Ulcerative Colitis: Vandervoort MK

Feagan BG, Greenberg GR, Wild G, Fedorak RN, Paré P, McDonald JW, Dubé R, Cohen A, Steinhart AH, Landau S, Aguzzi RA, Fox IH, Vandervoort MK. · Robarts Research Institute, London, ON N6A 5K8, Canada. · N Engl J Med. · Pubmed #15958805 links to  free full text

Abstract: 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 alpha4beta7 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 compared 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 alpha4beta7 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.

Sands BE, Sandborn WJ, Feagan B, Löfberg R, Hibi T, Wang T, Gustofson LM, Wong CJ, Vandervoort MK, Hanauer S, Anonymous00103. · MGH Crohn's & Colitis Center and Gastrointestinal Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA. · Gastroenterology. · Pubmed #18602921 No free full text.

Abstract: BACKGROUND & AIMS: Activated granulocytes and monocytes/macrophages are implicated in the pathogenesis of ulcerative colitis. Open-label studies and clinical experience in Japan and Europe have suggested that granulocyte/monocyte apheresis is safe and effective in treating ulcerative colitis. METHODS: We evaluated the efficacy of granulocyte/monocyte apheresis in a randomized, double-blind, sham-controlled trial in patients with active moderate-to-severe ulcerative colitis (Mayo score 6-11) in community-based and tertiary care centers. As intervention, we used granulocyte/monocyte apheresis with the Adacolumn Apheresis System (JIMRO, Ltd, Takasaki, Japan) or sham apheresis in a 2:1 ratio for 9 weeks of treatment in a North American pivotal study (N = 168) and in a smaller, companion study of identical design conducted in Europe and Japan (N = 47). RESULTS: In the pivotal study, clinical remission rates (Mayo score 0-2, with scores of 0 on rectal bleeding and 0 or 1 on endoscopic examination) were 17% and 11% for the granulocyte/monocyte apheresis (n = 112)- and sham-treatment groups, respectively (n = 56; P = .361). Clinical response (Mayo score reduction of >/=3 points from baseline) was observed in 44% and 39% of patients, respectively (P = .620). Similar changes were observed for the apheresis- and sham-treatment groups for endoscopic remission and response, and changes in Mayo and quality-of-life scores. The companion study and pooled data from both studies also yielded similar results. CONCLUSIONS: In this study, granulocyte/monocyte apheresis was well tolerated but did not demonstrate efficacy for induction of clinical remission or response in patients with moderate-to-severe ulcerative colitis.