Increased MRI activity and immune activation in two multiple sclerosis patients treated with the monoclonal anti-tumor necrosis factor antibody cA2

TLDR

TNF‑α antibody therapy has shown benefit in animal MS models and human inflammatory diseases, yet no reports exist for MS treatment. We administered intravenous cA2 to two rapidly progressive MS patients in an open‑label phase I safety trial, monitoring clinical status, gadolinium‑enhanced MRI, and peripheral blood and CSF immune markers. The treatment produced no clinical improvement but transiently increased gadolinium‑enhancing lesions and CSF leukocytes/IgG, indicating immune activation and heightened disease activity, so further use of cA2 in MS is not recommended and other TNF‑α antagonists should be closely monitored.

Abstract

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