title: 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 I 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 TNF alpha 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 I trial--or to curb the evolution of MRI-documented lesions.
authors.affiliation: Service de Neurologie, Hôpital Jean Minjoz, Besançon.
authors.forename: L
authors.initials: L
authors.lastname: Rumbach
authors.forename: E
authors.initials: E
authors.lastname: Racadot
authors.forename: J P
authors.initials: JP
authors.lastname: Armspach
authors.forename: I J
authors.initials: IJ
authors.lastname: Namer
authors.forename: J F
authors.initials: JF
authors.lastname: Bonneville
authors.forename: J
authors.initials: J
authors.lastname: Wijdenes
authors.forename: C
authors.initials: C
authors.lastname: Marescaux
authors.forename: P
authors.initials: P
authors.lastname: Herve
authors.forename: J
authors.initials: J
authors.lastname: Chambron
mesh_terms: D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D000917:Antibody Formation; D015704:CD4 Antigens / Q000276:immunology*; D018450:Disease Progression; D005069:Evaluation Studies as Topic; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016131:Lymphocyte Subsets / Q000276:immunology; D008279:Magnetic Resonance Imaging; D008297:Male; D008991:Monitoring, Physiologic / Q000379:methods*; D009103:Multiple Sclerosis / Q000473:pathology / Q000628:therapy*; D012008:Recurrence
chemical_list: D000911:Antibodies, Monoclonal; D015704:CD4 Antigens