Selective blockade of interactions between leukocytes and vascular endothelium in the gut is a promising strategy for the treatment of inflammatory bowel diseases.
MLN02 is a humanized antibody to the alpha-4/beta-7 integrins.
Dr Feagan and colleagues from Canada conducted a multicenter, double-blind, placebo-controlled trial of MLN02 in patients with active ulcerative colitis.
|Clinical remission rates at week 6 was 33% for the group receiving 0.5 mg kg-1 of MLN02|
|New England Journal of Medicine|
The research team randomly assigned 181 patients to receive 0.5 mg of MLN02 per kilogram of body weight in Group 1 or 2.0 mg per kilogram in Group 2.
Group 3 patients were also randomized to receive an identical-appearing placebo intravenously on day 1 and day 29.
The researchers reported that eligible patients also received concomitant mesalamine or no other treatment for colitis.
The team evaluated ulcerative colitis clinical scores and sigmoidoscopic assessments 6 weeks after randomization.
The researchers found that clinical remission rates at week 6 was 33% for the group receiving 0.5 mg of MLN02 per kilogram.
The team also noted that the group receiving 2.0 mg per kilogram had 32% clinical remission rates at week 6.
In comparison, clinical remission rates at week 6 were 14% for the placebo group.
The team observed that the proportions of patients improving by at least 3 points on the ulcerative colitis clinical score was 66% in Group 1, 53% in Group 2 and 33% in Group 3.
The researchers found endoscopic evidence of remission in 28% from Group 1 and 12% in Group 2, as compared with 8% of those receiving placebo.
The minority of patients developed an MLN02 antibody titer greater than 1:125.
The team observed incomplete saturation of the alpha-4/beta-7 receptor on circulating lymphocytes in the patients who developed the MLN02 antibody titer.
The researchers identified no benefit of treatment in the patients who developed an antibody titer.
Dr Feagan's team concludes, “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.”