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S1099 Systemic AA Amyloidosis in Crohn's Disease (CD): A Serum Amyloid P Component (SAP) Scintigraphy Study
AGA Abstracts
assess whether IS discontinuation in patients in remission with combination therapy influences disease outcome and particularly IFX failure. Patients and methods: Among the 5120 patients with CD or UC evaluated in our tertiary center, medical files from 96 patients with controlled disease after having started IFX combined with IS (purine analog or methotrexate) and who subsequently interrupt IS were retrospectively analyzed. Clinical and follow up data were compared to those of a control group composed of 22 patients with CD or UC still on combination therapy (IFX and IS) after 14 months (corresponding to the median duration of combination therapy in the study group) and who did not interrupt IS. Disease recurrence was defined as the reappearance of clinical manifestations requiring shortening of the dosing interval or increasing the IFX dose to 10 mg/kg. IFX failure was defined as a requirement of surgery, corticosteroid treatment or switch to adalimumab (allergy reaction excluded). Statistical analysis evaluated the relapse and IFX failure free survival rate (KaplanMeier method, log rank test). Results: Both patients groups were similar concerning gender, IBD type, phenotype and topography, age at IS and IFX onset and smoking habits. Patients of both IS withdrawal and combination therapy groups had a similar recurrence rate (38.8%; IC95% [28.1% - 50.8%] vs 40.6%; IC95% [21.1% - 63.6%]; p=0.80) and a similar IFX failure rate (12.5%; IC95% [6.6% - 22.4%] vs 6.2%; IC95% [1.0% - 30.5%]; p=0.57) at one year. In the IS withdrawal group, several factors, namely, sex, IBD type, phenotype and topography, age at diagnosis, smoking habits, past surgery, IS type and CRP, platelet count, neutrophil count at the time of IS withdrawal entered an analysis looking for factors associated with recurrence or IFX failure. None of these factors was associated with recurrence or IFX failure. Conclusion: IS withdrawal in patients with scheduled IFX maintenance therapy for IBD do not increase disease recurrence rate or IFX failure rate. No predictive factors of disease recurrence or IFX failure after IS withdrawal could be pointed out. These data favour IS withdrawal strategy in patients with scheduled IFX maintenance therapy. Référence: (1) Van Assche et al. Gastroenterology 2008
or IgA. Two weeks postoperatively a decrease in serum levels of ASCA IgG (p = 0.03) and an increase in ASCA IgA (p = 0.01) could be detected. These returned to pre-operative levels by month 4 and significant changes in serum ASCA titers could not be detected, neither during the 12 months follow-up (n=60) nor during further follow-up (median 101 month, range 90 - 180 months) in 41 patients. Surgical recurrence occurred in 9/41 patients (22%) with follow-up beyond 12 months. Baseline ASCA IgA and IgG antibody response was neither qualitatively nor quantitatively a predictor of risk for re-operation (p>0.05). Conclusions: ASCA serum titers remain reliably stable even after curative intestinal resection. Our data suggest that ASCA as stand alone serologic marker appears not helpful to predict surgical recurrence in an adult cohort of patients with CD. S1098 Patient Preferences for Crohn's Disease: A Discrete Choice Experiment in Flare-Up and Maintenance Therapy Xavier Calvet, Carlos Taxonera, Elena Ricart, Daniel Ginard, Antonio López-San Román, Javier P. Gisbert, Francesc Casellas, Josep Darbá, Gabriela Restovic, Francisco Javier Sabater OBJECTIVE: To identify patient preferences regarding various aspects of Crohn's disease (CD) flare-up and maintenance therapy for CD patients in Spain. METHODS: The main attributes of CD flare-up or maintenance treatment were determined from a review of the literature and consultations with medical experts and patients. The discrete choice experiment included the following attributes: type of drug administration, disease control, mild-tomoderate adverse events, aesthetic adverse events, serious adverse events and tumor incidence, plus a cost attribute in order to estimate willingness to pay (WTP) for improvements in attribute levels. One hundred sixty-eight patients filled the questionnaire for flare-up therapy and 208 patients the one for maintenance therapy for CD. They were presented with pairs of hypothetical treatment profiles with varied levels of adverse events, disease control, type of administration, tumor incidence and cost. Questions were also included to collect socio-demographic data. Data were analyzed using a random effects probit model. RESULTS: All attributes had the expected polarity and all were significant predictors of choice, except for mild-to-moderate adverse events, which was excluded from both analyses. Patients in flare-up therapy were WTP €144.4/month for a 10% reduction in the probability of experiencing serious adverse events. WTP for a similar reduction in aesthetic adverse events was €5.5/month, and €13.5/month for a 1% increase in the probability of obtaining a clinical response. In the maintenance therapy setting, patients were WTP €1112.4/month for a 1% reduction in the probability of presenting a tumor, €22.7/month for a 1% reduction in the rate of serious adverse events; and €21.1/month for a 1% increase in the probability of obtaining a clinical response. Patients were also willing to pay €276/month and €223/ month to have their treatment administered orally rather than with an injection or an infusion respectively. CONCLUSION: Spanish CD patients have well-defined preferences among treatment attributes and are willing to accept trade-offs. Patients in flare-up therapy indicated that they were willing to accept a high risk of aesthetic adverse events in exchange for clinical efficacy, but only a low risk of serious adverse events. Patients in maintenance therapy were willing to accept quite a high risk of serious adverse events, but only a low risk of neoplasia, in exchange for clinical efficacy. We conclude that patients' perspectives should be taken into account when treatment decisions are taken.
S1096 Pre-Operative Infliximab Exposure and the Occurrence of Post-Operative Complications Following Proctocolectomy and Ileal Pouch-Anal Anastomosis (IPAA) for Ulcerative Colitis (UC) Jason M. Swoger, Edward V. Loftus, Darrell S. Pardi, Sunanda V. Kane, William J. Tremaine, William A. Faubion, David H. Bruining, Eric J. Dozois, John H. Pemberton, Bruce G. Wolff, David W. Larson, Robert R. Cima, Prabin Thapa, William S. Harmsen, Alan R. Zinsmeister, William J. Sandborn Background: IPAA is the surgical procedure of choice for patients (pts) with UC. Many pts receive pre-operative therapy (rx) with an anti-tumor necrosis factor (TNF) antibody. Conflicting data exist regarding the effect of pre-operative anti-TNF rx on post-operative complications. Aims: To describe the association between pre-operative anti-TNF rx and post-operative complications in pts undergoing IPAA for UC. Methods: Pts who underwent IPAA for UC at our institution between 2002-07 were identified. A retrospective chart review was performed. Endpoints were occurrence of any complication, early (<30 d) and late (<6 mo), and early septic complications. Logistic regression, Cox proportional hazard regression, and Poisson regression assessed variables associated with these outcomes. Results: A total of 436 pts underwent IPAA during the study period. Median age at surgery was 38.4 years; 59% were male. Twenty-five percent received anti-TNF rx prior to colectomy, including 64 pts (15%) within 12 weeks of surgery (current). Forty-three percent were receiving immunomodulators and 64% were receiving corticosteroids at surgery. Three hundredfourteen pts (72%) experienced 584 overall complications. Univariate logistic regression showed no significant association between current anti-TNF rx and early complications (OR, 0.8; 95% CI, 0.5-1.4), including septic complications (OR, 1.3; 95% CI, 0.7-2.4). Disease activity, current steroid rx, and number of immunosuppressant medications were not significantly associated with early complications. In a multi-variable model, current anti-TNF rx (relative to none) was associated with early septic complications (OR, 2.5; 95% CI, 1.06.1). Fulminant disease activity (relative to low) and increased BMI were also significantly associated with early infectious complications. A 3-stage surgery was associated with a lower odds of an early infectious complication compared to a 2-stage surgery. A Poisson regression model indicated significant associations for fulminant disease activity (relative to low) with an increased number of early and late complications, and 3-stage surgery (relative to 2stage) with fewer early and late complications. Conclusions: Pre-operative exposure to antiTNF rx may be associated with an increased risk of early infectious complications following colectomy, but not overall early or late complications in UC pts following IPAA. Performing a 3-stage surgery in pre-selected high risk pts is associated with fewer early infectious and overall early and late complications than with a 2-stage surgery.
S1099 Systemic AA Amyloidosis in Crohn's Disease (CD): A Serum Amyloid P Component (SAP) Scintigraphy Study Prayman Sattianayagam, Simon D. Gibbs, Ashutosh Wechalekar, Janet A. Gilbertson, Helen J. Lachmann, Hawkins N. Philip, Julian D. Gillmore Introduction : CD is a recognised cause of AA amyloidosis (AAA), which is characterised by deposition of protein in a fibrillary conformation and consequent organ dysfunction. The AA fibril precursor protein is the acute phase reactant serum amyloid A protein (SAA), which is synthesized in the liver. Amyloid regression and improvement in amyloidotic organ function can occur with reduction of inflammation, in particular SAA concentration. Aims and Methods : To report the natural history and outcome of AAA secondary to CD, as assessed by SAP scintigraphy (a method of serially quantifying whole body amyloid load), and serial SAA (normal 3mg/l) and C-reactive protein (CRP) (normal <0.8mg/l) levels. A review of all AAA cases secondary to CD seen at our institution over a 20 year period (19892008) was undertaken. Results :19 cases (12 male) were identified. Median age at diagnosis of AAA was 37 (range 22-67) and median length of follow-up (FU) was 3.6 years (range 0.2-18). A proteinuric renal presentation was universal and amyloid cardiomyopathy did not occur in any patient during FU. Median time from diagnosis of CD to features of renal dysfunction was 16 years (range 0.1-32). Median time from renal dysfunction to end-stage renal failure (ESRF) in 12 cases was 2 years (range 0.1-9 years). At baseline, splenic, adrenal and hepatic amyloid deposits were present on SAP scintigraphy in 19, 10 and 1 case respectively. Proteinuria completely resolved and renal excretory function remained stable in the only patient whose median SAA remained completely normal throughout 9.5 years of FU. Despite normal CRP levels in 2 patients, amyloid did not regress and renal function did not improve; however, serial SAA measurements of 12 and 16 mg/l indicated ongoing inflammation. Renal transplantation (RTx) was undertaken in 5 cases a median of 1 year (range 0.2-7.3) from ESRF. Median graft survival at censor was 14.5 years (range 1.6-23). Graft failure due to amyloid recurrence occurred in 1 case whose median SAA after RTx was 16.5 mg/l. Despite SAP scan evidence of graft amyloid within 8 years of RTx, this graft survived 14.5 years. Median SAA in each of 4 patients whose amyloid did not recur after RTx was <5 mg/l. Conclusions : AAA in CD presents with proteinuria, typically in the nephrotic range. Cases of CD should be screened for AAA with regular urine dipstick testing. Good control of the underlying inflammation (guided by SAA rather than CRP levels) can result in stabilisation or regression of amyloid and improvement in organ function. RTx is recommended in selected cases of CD-associated AAA provided that inflammation is controlled.
S1097 Impact of Intestinal Resection On and Prognostic Value of Anti-Saccharomyces Cerevisiae Serology in Patients with Crohn's Disease During Long-Term Follow-Up Alexander Eser, Pavol Papay, Wolfgang Miehsler, Clemens Dejaco, Alfred Gangl, Harald Vogelsang, Walter Reinisch Background and objectives: Up to 70 % of patients with Crohn's disease (CD) have to undergo intestinal surgery within 15 years after diagnosis. Serologic markers including antibodies towards Saccharomyces cerevisiae were indicated as predictors of a worse natural course of CD. Here we aimed to investigate the impact of intestinal resection on serum levels of ASCA and the prognostic value of the latter for surgical recurrence during long-term follow-up. Methods: 60 patients undergoing surgery due to stricturing and/or penetrating complications were assayed at time of event, and during postoperative follow up. Serum samples were obtained at baseline (immediately prior to surgery), and after intestinal resection at week 2, months 4, 8, and 12, and thereafter at time of clinic consultation. Data on disease phenotype, surgical recurrence and medication were collected. ASCA titers were determined by ASCA IgG and IgA enzyme-linked immunosorbent assay (QUANTA Lite™ INOVA Diagnostics, Inc., San Diego, California, USA). Results: At baseline 48/60 (80%) of patients were rated as positive for ASCA IgG (median level 42.65 IU, range 3.4 - 655 IU), 46/60 (77%) for ASCA IgA (38.75 IU, 4.1 - 3686 IU) and 52/60 (87%) as positive for either IgG
AGA Abstracts
A-188
assess whether IS discontinuation in patients in remission with combination therapy influences disease outcome and particularly IFX failure. Patients and methods: Among the 5120 patients with CD or UC evaluated in our tertiary center, medical files from 96 patients with controlled disease after having started IFX combined with IS (purine analog or methotrexate) and who subsequently interrupt IS were retrospectively analyzed. Clinical and follow up data were compared to those of a control group composed of 22 patients with CD or UC still on combination therapy (IFX and IS) after 14 months (corresponding to the median duration of combination therapy in the study group) and who did not interrupt IS. Disease recurrence was defined as the reappearance of clinical manifestations requiring shortening of the dosing interval or increasing the IFX dose to 10 mg/kg. IFX failure was defined as a requirement of surgery, corticosteroid treatment or switch to adalimumab (allergy reaction excluded). Statistical analysis evaluated the relapse and IFX failure free survival rate (KaplanMeier method, log rank test). Results: Both patients groups were similar concerning gender, IBD type, phenotype and topography, age at IS and IFX onset and smoking habits. Patients of both IS withdrawal and combination therapy groups had a similar recurrence rate (38.8%; IC95% [28.1% - 50.8%] vs 40.6%; IC95% [21.1% - 63.6%]; p=0.80) and a similar IFX failure rate (12.5%; IC95% [6.6% - 22.4%] vs 6.2%; IC95% [1.0% - 30.5%]; p=0.57) at one year. In the IS withdrawal group, several factors, namely, sex, IBD type, phenotype and topography, age at diagnosis, smoking habits, past surgery, IS type and CRP, platelet count, neutrophil count at the time of IS withdrawal entered an analysis looking for factors associated with recurrence or IFX failure. None of these factors was associated with recurrence or IFX failure. Conclusion: IS withdrawal in patients with scheduled IFX maintenance therapy for IBD do not increase disease recurrence rate or IFX failure rate. No predictive factors of disease recurrence or IFX failure after IS withdrawal could be pointed out. These data favour IS withdrawal strategy in patients with scheduled IFX maintenance therapy. Référence: (1) Van Assche et al. Gastroenterology 2008
or IgA. Two weeks postoperatively a decrease in serum levels of ASCA IgG (p = 0.03) and an increase in ASCA IgA (p = 0.01) could be detected. These returned to pre-operative levels by month 4 and significant changes in serum ASCA titers could not be detected, neither during the 12 months follow-up (n=60) nor during further follow-up (median 101 month, range 90 - 180 months) in 41 patients. Surgical recurrence occurred in 9/41 patients (22%) with follow-up beyond 12 months. Baseline ASCA IgA and IgG antibody response was neither qualitatively nor quantitatively a predictor of risk for re-operation (p>0.05). Conclusions: ASCA serum titers remain reliably stable even after curative intestinal resection. Our data suggest that ASCA as stand alone serologic marker appears not helpful to predict surgical recurrence in an adult cohort of patients with CD. S1098 Patient Preferences for Crohn's Disease: A Discrete Choice Experiment in Flare-Up and Maintenance Therapy Xavier Calvet, Carlos Taxonera, Elena Ricart, Daniel Ginard, Antonio López-San Román, Javier P. Gisbert, Francesc Casellas, Josep Darbá, Gabriela Restovic, Francisco Javier Sabater OBJECTIVE: To identify patient preferences regarding various aspects of Crohn's disease (CD) flare-up and maintenance therapy for CD patients in Spain. METHODS: The main attributes of CD flare-up or maintenance treatment were determined from a review of the literature and consultations with medical experts and patients. The discrete choice experiment included the following attributes: type of drug administration, disease control, mild-tomoderate adverse events, aesthetic adverse events, serious adverse events and tumor incidence, plus a cost attribute in order to estimate willingness to pay (WTP) for improvements in attribute levels. One hundred sixty-eight patients filled the questionnaire for flare-up therapy and 208 patients the one for maintenance therapy for CD. They were presented with pairs of hypothetical treatment profiles with varied levels of adverse events, disease control, type of administration, tumor incidence and cost. Questions were also included to collect socio-demographic data. Data were analyzed using a random effects probit model. RESULTS: All attributes had the expected polarity and all were significant predictors of choice, except for mild-to-moderate adverse events, which was excluded from both analyses. Patients in flare-up therapy were WTP €144.4/month for a 10% reduction in the probability of experiencing serious adverse events. WTP for a similar reduction in aesthetic adverse events was €5.5/month, and €13.5/month for a 1% increase in the probability of obtaining a clinical response. In the maintenance therapy setting, patients were WTP €1112.4/month for a 1% reduction in the probability of presenting a tumor, €22.7/month for a 1% reduction in the rate of serious adverse events; and €21.1/month for a 1% increase in the probability of obtaining a clinical response. Patients were also willing to pay €276/month and €223/ month to have their treatment administered orally rather than with an injection or an infusion respectively. CONCLUSION: Spanish CD patients have well-defined preferences among treatment attributes and are willing to accept trade-offs. Patients in flare-up therapy indicated that they were willing to accept a high risk of aesthetic adverse events in exchange for clinical efficacy, but only a low risk of serious adverse events. Patients in maintenance therapy were willing to accept quite a high risk of serious adverse events, but only a low risk of neoplasia, in exchange for clinical efficacy. We conclude that patients' perspectives should be taken into account when treatment decisions are taken.
S1096 Pre-Operative Infliximab Exposure and the Occurrence of Post-Operative Complications Following Proctocolectomy and Ileal Pouch-Anal Anastomosis (IPAA) for Ulcerative Colitis (UC) Jason M. Swoger, Edward V. Loftus, Darrell S. Pardi, Sunanda V. Kane, William J. Tremaine, William A. Faubion, David H. Bruining, Eric J. Dozois, John H. Pemberton, Bruce G. Wolff, David W. Larson, Robert R. Cima, Prabin Thapa, William S. Harmsen, Alan R. Zinsmeister, William J. Sandborn Background: IPAA is the surgical procedure of choice for patients (pts) with UC. Many pts receive pre-operative therapy (rx) with an anti-tumor necrosis factor (TNF) antibody. Conflicting data exist regarding the effect of pre-operative anti-TNF rx on post-operative complications. Aims: To describe the association between pre-operative anti-TNF rx and post-operative complications in pts undergoing IPAA for UC. Methods: Pts who underwent IPAA for UC at our institution between 2002-07 were identified. A retrospective chart review was performed. Endpoints were occurrence of any complication, early (<30 d) and late (<6 mo), and early septic complications. Logistic regression, Cox proportional hazard regression, and Poisson regression assessed variables associated with these outcomes. Results: A total of 436 pts underwent IPAA during the study period. Median age at surgery was 38.4 years; 59% were male. Twenty-five percent received anti-TNF rx prior to colectomy, including 64 pts (15%) within 12 weeks of surgery (current). Forty-three percent were receiving immunomodulators and 64% were receiving corticosteroids at surgery. Three hundredfourteen pts (72%) experienced 584 overall complications. Univariate logistic regression showed no significant association between current anti-TNF rx and early complications (OR, 0.8; 95% CI, 0.5-1.4), including septic complications (OR, 1.3; 95% CI, 0.7-2.4). Disease activity, current steroid rx, and number of immunosuppressant medications were not significantly associated with early complications. In a multi-variable model, current anti-TNF rx (relative to none) was associated with early septic complications (OR, 2.5; 95% CI, 1.06.1). Fulminant disease activity (relative to low) and increased BMI were also significantly associated with early infectious complications. A 3-stage surgery was associated with a lower odds of an early infectious complication compared to a 2-stage surgery. A Poisson regression model indicated significant associations for fulminant disease activity (relative to low) with an increased number of early and late complications, and 3-stage surgery (relative to 2stage) with fewer early and late complications. Conclusions: Pre-operative exposure to antiTNF rx may be associated with an increased risk of early infectious complications following colectomy, but not overall early or late complications in UC pts following IPAA. Performing a 3-stage surgery in pre-selected high risk pts is associated with fewer early infectious and overall early and late complications than with a 2-stage surgery.
S1099 Systemic AA Amyloidosis in Crohn's Disease (CD): A Serum Amyloid P Component (SAP) Scintigraphy Study Prayman Sattianayagam, Simon D. Gibbs, Ashutosh Wechalekar, Janet A. Gilbertson, Helen J. Lachmann, Hawkins N. Philip, Julian D. Gillmore Introduction : CD is a recognised cause of AA amyloidosis (AAA), which is characterised by deposition of protein in a fibrillary conformation and consequent organ dysfunction. The AA fibril precursor protein is the acute phase reactant serum amyloid A protein (SAA), which is synthesized in the liver. Amyloid regression and improvement in amyloidotic organ function can occur with reduction of inflammation, in particular SAA concentration. Aims and Methods : To report the natural history and outcome of AAA secondary to CD, as assessed by SAP scintigraphy (a method of serially quantifying whole body amyloid load), and serial SAA (normal 3mg/l) and C-reactive protein (CRP) (normal <0.8mg/l) levels. A review of all AAA cases secondary to CD seen at our institution over a 20 year period (19892008) was undertaken. Results :19 cases (12 male) were identified. Median age at diagnosis of AAA was 37 (range 22-67) and median length of follow-up (FU) was 3.6 years (range 0.2-18). A proteinuric renal presentation was universal and amyloid cardiomyopathy did not occur in any patient during FU. Median time from diagnosis of CD to features of renal dysfunction was 16 years (range 0.1-32). Median time from renal dysfunction to end-stage renal failure (ESRF) in 12 cases was 2 years (range 0.1-9 years). At baseline, splenic, adrenal and hepatic amyloid deposits were present on SAP scintigraphy in 19, 10 and 1 case respectively. Proteinuria completely resolved and renal excretory function remained stable in the only patient whose median SAA remained completely normal throughout 9.5 years of FU. Despite normal CRP levels in 2 patients, amyloid did not regress and renal function did not improve; however, serial SAA measurements of 12 and 16 mg/l indicated ongoing inflammation. Renal transplantation (RTx) was undertaken in 5 cases a median of 1 year (range 0.2-7.3) from ESRF. Median graft survival at censor was 14.5 years (range 1.6-23). Graft failure due to amyloid recurrence occurred in 1 case whose median SAA after RTx was 16.5 mg/l. Despite SAP scan evidence of graft amyloid within 8 years of RTx, this graft survived 14.5 years. Median SAA in each of 4 patients whose amyloid did not recur after RTx was <5 mg/l. Conclusions : AAA in CD presents with proteinuria, typically in the nephrotic range. Cases of CD should be screened for AAA with regular urine dipstick testing. Good control of the underlying inflammation (guided by SAA rather than CRP levels) can result in stabilisation or regression of amyloid and improvement in organ function. RTx is recommended in selected cases of CD-associated AAA provided that inflammation is controlled.
S1097 Impact of Intestinal Resection On and Prognostic Value of Anti-Saccharomyces Cerevisiae Serology in Patients with Crohn's Disease During Long-Term Follow-Up Alexander Eser, Pavol Papay, Wolfgang Miehsler, Clemens Dejaco, Alfred Gangl, Harald Vogelsang, Walter Reinisch Background and objectives: Up to 70 % of patients with Crohn's disease (CD) have to undergo intestinal surgery within 15 years after diagnosis. Serologic markers including antibodies towards Saccharomyces cerevisiae were indicated as predictors of a worse natural course of CD. Here we aimed to investigate the impact of intestinal resection on serum levels of ASCA and the prognostic value of the latter for surgical recurrence during long-term follow-up. Methods: 60 patients undergoing surgery due to stricturing and/or penetrating complications were assayed at time of event, and during postoperative follow up. Serum samples were obtained at baseline (immediately prior to surgery), and after intestinal resection at week 2, months 4, 8, and 12, and thereafter at time of clinic consultation. Data on disease phenotype, surgical recurrence and medication were collected. ASCA titers were determined by ASCA IgG and IgA enzyme-linked immunosorbent assay (QUANTA Lite™ INOVA Diagnostics, Inc., San Diego, California, USA). Results: At baseline 48/60 (80%) of patients were rated as positive for ASCA IgG (median level 42.65 IU, range 3.4 - 655 IU), 46/60 (77%) for ASCA IgA (38.75 IU, 4.1 - 3686 IU) and 52/60 (87%) as positive for either IgG
AGA Abstracts
A-188