In Crohn's disease the migration of leukocytes into the parenchyma and their activation within inflammatory sites are mediated in part by 4 integrins.
In this study, members of the Natalizumab Pan-European Study Group assessed the 4 integrin-specific humanized monoclonal antibody natalizumab.
The team studied 248 patients with moderate to severe Crohn's disease.
They randomly assigned patients to receive 1 of 4 treatments:
- 2 infusions of placebo.
- 1 infusion of 3 mg of natalizumab per kg of body weight, followed by placebo.
- 2 infusions of 3 mg of natalizumab per kg.
- 2 infusions of 6 mg of natalizumab per kg.
Infusions were given 4 weeks apart.
The research team assessed outcomes as changes in Crohn's Disease Activity Index, health-related quality of life, and C-reactive protein levels in the outcomes.
The team found that the group given 2 infusions of 6 mg of natalizumab per kg did not have a significantly higher rate of clinical remission than the placebo group at week 6.
However, both the groups that received 2 infusions of natalizumab had higher remission rates than the placebo group, at multiple time points.
|Natalizumab produced a significant improvement in response rates.|
|New England Journal of Medicine|
In addition, natalizumab produced a significant improvement in response rates.
The highest remission and response rates were found at 6 weeks for the 2 infusion 3 mg group, 44% and 71%, respectively.
The researchers found that the 2 infusions of 6 mg and 3 mg of natalizumab per kg had similar effects.
C-reactive protein levels improved in both groups receiving 2 infusions of natalizumab.
Furthermore, quality of life improved in all natalizumab groups
The team found that rates of adverse events were similar in all 4 groups.
Dr Subrata Ghosh's team concluded, "Treatment with the selective adhesion-molecule inhibitor natalizumab increased the rates of clinical remission and response, improved the quality of life and C-reactive protein levels, and was well tolerated in patients with active Crohn's disease".