Background & Aims: To investigate the efficacy and safety of certolizumab pegol (a polyethylene-glycolated Fab’ frag-ment of anti-tumor necrosis factor, CDP870) in Crohn’ s disease. Methods: In a placebo-control...Background & Aims: To investigate the efficacy and safety of certolizumab pegol (a polyethylene-glycolated Fab’ frag-ment of anti-tumor necrosis factor, CDP870) in Crohn’ s disease. Methods: In a placebo-controlled, phase II study, 292 patients with moderate to severe Crohn’ s disease received subcutaneous certolizumab 100, 200, or 400 mg or placebo at weeks 0, 4, and 8. The primary end point was the percentage of patients with a clinical response at week 12 (a Crohn’ s Disease Activity Index decrease of < 100 points or remission [Crohn’ s Disease Activity Index ≤ 150 points]) in the intent-to-treat population. Results: All certolizumab doses produced significant clinical benefit over placebo at week 2 (placebo, 15.1% ; certolizumab 100 mg, 29.7% [P = .033]; 200 mg, 30.6% [P = .026]; 400 mg, 33.3% [P = .010]). At all time points, the clinical response rates were highest for certolizumab 400 mg, greatest at week 10 (certolizumab 400 mg, 52.8% ; placebo, 30.1% ; P = .006) but not significant at week 12 (certolizumab 400 mg, 44.4% ; placebo, 35.6% ; P = .278). Patients with baseline Creactive protein levels of 10 mg/L or greater (n = 119) showed clearer separation between active treatment and placebo (week 12 clinical res-ponse: certolizumab 400 mg, 53.1% ; placebo, 17.9% ; P = .005; post hoc analysis) owing to a lower placebo response rate than patients with C-reactive protein levels of less than 10 mg/L. Adverse events were similar among groups. Conclusions: Certolizumab 400mg may be effective and iswell tolerated in patients with active Crohn’ s disease. High placebo response rates in the large patient subgroup with low C-reactive protein levels may have obscured statistical separation between certolizumab and placebo. Ongoing phase III trials are necessary to establish the clinical efficacy of certolizumab.展开更多
Objective. There is strong evidence that genetic factors contribute to the susceptibility for inflammatory bowel diseases (IBD). Recently, IL-18 promoter polymorphisms were characterized as risk factors for inflammato...Objective. There is strong evidence that genetic factors contribute to the susceptibility for inflammatory bowel diseases (IBD). Recently, IL-18 promoter polymorphisms were characterized as risk factors for inflammatory diseases such as sepsis, asthma and adult-onset Still’s disease. The aim of this study was to determine whether the -137 (G/C) IL-18 promoter polymorphism was associated with IBD susceptibility. Material and methods. For association analysis, 470 patients with Crohn’s disease (CD), 235 unrelated patients with ulcerative colitis (UC) and 347 controls were enrolled. Furthermore, 233 UC and 470 CD trios were included for segregation analysis. Genotyping was performed by application of the TaqMan MGB biallelic discrimination system. Results. When comparing genotype frequencies of CD and UC patients versus controls, no significant difference was found (p = 0.089 and p =0.078, respectively). However, the Cochran-Armitage trend test revealed a rising probability for CD and UC with increasing number of G alleles (p = 0.030 and 0.028, respectively) for the case-control analysis. On the contrary, the family-based transmission disequilibrium test (TDT) did not show an association of the G allele with CD or UC in 470 CD and 233 UC trios (p = 0.53 and p = 0.79, respectively). Conclusion. The -137 (G/C) IL-18 promoter polymorphism is not a susceptibility factor for IBD in a German cohort.展开更多
文摘Background & Aims: To investigate the efficacy and safety of certolizumab pegol (a polyethylene-glycolated Fab’ frag-ment of anti-tumor necrosis factor, CDP870) in Crohn’ s disease. Methods: In a placebo-controlled, phase II study, 292 patients with moderate to severe Crohn’ s disease received subcutaneous certolizumab 100, 200, or 400 mg or placebo at weeks 0, 4, and 8. The primary end point was the percentage of patients with a clinical response at week 12 (a Crohn’ s Disease Activity Index decrease of < 100 points or remission [Crohn’ s Disease Activity Index ≤ 150 points]) in the intent-to-treat population. Results: All certolizumab doses produced significant clinical benefit over placebo at week 2 (placebo, 15.1% ; certolizumab 100 mg, 29.7% [P = .033]; 200 mg, 30.6% [P = .026]; 400 mg, 33.3% [P = .010]). At all time points, the clinical response rates were highest for certolizumab 400 mg, greatest at week 10 (certolizumab 400 mg, 52.8% ; placebo, 30.1% ; P = .006) but not significant at week 12 (certolizumab 400 mg, 44.4% ; placebo, 35.6% ; P = .278). Patients with baseline Creactive protein levels of 10 mg/L or greater (n = 119) showed clearer separation between active treatment and placebo (week 12 clinical res-ponse: certolizumab 400 mg, 53.1% ; placebo, 17.9% ; P = .005; post hoc analysis) owing to a lower placebo response rate than patients with C-reactive protein levels of less than 10 mg/L. Adverse events were similar among groups. Conclusions: Certolizumab 400mg may be effective and iswell tolerated in patients with active Crohn’ s disease. High placebo response rates in the large patient subgroup with low C-reactive protein levels may have obscured statistical separation between certolizumab and placebo. Ongoing phase III trials are necessary to establish the clinical efficacy of certolizumab.
文摘Objective. There is strong evidence that genetic factors contribute to the susceptibility for inflammatory bowel diseases (IBD). Recently, IL-18 promoter polymorphisms were characterized as risk factors for inflammatory diseases such as sepsis, asthma and adult-onset Still’s disease. The aim of this study was to determine whether the -137 (G/C) IL-18 promoter polymorphism was associated with IBD susceptibility. Material and methods. For association analysis, 470 patients with Crohn’s disease (CD), 235 unrelated patients with ulcerative colitis (UC) and 347 controls were enrolled. Furthermore, 233 UC and 470 CD trios were included for segregation analysis. Genotyping was performed by application of the TaqMan MGB biallelic discrimination system. Results. When comparing genotype frequencies of CD and UC patients versus controls, no significant difference was found (p = 0.089 and p =0.078, respectively). However, the Cochran-Armitage trend test revealed a rising probability for CD and UC with increasing number of G alleles (p = 0.030 and 0.028, respectively) for the case-control analysis. On the contrary, the family-based transmission disequilibrium test (TDT) did not show an association of the G allele with CD or UC in 470 CD and 233 UC trios (p = 0.53 and p = 0.79, respectively). Conclusion. The -137 (G/C) IL-18 promoter polymorphism is not a susceptibility factor for IBD in a German cohort.
