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| |  New Alpha-4 Integrin Antagonist Effective and Well Tolerated in Treatment of Crohn’s Disease: Presented at GASTRO 2009 (UEGW/WCOG) By Sara Freeman LONDON -- December 2, 2009 -- The novel monoclonal antibody AJM300 is well tolerated, and shows promising signs of clinical activity in patients with mild to moderate Crohn’s disease, according to data presented at GASTRO 2009. Coinvestigator Takaaki Kawaguchi, Social Insurance Central General Hospital, Tokyo, Japan, presented findings here on November 23 from a randomised, double-blind, study -- the first in patients with Crohn’s disease -- that assessed the safety and clinical efficacy of 3 doses of AJM300 in comparison with placebo. The study was conducted in 16 centres in Japan and involved 71 patients. Patients in this study had active disease, defined as a Crohn’s disease activity index (CDAI) of 150 or greater, with elevated C-reactive protein levels (above the upper limit of normal). All subjects had to have been treated with stable doses of 5-aminosalicylates, corticosteroids (10 mg/day or less), antibiotics, or enteral nutrition (900 kcal/day or less) for 4 weeks. Individuals were excluded from the study if they had decreased white blood cell counts, a CD4+ cell count of 350/mcL or less, and neurological symptoms based on experience with another alpha-4 integrin inhibitor, natalizumab, and its association with progressive multifocal leucoencephalopathy (PML). Treatment was for 8 weeks, with 18 patients being given 40 mg of AJM300, 17 patients given 120 mg, and 19 given 240 mg; 18 subjects received placebo. The majority of patients had mild to moderate disease. Dr. Kawaguchi reported that peripheral lymphocyte counts were significantly higher in AJM300 than in placebo-treated patients, indicating that the drug was successfully preventing these inflammatory cells from infiltrating the colon. The primary efficacy endpoint was the change in baseline to the end-of-treatment CDAI score, but no significant difference was observed between the 3 AJM300 doses and placebo. A significant reduction in the secondary endpoint of change in the International Organization for the Study of Inflammatory Bowel Disease score, however, was observed in the patients given the highest dose of the novel agent versus placebo (-0.8 vs -0.2, P = .0431). Additionally, patients treated with the 240-mg dose of AJM300 exhibited a significant decrease (10 mg/L) in serum CRP levels from baseline versus placebo. A dose-dependent increase in remission rates, however, was not seen comparing AJM300 with placebo, and placebo rates were high. “The final evaluation showed a significantly higher response rate, at 35.7%, in the 240-mg group,” Dr. Kawaguchi said, but placebo response rates were high. To adjust for this, a subgroup analysis was performed, looking only at patients with a baseline CDAI of 200 or greater. After this, “the response rate in the AJM300 240-mg treatment group seems higher than in the placebo group,” Dr. Kawaguchi reported. Adverse events did not appear to be dose-dependent, with nasopharyngitis occurring in 3 placebo-treated patients (16.7%) and in 2 (11.1%), 1 (5.9%), and 3 (16.7%) of the 40-mg, 120-mg, and 240-mg AJM300-treated patients, respectively. No serious infection or neurological symptoms suggesting PML were observed. “AJM300 was well tolerated and possibly effective in patients with active Crohn’s disease,” Dr. Kawaguchi concluded. Funding for this study was provided by Ajinomoto Co., Inc. GASTRO 2009 is jointly organised by the United European Gastroenterology Federation (UEGF), the World Gastroenterology Organisation (WGO), the World Organisation of Digestive Endoscopy (OMED), and the British Society of Gastroenterology (BSG). [Presentation title: A Randomized, Double-Blind, Placebo-Controlled Trial of Oral Alpha-4 Integrin Inhibitor (AJM300) in Patients With Active Crohn’s Disease. Abstract OP054]
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