Background &Aims: Despite treatment with corticosteroids, severe to moderately severe attacks of ulcerative colitis have a high colectomy rate. We intended to find a rescue therapy other than cyclosporin A, which ...Background &Aims: Despite treatment with corticosteroids, severe to moderately severe attacks of ulcerative colitis have a high colectomy rate. We intended to find a rescue therapy other than cyclosporin A, which imposes a high risk of side effects and cyclosporine-related mortality. Methods: This was a randomized double-blind trial of infliximab or placebo in severe to moderately severe ulcerative colitis not responding to conventional treatment. Patients were randomized to infliximab/ placebo either on day 4 after the initiation of corticosteroid treatment if they fulfilled the index criteria for fulminant ulcerative colitis on day 3 or on day 6-8 if they fulfilled index criteria on day 5-7 for a severe or moderately severe acute attack of ulcerative colitis. Results were analyzed according to the intention-to-treat principle. The primary end point was colectomy or death 3 months after randomization. Secondary end points were clinical and endoscopic remission at that time in patients who did not undergo operation. Results: Forty-five patients were included (24 infliximab and 21 placebo). No patient died. Seven patients in the infliximab group and 14 in the placebo group had a colectomy (P =. 017; odds ratio, 4.9; 95%confidence interval, 1.4-17) within 3 months after randomization. No serious side effects occurred. Three patients in the placebo group required operation for septic complications. Conclusions: Infliximab 4-5 mg/kg is an effective and safe rescue therapy in patients experiencing an acute severe or moderately severe attack of ulcerative colitis not responding to conventional treatment.展开更多
Background and aims: An increased occurrence of anti- Saccharomyces cerev/s/ae antibodies (ASCA) is reported in unaffected members of families with Crohn’ s disease. Whether ASCA is a familial trait due to genetic fa...Background and aims: An increased occurrence of anti- Saccharomyces cerev/s/ae antibodies (ASCA) is reported in unaffected members of families with Crohn’ s disease. Whether ASCA is a familial trait due to genetic factors or is caused by exposure to environmental factors is unknown. To assess the genetic influence of ASCA we studied its occurrence in a twin population. Patients and methods: ASCA were analysed in 98 twin pairs with inflammatory bowel disease and were related to clinical phenotype and CARD15/NOD2 genotype. Results: ASCA were more common in Crohn’ s disease than in ulcerative colitis (40/70 (57% ) twins v 5/43 (12% ) twins). Associations with ileal Crohn’ s disease, stricturing/ penetrating behaviour, and young age, but not CARD15/NOD2 were confirmed. ASCA were found in 1/20 (5% ) healthy siblings in discordant monozygotic pairs with Crohn’ s disease compared with 7/27 (26% ) in discordant dizygotic pairs. Using the intraclass correlation coefficient (ICC), no agreement in ASCA titres was observed in discordant twin pairs with Crohn’ s disease, in monozygotic (ICC = - 0.02) or dizygotic (ICC = - 0.26) pairs. In contrast, strong agreement was seen within concordant monozygotic twin pairs with Crohn’ s disease (ICC = 0.76). Conclusions: These findings question the concept of ASCA as a marker of genetic susceptibility for Crohn’ s disease. The agreement in ASCA titres within concordant monozygotic twin pairs with Crohn’ s disease, suggests that the level of increase is genetically determined. We propose that ASCA are a marker of a response to an environmental antigen and that a specific gene(s) other than CARD15/NOD2 determines the level of response and perhaps also specific phenotypic characteristics.展开更多
文摘Background &Aims: Despite treatment with corticosteroids, severe to moderately severe attacks of ulcerative colitis have a high colectomy rate. We intended to find a rescue therapy other than cyclosporin A, which imposes a high risk of side effects and cyclosporine-related mortality. Methods: This was a randomized double-blind trial of infliximab or placebo in severe to moderately severe ulcerative colitis not responding to conventional treatment. Patients were randomized to infliximab/ placebo either on day 4 after the initiation of corticosteroid treatment if they fulfilled the index criteria for fulminant ulcerative colitis on day 3 or on day 6-8 if they fulfilled index criteria on day 5-7 for a severe or moderately severe acute attack of ulcerative colitis. Results were analyzed according to the intention-to-treat principle. The primary end point was colectomy or death 3 months after randomization. Secondary end points were clinical and endoscopic remission at that time in patients who did not undergo operation. Results: Forty-five patients were included (24 infliximab and 21 placebo). No patient died. Seven patients in the infliximab group and 14 in the placebo group had a colectomy (P =. 017; odds ratio, 4.9; 95%confidence interval, 1.4-17) within 3 months after randomization. No serious side effects occurred. Three patients in the placebo group required operation for septic complications. Conclusions: Infliximab 4-5 mg/kg is an effective and safe rescue therapy in patients experiencing an acute severe or moderately severe attack of ulcerative colitis not responding to conventional treatment.
文摘Background and aims: An increased occurrence of anti- Saccharomyces cerev/s/ae antibodies (ASCA) is reported in unaffected members of families with Crohn’ s disease. Whether ASCA is a familial trait due to genetic factors or is caused by exposure to environmental factors is unknown. To assess the genetic influence of ASCA we studied its occurrence in a twin population. Patients and methods: ASCA were analysed in 98 twin pairs with inflammatory bowel disease and were related to clinical phenotype and CARD15/NOD2 genotype. Results: ASCA were more common in Crohn’ s disease than in ulcerative colitis (40/70 (57% ) twins v 5/43 (12% ) twins). Associations with ileal Crohn’ s disease, stricturing/ penetrating behaviour, and young age, but not CARD15/NOD2 were confirmed. ASCA were found in 1/20 (5% ) healthy siblings in discordant monozygotic pairs with Crohn’ s disease compared with 7/27 (26% ) in discordant dizygotic pairs. Using the intraclass correlation coefficient (ICC), no agreement in ASCA titres was observed in discordant twin pairs with Crohn’ s disease, in monozygotic (ICC = - 0.02) or dizygotic (ICC = - 0.26) pairs. In contrast, strong agreement was seen within concordant monozygotic twin pairs with Crohn’ s disease (ICC = 0.76). Conclusions: These findings question the concept of ASCA as a marker of genetic susceptibility for Crohn’ s disease. The agreement in ASCA titres within concordant monozygotic twin pairs with Crohn’ s disease, suggests that the level of increase is genetically determined. We propose that ASCA are a marker of a response to an environmental antigen and that a specific gene(s) other than CARD15/NOD2 determines the level of response and perhaps also specific phenotypic characteristics.
