BACKGROUND: Infliximab, a chimeric monoclonal antibody directed against tumor necrosis factor α, is an established treatment for Crohn‘s disease but not ulcerative colitis. METHODS: Two randomized, double-blind, pla...BACKGROUND: Infliximab, a chimeric monoclonal antibody directed against tumor necrosis factor α, is an established treatment for Crohn‘s disease but not ulcerative colitis. METHODS: Two randomized, double-blind, placebo-controlled studies -the Active Ulcerative Colitis Trials 1 and 2 (ACT 1 and ACT 2, respectively) -evaluated the efficacy of infliximab for induction and maintenance therapy in adults with ulcerative colitis. In each study, 364 patients with moderate-to-severe active ulcerative colitis despite treatment with concurrent medications received placebo or infliximab (5 mg or 10 mg per kilogram of body weight) intravenously at weeks 0, 2, and 6 and then every eight weeks through week 46 (in ACT 1) or week 22 (in ACT 2). Patients were followed for 54 weeks in ACT 1 and 30 weeks in ACT 2. RESULTS: In ACT 1, 69 percent of patients who received 5 mg of infliximab and 61 percent of those who received 10 mg had a clinical response at week 8, as compared with 37 percent of those who received placebo (P < 0.001 for both comparisons with placebo). A response was defined as a decrease in the Mayo score of at least 3 points and at least 30 percent, with an accompanying decrease in the subscore for rectal bleeding of at least 1 point or an absolute rectal-bleeding subscore of 0 or 1. In ACT 2, 64 percent of patients who received 5 mg of infliximab and 69 percent of those who received 10 mg had a clinical response at week 8, as compared with 29 percent of those who received placebo (P < 0.001 for both comparisons with placebo). In both studies, patients who received infliximab were more likely to have a clinical response at week 30 (P ≤0.002 for all comparisons). In ACT 1, more patients who received 5 mg or 10 mg of inflix imab had a clinical response at week 54 (45 percent and 44 percent, respectively) than did those who received placebo (20 percent, P<0.001 for both comparisons) . CONCLUSIONS: Patients with moderate-to-severe active ulcerative colitis treated with infliximab at weeks 0, 2, and 6 and every eight weeks thereafter were more likely to have a clinical response at weeks 8, 30, and 54 than were those receiving placebo.展开更多
BACKGROUND: Selective blockade of interactions between leukocytes and vascular endothelium in the gut is a promising strategy for the treatment of inflammatory bowel diseases. METHODS: We conducted a multicenter, doub...BACKGROUND: Selective blockade of interactions between leukocytes and vascular endothelium in the gut is a promising strategy for the treatment of inflammatory bowel diseases. METHODS: We conducted a multicenter, double-blind, placebo-controlled trial of MLN02, a humanized antibody to the α 4β 7 integrin, in patients with active ulcerative colitis. We randomly assigned 181 patients to receive 0.5 mg of MLN02 per kilogram of body weight, 2.0 mg per kilogram, or an identical-appearing placebo intravenously on day 1 and day 29. Eligible patients also received concomitant mesalamine or no other treatment for colitis. Ulcerative colitis clinical scores and sigmoidoscopic assessments were evaluated six weeks after randomization. RESULTS: Clinical remission rates at week 6 were 33 percent, 32 percent, and 14 percent for the group receiving 0.5 mg of MLN02 per kilogram, the group receiving 2.0 mg per kilogram, and the placebo group, respectively (P=0.03). The corresponding proportions of patients who improved by at least 3 points on the ulcerative colitis clinical score were 66 percent, 53 percent, and 33 percent (P=0.002). Twenty-eight percent of patients receiving 0.5 mg per kilogram and 12 percent of those receiving 2.0 mg per kilogram had endoscopically evident remission, as com-pared with 8 percent of those receiving placebo (P=0.007). For the minority of patients in whom an MLN02 antibody titer greater than 1∶ 125 developed, incomplete saturation of the α 4β 7 receptor on circulating lymphocytes was observed and no benefit of treatment was identifiable. CONCLUSIONS: In this short-term study, MLN02 was more effective than placebo for the induction of clinical and endoscopic remission in patients with active ulcerative colitis.展开更多
Background: Targeting tumour necrosis factor α(TNF-α) has demonstrated effi cacy in Crohn’s disease. Aim: To evaluate CDP571, a humanised antibody to TNF- α, for treating active Crohn’s disease. Patients: A total...Background: Targeting tumour necrosis factor α(TNF-α) has demonstrated effi cacy in Crohn’s disease. Aim: To evaluate CDP571, a humanised antibody to TNF- α, for treating active Crohn’s disease. Patients: A total of 396 patients with moderate to severe Crohn’s disease. Methods: In a 28 week, randomised, double blind, placebo controlled trial, patients received intravenous CDP571 (10 mg/kg) or placebo every eight weeks to week 24. The primary outcome measure was clinic al response (a decrease in the Crohn’s disease activity index (CDAI) to ≥100 p oints or remission (CDAI score ≤150 points)) at week 28. A secondary outcome me asure was clinical response (using the same definition) at week 2. Results: Clin ical response occurred at week 28 in 80/263 (30.4%) CDP571 patients and 31/132 (23.5%) placebo patients (p = 0.102). Clinical response at week 2 occurred in 9 0/263 (34.2%) CDP571 patients and 28/132 (21.2%) placebo patients (p = 0.011). Post hoc exploratory subgroup analysis of 159 patients with baseline C reactive protein (CRP) ≥10 mg/l demonstrated significant differences between CDP571 and placebo in clinical response rates at weeks 2 (CDP571, 50/101 (49.5%); placebo , 9/58 (15.5%); p<0.001) and 28 (CDP571, 29/101 (28.7%); placebo, 7/58 (12.1% ); p = 0.018). Adverse events occurred at similar frequencies in both treatment groups. Conclusions: CDP571 is modestly effective for short but not long term tr eatment of unselected patients with moderate to severe Crohn’s disease. The cli nical relevance of this short term effect is unclear. Post hoc analysis suggests both short and long term efficacy of CDP571 in patients with elevated baseline CRP (≥10 mg/l). CDP571 is well tolerated.展开更多
文摘BACKGROUND: Infliximab, a chimeric monoclonal antibody directed against tumor necrosis factor α, is an established treatment for Crohn‘s disease but not ulcerative colitis. METHODS: Two randomized, double-blind, placebo-controlled studies -the Active Ulcerative Colitis Trials 1 and 2 (ACT 1 and ACT 2, respectively) -evaluated the efficacy of infliximab for induction and maintenance therapy in adults with ulcerative colitis. In each study, 364 patients with moderate-to-severe active ulcerative colitis despite treatment with concurrent medications received placebo or infliximab (5 mg or 10 mg per kilogram of body weight) intravenously at weeks 0, 2, and 6 and then every eight weeks through week 46 (in ACT 1) or week 22 (in ACT 2). Patients were followed for 54 weeks in ACT 1 and 30 weeks in ACT 2. RESULTS: In ACT 1, 69 percent of patients who received 5 mg of infliximab and 61 percent of those who received 10 mg had a clinical response at week 8, as compared with 37 percent of those who received placebo (P < 0.001 for both comparisons with placebo). A response was defined as a decrease in the Mayo score of at least 3 points and at least 30 percent, with an accompanying decrease in the subscore for rectal bleeding of at least 1 point or an absolute rectal-bleeding subscore of 0 or 1. In ACT 2, 64 percent of patients who received 5 mg of infliximab and 69 percent of those who received 10 mg had a clinical response at week 8, as compared with 29 percent of those who received placebo (P < 0.001 for both comparisons with placebo). In both studies, patients who received infliximab were more likely to have a clinical response at week 30 (P ≤0.002 for all comparisons). In ACT 1, more patients who received 5 mg or 10 mg of inflix imab had a clinical response at week 54 (45 percent and 44 percent, respectively) than did those who received placebo (20 percent, P<0.001 for both comparisons) . CONCLUSIONS: Patients with moderate-to-severe active ulcerative colitis treated with infliximab at weeks 0, 2, and 6 and every eight weeks thereafter were more likely to have a clinical response at weeks 8, 30, and 54 than were those receiving placebo.
文摘BACKGROUND: Selective blockade of interactions between leukocytes and vascular endothelium in the gut is a promising strategy for the treatment of inflammatory bowel diseases. METHODS: We conducted a multicenter, double-blind, placebo-controlled trial of MLN02, a humanized antibody to the α 4β 7 integrin, in patients with active ulcerative colitis. We randomly assigned 181 patients to receive 0.5 mg of MLN02 per kilogram of body weight, 2.0 mg per kilogram, or an identical-appearing placebo intravenously on day 1 and day 29. Eligible patients also received concomitant mesalamine or no other treatment for colitis. Ulcerative colitis clinical scores and sigmoidoscopic assessments were evaluated six weeks after randomization. RESULTS: Clinical remission rates at week 6 were 33 percent, 32 percent, and 14 percent for the group receiving 0.5 mg of MLN02 per kilogram, the group receiving 2.0 mg per kilogram, and the placebo group, respectively (P=0.03). The corresponding proportions of patients who improved by at least 3 points on the ulcerative colitis clinical score were 66 percent, 53 percent, and 33 percent (P=0.002). Twenty-eight percent of patients receiving 0.5 mg per kilogram and 12 percent of those receiving 2.0 mg per kilogram had endoscopically evident remission, as com-pared with 8 percent of those receiving placebo (P=0.007). For the minority of patients in whom an MLN02 antibody titer greater than 1∶ 125 developed, incomplete saturation of the α 4β 7 receptor on circulating lymphocytes was observed and no benefit of treatment was identifiable. CONCLUSIONS: In this short-term study, MLN02 was more effective than placebo for the induction of clinical and endoscopic remission in patients with active ulcerative colitis.
文摘Background: Targeting tumour necrosis factor α(TNF-α) has demonstrated effi cacy in Crohn’s disease. Aim: To evaluate CDP571, a humanised antibody to TNF- α, for treating active Crohn’s disease. Patients: A total of 396 patients with moderate to severe Crohn’s disease. Methods: In a 28 week, randomised, double blind, placebo controlled trial, patients received intravenous CDP571 (10 mg/kg) or placebo every eight weeks to week 24. The primary outcome measure was clinic al response (a decrease in the Crohn’s disease activity index (CDAI) to ≥100 p oints or remission (CDAI score ≤150 points)) at week 28. A secondary outcome me asure was clinical response (using the same definition) at week 2. Results: Clin ical response occurred at week 28 in 80/263 (30.4%) CDP571 patients and 31/132 (23.5%) placebo patients (p = 0.102). Clinical response at week 2 occurred in 9 0/263 (34.2%) CDP571 patients and 28/132 (21.2%) placebo patients (p = 0.011). Post hoc exploratory subgroup analysis of 159 patients with baseline C reactive protein (CRP) ≥10 mg/l demonstrated significant differences between CDP571 and placebo in clinical response rates at weeks 2 (CDP571, 50/101 (49.5%); placebo , 9/58 (15.5%); p<0.001) and 28 (CDP571, 29/101 (28.7%); placebo, 7/58 (12.1% ); p = 0.018). Adverse events occurred at similar frequencies in both treatment groups. Conclusions: CDP571 is modestly effective for short but not long term tr eatment of unselected patients with moderate to severe Crohn’s disease. The cli nical relevance of this short term effect is unclear. Post hoc analysis suggests both short and long term efficacy of CDP571 in patients with elevated baseline CRP (≥10 mg/l). CDP571 is well tolerated.
