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

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.

Etanercept treatment of psoriatic arthritis: Safety, efficacy, and effect on disease progression

“…As reported, 1 patient in the etanercept group developed MS at the end of the blinded phase of the study. While no clinical trials have been done to evaluate etanercept therapy in patients with MS, an increase in disease activity in patients with MS who were treated with other TNF antagonists has been reported (37,38). Overall, however, the risk-benefit profile of etanercept has been highly positive in long-term clinical studies and in postmarketing experience (39).…”

Negative Regulation of Lung Inflammation and Immunopathology by TNF-α during Acute Influenza Infection

“…[3][4][5][6][7][8][9][10][11] TNF-␣, a classical proinflammatory cytokine, has recently been shown to play anti-inflammatory and antifibrotic roles in various models. [32][33][34][35][36][37][38][39][40][41][42][43] However, whether TNF-␣ plays an immunoregulatory role during influenza infection remains unclear. Using a mouse model of respiratory influenza infection, we investigated this issue.…”

TNFα blockade in human diseases: An overview of efficacy and safety

“…A phase II randomized double-blind placebo-controlled trial of 168 MS patients treated with Lenercept, a TNFα receptor IgG1 fusion protein, resulted in an increase in MS exacerbations and a shortened time to flare [69]. In an open-label, phase I safety study, INF was given to two patients with rapidly progressive MS [70]. Both patients had transient increases in the number of lesions on MRI and increases in CSF leukocyte counts and IgG levels, suggesting increased disease activity.…”