Researchers from England and Wales conducted the trial of natalizumab, a recombinant humanized monoclonal antibody to alpha 4 integrin, in patients with mild to moderately active Crohn's disease.
Alpha 4 integrins are important mediators of leukocyte migration across vascular endothelium.
The pilot study was designed to assess both the safety and efficacy of natalizumab. It was conducted on 30 patients with a Crohn's Disease Activity Index (CDAI) of between 151 and 450.
|With natalizumab, 39% of Crohn's patients achieved remission.
Patients were administered 3 mg/kg of either the alpha 4 antibody (n = 18) or a placebo (n = 12) in the double-blinded, randomized trial.
Success of the treatment was monitored by a change in CDAI at the end of week 2.
CDAI decreased significantly from baseline after infusion of natalizumab (mean, 45 points), but not placebo (mean, 11 points).
In the study, 39% of natalizumab-treated patients achieved remission at week 2. In addition, significant increases of circulating B and T lymphocytes were detected only in this group. However, 11% did require rescue medication at week 2.
In contrast, only 8% of placebo-treated patients had a lower CDAI at week 2 and 33% needed rescue medication.
The frequency of commonly reported adverse events did not differ significantly between groups.
The research group concluded from their findings that a single 3 mg/kg natalizumab infusion was well tolerated by Crohn's disease patients, although the dose used may have been sub-optimal.
They added that elevated circulating lymphocyte levels, after natalizumab administration, suggest interrupted lymphocyte trafficking. Natalizumab therapy in active Crohn's disease merits further investigation.