Natalizumab for Crohn's Disease?
Natalizumab for Crohn's Disease?
Is natalizumab, as described in a recent study published in The New England Journal of Medicine, likely to be as effective or more effective than other biologics, such as infliximab, for the treatment of Crohn's disease?
Natalizumab is a humanized monoclonal antibody to alpha-4 integrins. Integrins are cell surface glycoproteins involved in the adhesion, migration, and activation of immune cells. Therefore, this antibody is expected to minimize inflammation by preventing inflammatory cells from migrating into the lamina propria.
In the recently published study in The New England Journal of Medicine, the most effective dose of natalizumab was found to be 2 doses of 3 mg/kg given 4 weeks apart. This dose had a response rate of 71% (vs 38% with placebo) and a remission rate of 44% (vs 28% with placebo); both differences were statistically significant. The adverse-effect profile was very good. Two percent of patients had an infusion reaction and the remainder of reported adverse events (abdominal pain, arthralgia, colitis, flu-like syndrome, headache, and nausea) were not different from placebo. Response rates of natalizumab are very similar to what has been reported for infliximab, where a single infusion of 5 mg/kg had an 82% response rate (vs 17% with placebo) and a 48% remission rate (vs 4% in placebo).
I suspect that when natalizumab is approved for clinical use, it will be used similarly to infliximab -- namely for the treatment of patients with Crohn's disease who fail to respond to oral agents. Because there are different mechanisms of action involved with natalizumab and infliximab, perhaps combination therapy would offer the best therapeutic advantage.
Is natalizumab, as described in a recent study published in The New England Journal of Medicine, likely to be as effective or more effective than other biologics, such as infliximab, for the treatment of Crohn's disease?
Natalizumab is a humanized monoclonal antibody to alpha-4 integrins. Integrins are cell surface glycoproteins involved in the adhesion, migration, and activation of immune cells. Therefore, this antibody is expected to minimize inflammation by preventing inflammatory cells from migrating into the lamina propria.
In the recently published study in The New England Journal of Medicine, the most effective dose of natalizumab was found to be 2 doses of 3 mg/kg given 4 weeks apart. This dose had a response rate of 71% (vs 38% with placebo) and a remission rate of 44% (vs 28% with placebo); both differences were statistically significant. The adverse-effect profile was very good. Two percent of patients had an infusion reaction and the remainder of reported adverse events (abdominal pain, arthralgia, colitis, flu-like syndrome, headache, and nausea) were not different from placebo. Response rates of natalizumab are very similar to what has been reported for infliximab, where a single infusion of 5 mg/kg had an 82% response rate (vs 17% with placebo) and a 48% remission rate (vs 4% in placebo).
I suspect that when natalizumab is approved for clinical use, it will be used similarly to infliximab -- namely for the treatment of patients with Crohn's disease who fail to respond to oral agents. Because there are different mechanisms of action involved with natalizumab and infliximab, perhaps combination therapy would offer the best therapeutic advantage.