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P225 ASSOCIATION BETWEEN GENES POLYMORPHISMS AND INFLIXIMAB DEPENDENT PATIENTS
Abstracts of the 3rd ECCO Congress, Lyon, France, February 28–March 1, 2008 breastfeeding. Patients and Methods: An structured questionnaire with items specifically directed to the study objectives was sent by conventional mailing to 396 IBD female patients of age followed in our center. The questionnaire included a sealed envelop to be returned. Results: 258 (65%) patients answered the questionnaire. Median age 39 years-old (19-85). 178 (69%) women had 316 children, 37% after IBD diagnosis. In those pregnancies that occurred after disease diagnosis, 53% of women were on 5ASA, 22% on thiopurines, and 14% on steroids at the time of conception, and 16% discontinued drug therapy because of medical advice (6% AZA, 10% 5ASA). 18% of pregnants were current smokers, 21% had an IBD flare during pregnancy and 35% in the 6 months following delivery. 12% of patients stated to have had pregnancy-related problems, being the most frequent ones disease relapses, diabetes, and abortion threat. Preterm deliveries were registered in 32% of pregnancies, in a significant higher proportion than in those pregnancies before IBD diagnosis (32% vs 13%, p=0.02). Cesarean section was performed also in a significantly higher number of pregnancies before than after IBD diagnosis (36% vs 8%, p<0.0001). Although there was a trend to a higher incidence of low birth weight in pregnancies before than after IBD diagnosis, this differences did not reach statistical significance (11% vs 5%).Finally, babies that born after the diagnosis of IBD were less often breastfed that those who were born before disease diagnosis (45% vs 66%, p=0.002). Conclusions: In women with IBD, pregnancies occurring after disease diagnosis are associated to a higher rate of cesarean section, low birth weight, and a lower rate of breastfeeding.
P225 ASSOCIATION BETWEEN GENES POLYMORPHISMS AND INFLIXIMAB DEPENDENT PATIENTS D. Duricova Jr. 1 , N. Pedersen 2 , M. Lenicek 3 , M. Elkjaer 2 , P. Munkholm 2 , M. Lukas 4 . 1 General Hospital of 1st Faculty of Medicine, Charles University, Prague, Czech Republic; 2 Herlev University Hospital, Copenhagen, Denmark; 3 Institute of Clinical Biochemistry and Laboratory Diagnostics, Charles University, Prague, Czech Republic; 4 IBD centre, ISCARE IVF a.s., Charles University, Prague, Czech Republic Aim: To assess the association between genotypes and phenotypes, as to the polymorphisms of Casp 9 93 C/T, FasL-843 C/T, LTA 252 C/T, TNF-308 A/G, TNF-857 C/T versus the phenotype of infliximab (IFX) dependent patients. Patients and methods: 190 Crohn' s disease patients from the Danish and Czech Crohn Colitis Database treated with IFX from 1999 to 2006 were included: 76 males, median age 33 yr (15-67), median disease duration 5 yr (0-39), treated in total with 970 IFX infusions, median 3 (1-28). Clinical outcome of IFX therapy was assessed according to Copenhagen phenotype model of IFX dependency (1,2): 1. Immediate response (IR) 30 days after the 1st infusion: Complete response (CR); Partial response (PR); No response (NR) 2. Long-term response (LTR) ≤ 90 days after the last intended IFX: Prolonged (PRO): Maintenance of CR/PR; IFX dependency (ID): Relapse of symptoms after ending IFX requiring repeated IFX to regain CR/PR or repetitive IFX therapy > 1 year to sustain CR/PR; No response (NR) All polymorphisms were typed using PCR-RFLP. Allelic as well as genotype frequencies were calculated and compared by a chi-square test in both patients and controls. P<0.05 was considered statistically significant. Results: 163 (86%) obtained immediate response (102 CR, 61 PR). In LTR 86 (45%) patients became PRO, 58 (31%) ID and 46 (24%) NR. Patients obtaining immediate CR and having at least 1 T allele of FasL-843 C/T polymorphism were more likely to present with the phenotype of infliximab dependency in the long-term than those homozygous for C allele (42% vs 16%, OR 3.9, 95%CI: 1.43-10.61). Similarly, it was revealed that the LTR favorable outcomes (PRO + ID) in patients with immediate PR were associated with the presence of T allele of LTA 252 C/T polymorphism (90% vs 50%, OR 9.2, 95%CI: 1.96-43.15). However, no association was found between the studied polymorphisms and immediate outcome. No difference in allele frequencies between patients and controls was found. Conclusion: Our results suggest that FasL-843 C/T, LTA 252 C/T polymorphisms may have predictive role in long-term response in patients who initially responded to IFX. Presence of T allele of FasL-843 C/T polymorphism was associated with infliximab dependent phenotype. Patients with at least 1 T allele of LTA 252 C/T polymorphism obtained more favorable outcome (PRO+ID). References: 1. Wewer V. JPGN 2006; 42:40-5. 2. Pedersen N. GUT 2006;(abstract) Suppl Nov,vol 55, A 130.
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P226 SURGERY RATE IN PATIENTS WITH CROHN' S DISEASE WITH REGARD TO LONG-TERM CLINICAL OUTCOME OF INFLIXIMAB TREATMENT N. Pedersen 1 , D. Duricova 2 , M. Lenicek 3 , M. Elkjaer 1 , M. Lukas 4 , P. Munkholm 1 . 1 Herlev University Hospital, Copenhagen, Denmark; 2 Department of Gastroenterology, Charles University, Prague, Czech Republic; 3 Institute of Clinical Biochemistry and Laboratory Diagnostics, Charles University, Prague, Czech Republic; 4 IBD centre, ISCARE IVF a.s., Charles University, Prague, Czech Republic Aim: To evaluate the surgery rate in Crohn' s disease (CD) patients with regard to long-term clinical outcome of infliximab (IFX) treatment. Material and methods: 224 Crohn' s disease patients from the Danish and Czech Crohn Colitis Database treated with IFX from 1999 to 2006 were included: 99 males, median age 33 years (15-67), treated in total with 1137 infusions, median 3 (1-28). Indication of IFX was luminal (L) and fistulizing (F) disease in 120 and 104 patients respectively. Median time from diagnosis to the 1st IFX was 6 years (1-39). Median follow up after the 1st infusion was 37 months (12-90). Surgery rate was estimated as number of surgeries/person/year from the diagnosis until the start of IFX therapy and after the 1st infusion until the end of 2006. Surgery was classified as intestinal (resection, stricturoplasty, colectomy) or perianal (fistulotomy, incision of abscess, advancement flap). Long-term clinical outcome ≤ 90 days after the last intended infusion was evaluated in accordance with the Copenhagen phenotype model of IFX dependency (1,2): Prolonged response (PRO): Maintenance of complete or partial response (CR/PR); Infliximab dependency (ID): Relapse of symptoms after ending IFX requiring repeated IFX to regain CR/PR or repetitive IFX therapy >1 year to sustain CR/PR; No response (NR) Wilcoxon signed ranks test was used to compare surgery rates before and after IFX. P<0.05 was considered statistically significant. Results: 108 (48%) patients became PRO, 61 (27%) ID and 55 (25%) NR. 327 surgeries before IFX (58% intestinal, 42% perianal) and 96 (57% intestinal, 43% perianal) after IFX were performed. After IFX therapy, we observed approximately 70% decrease in mean annual surgery rate in PRO (p<0.001) and 57% decrease in ID (p=0.017). A slight nonsignificant increase in NR (9%, p=0.48) was observed. There was a significant reduction of perianal surgeries in PRO (p=0.001) and ID (p=0.011), but not in NR. Intestinal surgery was reduced in PRO (p<0.001). The same trend, however not significant, was observed in ID (p=0.14). Regarding indication, patients with F disease and PRO or ID response had significant decrease of surgery rate after IFX therapy (p<0.001 and p=0.002), however no significant difference was observed in patients with luminal indication. Conclusion: Infliximab treatment seems to be an efficient therapy, significantly decreasing surgery rate in patients responding to IFX treatment (PRO and ID). References: 1. Wewer V. JPGN 2006; 42:40-5. 2. Pedersen N. GUT 2006 (abstract) Suppl Nov, vol 55, A 130.
P227 A POPULATION-BASED CASE-CONTROL STUDY OF POTENTIAL RISK FACTORS FOR IBD P. López, J.L. Perez, T. Perez, C. Fernandez, M. Fernandez. Fundacion Hospital Alcorcon, Madrid, Spain Background: We aimed to purpue potential etiological clues to Crohn' s disease (D) and Ulcerative Colitis (UC) through a population-based case control survey study Methods: Cases with CD (n=124) and UC (n=146), ages 18-80 years were matched by age, gender and geographical location with 239 and 235 subjects respectively. Subjects were administered a multiitem questionnaire about familial history of inflammatory bowel disease, events during the perinatal and infant period, household amenities and family' s socioeconomic status. Results: By univariate analysis some of the variables predictive for CD and UC included living in a city and a best sociocultural status, whereas having pets, bedroom sharing and more frequent infections during childhood were protective for both diseases. For CD to be exposed to gluten before six months of life, tabaquic status and a personal history of allergies were risk factors, whereas breastfeeding was protective. For UC appendectomy and smoking habit were also protective. A seasonal pattern was not observed in the risk to develop IBD. On multivariate analysis variables significantly associated with CD were the best cultural (OR: 1,831; IC 95%:14-2,95) and social (OR:1,68; IC95%:1,22,35) status and living in a urban area (OR: 4,58; IC 95%:2,17-10). Respiratory infections (OR: 0,346; IC 95%:0,23-0,52) and gastroenteritis (OR: 0,55; IC 95%:0,36-0,85) during childhood were protective. For UC in the multivariate analysis, the best cultural (OR: 10,3; IC 95%:2,542) and social (OR: 2; IC95%:1,3- 3,1) status and living in a urban area (OR:
P225 ASSOCIATION BETWEEN GENES POLYMORPHISMS AND INFLIXIMAB DEPENDENT PATIENTS D. Duricova Jr. 1 , N. Pedersen 2 , M. Lenicek 3 , M. Elkjaer 2 , P. Munkholm 2 , M. Lukas 4 . 1 General Hospital of 1st Faculty of Medicine, Charles University, Prague, Czech Republic; 2 Herlev University Hospital, Copenhagen, Denmark; 3 Institute of Clinical Biochemistry and Laboratory Diagnostics, Charles University, Prague, Czech Republic; 4 IBD centre, ISCARE IVF a.s., Charles University, Prague, Czech Republic Aim: To assess the association between genotypes and phenotypes, as to the polymorphisms of Casp 9 93 C/T, FasL-843 C/T, LTA 252 C/T, TNF-308 A/G, TNF-857 C/T versus the phenotype of infliximab (IFX) dependent patients. Patients and methods: 190 Crohn' s disease patients from the Danish and Czech Crohn Colitis Database treated with IFX from 1999 to 2006 were included: 76 males, median age 33 yr (15-67), median disease duration 5 yr (0-39), treated in total with 970 IFX infusions, median 3 (1-28). Clinical outcome of IFX therapy was assessed according to Copenhagen phenotype model of IFX dependency (1,2): 1. Immediate response (IR) 30 days after the 1st infusion: Complete response (CR); Partial response (PR); No response (NR) 2. Long-term response (LTR) ≤ 90 days after the last intended IFX: Prolonged (PRO): Maintenance of CR/PR; IFX dependency (ID): Relapse of symptoms after ending IFX requiring repeated IFX to regain CR/PR or repetitive IFX therapy > 1 year to sustain CR/PR; No response (NR) All polymorphisms were typed using PCR-RFLP. Allelic as well as genotype frequencies were calculated and compared by a chi-square test in both patients and controls. P<0.05 was considered statistically significant. Results: 163 (86%) obtained immediate response (102 CR, 61 PR). In LTR 86 (45%) patients became PRO, 58 (31%) ID and 46 (24%) NR. Patients obtaining immediate CR and having at least 1 T allele of FasL-843 C/T polymorphism were more likely to present with the phenotype of infliximab dependency in the long-term than those homozygous for C allele (42% vs 16%, OR 3.9, 95%CI: 1.43-10.61). Similarly, it was revealed that the LTR favorable outcomes (PRO + ID) in patients with immediate PR were associated with the presence of T allele of LTA 252 C/T polymorphism (90% vs 50%, OR 9.2, 95%CI: 1.96-43.15). However, no association was found between the studied polymorphisms and immediate outcome. No difference in allele frequencies between patients and controls was found. Conclusion: Our results suggest that FasL-843 C/T, LTA 252 C/T polymorphisms may have predictive role in long-term response in patients who initially responded to IFX. Presence of T allele of FasL-843 C/T polymorphism was associated with infliximab dependent phenotype. Patients with at least 1 T allele of LTA 252 C/T polymorphism obtained more favorable outcome (PRO+ID). References: 1. Wewer V. JPGN 2006; 42:40-5. 2. Pedersen N. GUT 2006;(abstract) Suppl Nov,vol 55, A 130.
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P226 SURGERY RATE IN PATIENTS WITH CROHN' S DISEASE WITH REGARD TO LONG-TERM CLINICAL OUTCOME OF INFLIXIMAB TREATMENT N. Pedersen 1 , D. Duricova 2 , M. Lenicek 3 , M. Elkjaer 1 , M. Lukas 4 , P. Munkholm 1 . 1 Herlev University Hospital, Copenhagen, Denmark; 2 Department of Gastroenterology, Charles University, Prague, Czech Republic; 3 Institute of Clinical Biochemistry and Laboratory Diagnostics, Charles University, Prague, Czech Republic; 4 IBD centre, ISCARE IVF a.s., Charles University, Prague, Czech Republic Aim: To evaluate the surgery rate in Crohn' s disease (CD) patients with regard to long-term clinical outcome of infliximab (IFX) treatment. Material and methods: 224 Crohn' s disease patients from the Danish and Czech Crohn Colitis Database treated with IFX from 1999 to 2006 were included: 99 males, median age 33 years (15-67), treated in total with 1137 infusions, median 3 (1-28). Indication of IFX was luminal (L) and fistulizing (F) disease in 120 and 104 patients respectively. Median time from diagnosis to the 1st IFX was 6 years (1-39). Median follow up after the 1st infusion was 37 months (12-90). Surgery rate was estimated as number of surgeries/person/year from the diagnosis until the start of IFX therapy and after the 1st infusion until the end of 2006. Surgery was classified as intestinal (resection, stricturoplasty, colectomy) or perianal (fistulotomy, incision of abscess, advancement flap). Long-term clinical outcome ≤ 90 days after the last intended infusion was evaluated in accordance with the Copenhagen phenotype model of IFX dependency (1,2): Prolonged response (PRO): Maintenance of complete or partial response (CR/PR); Infliximab dependency (ID): Relapse of symptoms after ending IFX requiring repeated IFX to regain CR/PR or repetitive IFX therapy >1 year to sustain CR/PR; No response (NR) Wilcoxon signed ranks test was used to compare surgery rates before and after IFX. P<0.05 was considered statistically significant. Results: 108 (48%) patients became PRO, 61 (27%) ID and 55 (25%) NR. 327 surgeries before IFX (58% intestinal, 42% perianal) and 96 (57% intestinal, 43% perianal) after IFX were performed. After IFX therapy, we observed approximately 70% decrease in mean annual surgery rate in PRO (p<0.001) and 57% decrease in ID (p=0.017). A slight nonsignificant increase in NR (9%, p=0.48) was observed. There was a significant reduction of perianal surgeries in PRO (p=0.001) and ID (p=0.011), but not in NR. Intestinal surgery was reduced in PRO (p<0.001). The same trend, however not significant, was observed in ID (p=0.14). Regarding indication, patients with F disease and PRO or ID response had significant decrease of surgery rate after IFX therapy (p<0.001 and p=0.002), however no significant difference was observed in patients with luminal indication. Conclusion: Infliximab treatment seems to be an efficient therapy, significantly decreasing surgery rate in patients responding to IFX treatment (PRO and ID). References: 1. Wewer V. JPGN 2006; 42:40-5. 2. Pedersen N. GUT 2006 (abstract) Suppl Nov, vol 55, A 130.
P227 A POPULATION-BASED CASE-CONTROL STUDY OF POTENTIAL RISK FACTORS FOR IBD P. López, J.L. Perez, T. Perez, C. Fernandez, M. Fernandez. Fundacion Hospital Alcorcon, Madrid, Spain Background: We aimed to purpue potential etiological clues to Crohn' s disease (D) and Ulcerative Colitis (UC) through a population-based case control survey study Methods: Cases with CD (n=124) and UC (n=146), ages 18-80 years were matched by age, gender and geographical location with 239 and 235 subjects respectively. Subjects were administered a multiitem questionnaire about familial history of inflammatory bowel disease, events during the perinatal and infant period, household amenities and family' s socioeconomic status. Results: By univariate analysis some of the variables predictive for CD and UC included living in a city and a best sociocultural status, whereas having pets, bedroom sharing and more frequent infections during childhood were protective for both diseases. For CD to be exposed to gluten before six months of life, tabaquic status and a personal history of allergies were risk factors, whereas breastfeeding was protective. For UC appendectomy and smoking habit were also protective. A seasonal pattern was not observed in the risk to develop IBD. On multivariate analysis variables significantly associated with CD were the best cultural (OR: 1,831; IC 95%:14-2,95) and social (OR:1,68; IC95%:1,22,35) status and living in a urban area (OR: 4,58; IC 95%:2,17-10). Respiratory infections (OR: 0,346; IC 95%:0,23-0,52) and gastroenteritis (OR: 0,55; IC 95%:0,36-0,85) during childhood were protective. For UC in the multivariate analysis, the best cultural (OR: 10,3; IC 95%:2,542) and social (OR: 2; IC95%:1,3- 3,1) status and living in a urban area (OR: