摘要
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.
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.
