Biological Assessment and Mri Monitoring of the Therapeutic Efficacy of a Monoclonal Anti-T Cd4 Antibody in Multiple Sclerosis Patients

Abstract

An initial group of 21 patients plus a second group of 14 patients with active multiple sclerosis (MS) (18 progressive and 17 relapsing-remitting forms) were treated with a murine monoclonal anti-T CD4/BF5 antibody as part of a phase 1 open trial. Tolerance was relatively good: minor general side-effects occurred in 22 patients only upon the first mAb infusion. One year later, functional disability was stabilised in only six of the 35 patients and after 2 years in two patients only (among 21). One year after treatment, nine of the 17 relapsing-remitting patients were relapse-free. CD4 counts decreased dramatically 2 h after treatment These counts were back to baseline counts at 3 months. A transient increase was found in IL-6 and TNFα levels 2 h after treatment, which probably accounts for the observed side effects. Cell adhesion molecule levels were not modified. Serial MRI scans were performed in the second group of 14 patients. In all of these patients, lesion modifications were observed in the three scans performed prior to treatment Yet, no changes in the lesions were noted on the MRI scans performed over the following 3 months. These findings demonstrate the feasibility of this treatment insofar as it induced a marked CD4 lymphocyte depletion. However, it did not seem to stabilise the evolution of the disease – although one must be careful in drawing such conclusions in a phase 1 trial – or to curb the evolution of MRI-documented lesions.