Posted 7/18/2012 4:15 AM (GMT 0)
more about vedolizumab:
Vedolizumab, a novel drug that selectively blocks lymphocyte trafficking to the gut, was safe and highly effective for inducing and maintaining clinical remission in patients with moderate to severe ulcerative colitis in a pivotal phase III trial.
"If the findings hold up with more detailed analysis, it looks like we’ll have the efficacy of a biologic agent without some of the toxicity issues that we’ve seen with anti-TNF [tumor necrosis factor] drugs," said Dr. William J. Sandborn, professor of medicine and chief of gastroenterology at the University of California, San Diego.
Dr. William J. Sandborn
"This potentially could be a first-line drug," for treating moderate to severe ulcerative colitis, said Dr. Sandborn, a coinvestigator in the study.
"Vedolizumab was more effective than placebo for induction and maintenance treatment, including both anti-TNF–exposed and naive patients," Dr. Brian G. Feagan, the study’s lead investigator, said at the annual Digestive Disease Week. In addition, there was little difference between the vedolizumab and placebo groups in terms of adverse events, serious adverse events, and serious infections, said Dr. Feagan, professor of medicine at Western University in London, Ont.
At the end of a year of maintenance treatment, patients kept on the more frequent vedolizumab dosage tested, 300 mg delivered intravenously once every 4 weeks, showed a potent efficacy effect, surpassing the placebo group in corticosteroid-free clinical remissions by 31 percentage points (45% vs. 14%). "Nothing else is that good," Dr. Sandborn said in an interview. "Steroid-free remission with a delta over placebo of 30% is very impressive, especially when you factor in that many of the patients had failed anti-TNF treatment.
"We thought that vedolizumab would be safer than systemic immunosuppression, and I think the data are consistent with that. This will be a first-line treatment," Dr. Feagan said.
Dr. Brian G. Feagan
Equally important, total worldwide experience with vedolizumab, which now includes about 2,500 patients, has not yet resulted in a single case of progressive multifocal leukoencephalopathy (PML), an adverse effect produced by vedolizumab’s cousin drug, natalizumab (Tysarbi), ’approved for U.S. marketing to treat multiple sclerosis and Crohns disease.
Vedolizumab is a humanized monoclonal antibody that specifically binds to the alpha-4 beta-7 integrin protein that helps move leukocytes into the gut. Natalizumab is a less specific integrin antagonist that affects the protein’s actions and immune-cell trafficking to a variety of body sites, including the brain. Natalizumab "essentially blocks immune surveillance in the brain, and that allows for the JC virus [carried by about 50% of people] to cause PML," explained Dr. Sandborn. In contrast, vedolizumab does not cause "a systemic blockade of lymphocytes trafficking; it only affects a small fraction of lymphocytes, and leaves the brain completely unaffected."
Patients most at risk for PML are those who previously received immunosuppressive treatment with a drug such as azathioprine, methotrexate, or an anti-TNF drug. Patients with that history who received natalizumab for 1-2 years have about a 1 in 500-600 risk for PML, and those who got natalizumab for more than 2 years have a 1% risk.