INCREASED MRI ACTIVITY AND IMMUNE ACTIVATION IN 2 MULTIPLE-SCLEROSIS PATIENTS TREATED WITH THE MONOCLONAL ANTITUMOR NECROSIS FACTOR ANTIBODY CA2

There is evidence that treatment with an antibody to tumor necrosis fa ctor alpha (TNF alpha) improves an animal model of multiple sclerosis (MS) and is beneficial in two systemic inflammatory diseases in humans , but there are no reports about anti-TNF treatment of MS. Therefore, we treated two rapidly progressive MS patients with intravenous infusi ons of a humanized mouse monoclonal anti-TNF antibody (cA2) in an open -label phase I safety trial and monitored their clinical status, gadol inium-enhanced brain magnetic resonance imaging (MRI), and peripheral blood and cerebrospinal fluid (CSF) immunologic status. We did not not ice any clinically significant neurologic changes in either patient. T he number of gadolinium-enhancing lesions increased transiently after each treatment in both patients. CSF leukocyte counts and IgG index in creased after each treatment. The transient increase in the number of gadolinium-enhancing lesions that followed each infusion of cA2 togeth er with the increase in cells and immunoglobulin in the CSF of each pa tient suggest that the treatment caused immune activation and an incre ase in disease activity. These results suggest that further use of cA2 in MS is not warranted and that studies of other agents that antagoni ze TNF alpha should be carried out with frequent monitoring of gadolin ium-enhanced MRIs.