease recurrence in patients with ulcerative colitis (UC). Methods This phase IV, multi-center, open-label trial was conducted in 52 centers across the USA. Patients with quiescent UC (defined as scores of zero for both rectal bleeding and bowel movements, either at enrollment or after 8 weeks' treatment with MMX mesalamine [2.4-4.8g/day; acute phase]) received MMX mesalamine 2.4g/day QD for 12 months (maintenance phase). The primary endpoint of the study was clinical recurrence (defined as four or more bowel movements per day above the patient's normal frequency and associated with any of the following: urgency, abdominal pain or rectal bleeding) at 6 months; secondary endpoints included clinical recurrence at 12 months, compliance and safety. Compliance was assessed via prescription refill data using the formula: [sum of days' supply dispensed] / [sum of days in all refill intervals] x 100; patients filling <80% of prescriptions were considered to be noncompliant. Results 208 patients entered the 12 month maintenance period; 207 were included in the recurrence analysis. The majority of patients did not experience clinical recurrence at either 6 (77%) or 12 (64%) months. Mean compliance was 87%. Overall, 77% of patients received ≥80% of the study medication and were considered to be compliant up to month 12; at month 6, 79% were compliant. Patients who were noncompliant had greater rates of recurrence at 6 (nominal p=0.0476) and 12 months (nominal p=0.0120) than compliant patients (Table). Conclusions In this study, approximately 80% of patients were compliant with once-daily MMX mesalamine therapy. Furthermore, we observed that UC recurrence rates were lower in compliant patients. These data suggest that clinical outcomes are associated with compliance and therefore choosing medication that enhances compliance may benefit patient remission.
763 Outcome of Acute Severe Ulcerative Colitis: Data From the UK National IBD Audit Ian D. Arnott, Keith Leiper, Calvin Down, Derek Lowe, Jonathan Potter, Jonathan M. Rhodes Introduction: Acute severe ulcerative colitis (UC) is a medical emergency requiring hospitalisation. Approximately one third of patients will not respond to therapy and will need colectomy during the hospital admission. Data examining mortality, efficacy of therapy, treatment selection and outcomes often comes from specialised units with relatively few data examining outcomes in larger less selected populations. The UK National IBD Audit collected data on over 6000 adult patients admitted to UK hospitals with IBD. Aims & Methods: Aims: To assess outcomes for patients with acute severe ulcerative colitis in the 2008 National IBD audit. Methods: All hospitals that admitted IBD patients in the UK were invited to take part. Sites completed a questionnaire detailing service at 1st September 2009. Sites were asked to audit 40 set of case notes of patients that were admitted with IBD between 1/09/07 and 31/08/08. Acute severe UC was defined by the Truelove and Witts criteria. Results: 209 sites submitted data; a 93% participation at Trust/Health board level. Data were collected on 6135 patients (3154 CD and 2981 UC). Of the 2981 patients with UC, there were 863 with acute severe disease (465 males, median age 41 years (interquartile range 28 - 58 years). Inpatient mortality was 1.2% with death being strongly associated with increased age (p<0.001), male sex (p=0.02), C. Diff infection (p<0.04) and if first line medical treatment fails the risk of death increases to 2.8%. 61.1% responded to first line treatment with steroids. Of the 317 who failed treatment with steroids 108 underwent surgery without further medical treatment, 98 were treated with cyclosporine and 52 with infliximab. The response rate to infliximab was higher than that to cyclosporine (75% v 46%, p=0.0009). Overall 163 underwent surgery with a median time to surgery of 10 days (interquartile range 7-14 days). The post operative mortality did not differ between those coming to surgery before and after 7 days following admission. Conclusions: The inpatient mortality of acute severe UC in the UK remains appreciable and strongly associated with age and the presence of C. Diff infection. The risk of death doubles if first line medical therapy fails. In this dataset response rates to infliximab are greater than cyclosporin although the results of ongoing clinical trials will give further data. Effective communication between medical and surgical teams, clear decision making and timely surgery will help keep mortality to a minimum. 764
766
One Year Newborn Outcomes Among Offspring of Women With Inflammatory Bowel Disease: The PIANO Registry Uma Mahadevan, Christopher F. Martin, Robert S. Sandler, Sunanda V. Kane, Marla Dubinsky, James D. Lewis, William J. Sandborn, Bruce E. Sands
The Potential Impact of Laxative use on Stool Form and Frequency in Patients With Slow Transit Constipation Philip G. Dinning, Michael Jones, Linda M. Hunt, David Z. Lubowski, Jamshid S. Kalantar, Ian J. Cook
Introduction: IBD in the mother is associated with higher rates of adverse pregnancy outcomes. However, long-term effects of maternal IBD on childhood growth and development are not known. The aim of this study was to determine the impact of IBD medication exposure in utero on newborn development in the first year of life Methods: We created a prospective cohort of pregnant women at 30 US IBD centers to follow patients through pregnancy and first year of child's life. We ascertained IBD medications and disease activity during gestation, complications of pregnancy and delivery, and developmental indicators in infants. Patients were classified by exposure to two groups of drugs taken between conception and delivery: 6MP/Azathioprine (Group A) and infliximab, adalimumab, certolizumab (Group B). We compared these groups to women who took no medications, or did not take any Group A or B drugs. Developmental milestones achieved by the infant, based on Denver Childhood Developmental Score, were measured by the mother at months 4, 9 and 12. Results: 521 women are enrolled in the study as of 11/24/2009: 353 have completed pregnancy, 339 with live births. There were 79 live births in Group A, 124 in Group B (39 took both Group A and B drugs), and 136 to unexposed mothers. The percent of developmental milestones achieved were calculated at months 4, 9, and 12, controlling for preterm birth. (Table) There was no significant difference among exposure groups except at month 9 -
AGA Abstracts
Hard stools and reduced stool frequency have been suggested as predictors of delayed colonic transit. However, for the most part studies describing such correlation have based patients' stool data upon responses to questionnaires or interviews by doctors. The potential impact of laxative use upon stooling characteristics in constipated patients is rarely commented upon and in many cases patient report what they would be like if they didn't take laxatives. Our Aim, in constipated patients, was to correlate stool form and frequency, in the presence of laxative use, with colonic transit. Methods: 98 patients were referred to tertiary referral centre for inclusion in a clinical trial for the treatment of severe constipation. Each of these patients completed a 3-week stool diary and a colonic transit study measured scintigraphically. On a daily basis the dairy detailed stool frequency and form (Bristol stool scale) and laxative use (type and dose). Stool form was categorised as hard (Type 1 & 2), normal (Type 3,4 & 5) and loose (type 6 & 7). Normal and delayed transit individuals were compared via Kruskal-Wallis test and the comparison repeated controlling for laxative use using analysis of co-variance. Results: Of the 98 patients, only 16 (16%) reported no laxative use, while over half (54/98) reported laxative use >4 days per week. The stool
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by patient age and/or the presence of known risk factors (i.e. malignancy, surgery) remains unknown. Such data are needed to inform recommendations for screening and prophylaxis among patients with IBD. Objectives: 1) To determine whether patients with Crohn's disease (CD) and ulcerative colitis (UC) are at increased risk for DVT and PE, as compared to unaffected controls. 2) To determine if this risk varies by patient age and/or the presence of known risk factors. Methods: We conducted a population-based, nested case-control study using administrative data obtained from the Danish National Registry of Patients covering all Danish hospitals. We identified incident cases of DVT and PE, using ICD-8 and ICD-10 codes. For each case, we selected 5 age- and gender-matched controls from within the study population using risk set sampling. We then determined the odds ratios of each outcome and prior history of CD or UC using conditional logistic regression. We also stratified by age group (0-20 years, 21-40 years, 41-60 years, and >60 years), and performed additional analyses restricted to unprovoked DVT and PE (occurring in patients without known malignancy, surgery, fracture, trauma, or pregnancy). Results: The study included 71,367 cases of DVT (351,530 population controls) and 54,018 cases of PE (265,799 controls). CD was positively associated with DVT (OR = 2.0, 95% confidence interval (CI): 1.7-2.4), unprovoked DVT (OR = 2.0, 95% CI: 1.6-2.6), PE (OR = 2.4, 95% CI: 1.9-2.9), and unprovoked PE (OR = 2.6, 95% CI: 1.9-3.6). The risk of each thromboembolic outcome was similar in patients with UC (data not shown). Each of these associations was strongest in children age ≤20 years, and decreased with increasing age. The odds ratios among those ≤20 years of age were 10.0 (95% CI: 3.4-29.3) for DVT, 2.9 (95% CI: 0.7-12.2) for unprovoked DVT, 8.3 (95% CI: 2.01.9-34.9) for PE, and 7.2 (95% CI: 1.2-43.0) for unprovoked PE. Discussion: In this nationwide, population-based study, both CD and UC were positively associated with provoked and unprovoked DVT and PE. The risk in children, as compared to unaffected controls, was higher than in adults. These findings may be used to inform risk-benefit analyses of various screening and prophylaxis regimens for this patient population.
group A infants were less likely to meet their developmental milestones compared to the unexposed group. This was true even after excluding from Group B the 39 women who took immunomodulators. There was no association between drug exposure and rate of any pregnancy complication, low birth weight, cesarean section or NICU stay. There was no difference in rate of congenital malformations (CM) by drug exposure: 5 CM were diagnosed at birth, 17 by one year. Group B infants, excluding 39 who also took Group A drugs, had lower rates of preterm birth than both unexposed and group A infants. Conclusions: Developmental milestones at month 9 were lower in infants exposed to azathioprine/6MP, but not biologics. Among women with IBD, the use of immunomodulators and biologics was not associated with an increase in adverse pregnancy events. Number (%) Developmental milestones by month
* p = 0.04 “ p = 0.06 765 Association Between Compliance and Clinical Recurrence in Patients With Quiescent Ulcerative Colitis Receiving MMX® Mesalamine 2.4g/Day as Maintenance Therapy: Results of the Phase IV Simple Trial Sunanda V. Kane, Dory M. Solomon, Mary Palmen, Karen Barrett Background Standard mesalamine formulations require patients to take multiple tablets, multiple times daily. These regimens are associated with poor patient compliance, which can result in recurrence of active disease. MMX® mesalamine (Shire Pharmaceuticals Inc., USA; MMX, Cosmo Technologies Ltd., Ireland) employs a low pill burden and once-daily (QD) dosing. Strategies in Maintenance for Patients Receiving Long-term Therapy (SIMPLE) was therefore designed to investigate the relationship between compliance and disease recurrence in patients with ulcerative colitis (UC). Methods This phase IV, multi-center, open-label trial was conducted in 52 centers across the USA. Patients with quiescent UC (defined as scores of zero for both rectal bleeding and bowel movements, either at enrollment or after 8 weeks' treatment with MMX mesalamine [2.4-4.8g/day; acute phase]) received MMX mesalamine 2.4g/day QD for 12 months (maintenance phase). The primary endpoint of the study was clinical recurrence (defined as four or more bowel movements per day above the patient's normal frequency and associated with any of the following: urgency, abdominal pain or rectal bleeding) at 6 months; secondary endpoints included clinical recurrence at 12 months, compliance and safety. Compliance was assessed via prescription refill data using the formula: [sum of days' supply dispensed] / [sum of days in all refill intervals] x 100; patients filling <80% of prescriptions were considered to be noncompliant. Results 208 patients entered the 12 month maintenance period; 207 were included in the recurrence analysis. The majority of patients did not experience clinical recurrence at either 6 (77%) or 12 (64%) months. Mean compliance was 87%. Overall, 77% of patients received ≥80% of the study medication and were considered to be compliant up to month 12; at month 6, 79% were compliant. Patients who were noncompliant had greater rates of recurrence at 6 (nominal p=0.0476) and 12 months (nominal p=0.0120) than compliant patients (Table). Conclusions In this study, approximately 80% of patients were compliant with once-daily MMX mesalamine therapy. Furthermore, we observed that UC recurrence rates were lower in compliant patients. These data suggest that clinical outcomes are associated with compliance and therefore choosing medication that enhances compliance may benefit patient remission.
763 Outcome of Acute Severe Ulcerative Colitis: Data From the UK National IBD Audit Ian D. Arnott, Keith Leiper, Calvin Down, Derek Lowe, Jonathan Potter, Jonathan M. Rhodes Introduction: Acute severe ulcerative colitis (UC) is a medical emergency requiring hospitalisation. Approximately one third of patients will not respond to therapy and will need colectomy during the hospital admission. Data examining mortality, efficacy of therapy, treatment selection and outcomes often comes from specialised units with relatively few data examining outcomes in larger less selected populations. The UK National IBD Audit collected data on over 6000 adult patients admitted to UK hospitals with IBD. Aims & Methods: Aims: To assess outcomes for patients with acute severe ulcerative colitis in the 2008 National IBD audit. Methods: All hospitals that admitted IBD patients in the UK were invited to take part. Sites completed a questionnaire detailing service at 1st September 2009. Sites were asked to audit 40 set of case notes of patients that were admitted with IBD between 1/09/07 and 31/08/08. Acute severe UC was defined by the Truelove and Witts criteria. Results: 209 sites submitted data; a 93% participation at Trust/Health board level. Data were collected on 6135 patients (3154 CD and 2981 UC). Of the 2981 patients with UC, there were 863 with acute severe disease (465 males, median age 41 years (interquartile range 28 - 58 years). Inpatient mortality was 1.2% with death being strongly associated with increased age (p<0.001), male sex (p=0.02), C. Diff infection (p<0.04) and if first line medical treatment fails the risk of death increases to 2.8%. 61.1% responded to first line treatment with steroids. Of the 317 who failed treatment with steroids 108 underwent surgery without further medical treatment, 98 were treated with cyclosporine and 52 with infliximab. The response rate to infliximab was higher than that to cyclosporine (75% v 46%, p=0.0009). Overall 163 underwent surgery with a median time to surgery of 10 days (interquartile range 7-14 days). The post operative mortality did not differ between those coming to surgery before and after 7 days following admission. Conclusions: The inpatient mortality of acute severe UC in the UK remains appreciable and strongly associated with age and the presence of C. Diff infection. The risk of death doubles if first line medical therapy fails. In this dataset response rates to infliximab are greater than cyclosporin although the results of ongoing clinical trials will give further data. Effective communication between medical and surgical teams, clear decision making and timely surgery will help keep mortality to a minimum. 764
766
One Year Newborn Outcomes Among Offspring of Women With Inflammatory Bowel Disease: The PIANO Registry Uma Mahadevan, Christopher F. Martin, Robert S. Sandler, Sunanda V. Kane, Marla Dubinsky, James D. Lewis, William J. Sandborn, Bruce E. Sands
The Potential Impact of Laxative use on Stool Form and Frequency in Patients With Slow Transit Constipation Philip G. Dinning, Michael Jones, Linda M. Hunt, David Z. Lubowski, Jamshid S. Kalantar, Ian J. Cook
Introduction: IBD in the mother is associated with higher rates of adverse pregnancy outcomes. However, long-term effects of maternal IBD on childhood growth and development are not known. The aim of this study was to determine the impact of IBD medication exposure in utero on newborn development in the first year of life Methods: We created a prospective cohort of pregnant women at 30 US IBD centers to follow patients through pregnancy and first year of child's life. We ascertained IBD medications and disease activity during gestation, complications of pregnancy and delivery, and developmental indicators in infants. Patients were classified by exposure to two groups of drugs taken between conception and delivery: 6MP/Azathioprine (Group A) and infliximab, adalimumab, certolizumab (Group B). We compared these groups to women who took no medications, or did not take any Group A or B drugs. Developmental milestones achieved by the infant, based on Denver Childhood Developmental Score, were measured by the mother at months 4, 9 and 12. Results: 521 women are enrolled in the study as of 11/24/2009: 353 have completed pregnancy, 339 with live births. There were 79 live births in Group A, 124 in Group B (39 took both Group A and B drugs), and 136 to unexposed mothers. The percent of developmental milestones achieved were calculated at months 4, 9, and 12, controlling for preterm birth. (Table) There was no significant difference among exposure groups except at month 9 -
AGA Abstracts
Hard stools and reduced stool frequency have been suggested as predictors of delayed colonic transit. However, for the most part studies describing such correlation have based patients' stool data upon responses to questionnaires or interviews by doctors. The potential impact of laxative use upon stooling characteristics in constipated patients is rarely commented upon and in many cases patient report what they would be like if they didn't take laxatives. Our Aim, in constipated patients, was to correlate stool form and frequency, in the presence of laxative use, with colonic transit. Methods: 98 patients were referred to tertiary referral centre for inclusion in a clinical trial for the treatment of severe constipation. Each of these patients completed a 3-week stool diary and a colonic transit study measured scintigraphically. On a daily basis the dairy detailed stool frequency and form (Bristol stool scale) and laxative use (type and dose). Stool form was categorised as hard (Type 1 & 2), normal (Type 3,4 & 5) and loose (type 6 & 7). Normal and delayed transit individuals were compared via Kruskal-Wallis test and the comparison repeated controlling for laxative use using analysis of co-variance. Results: Of the 98 patients, only 16 (16%) reported no laxative use, while over half (54/98) reported laxative use >4 days per week. The stool
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