Tumour Necrosis Factor Neutralization in MS: A Cautionary Tale

Lenercept, a tumour necrosis factor (TNF) capture molecule, was tested in a double- blind, placebocontrolled Phase II trial in multiple sclerosis (MS). Most patients had relapsing-remitting disease. The code was broken once all patients had been treated for at least 24 weeks. Patients on the drug experienced one and a half times as many MS attacks as those on placebo. MS attacks lasted one and a half times as long in those on the drug as those on placebo. Additionally, MS-related complaints voiced by patients on drug were much increased. Prior studies of TNF capture molecules in animals with experimental autoimmune encephalomyelitis turned out to have been counter-predictive. Surprisingly, magnetic resonance imaging scans performed every 4 weeks over the course of the trial, immediately prior to intravenous dosing, were uninformative. The lenercept trial findings raise concerns about other agents that lower TNF levels and that are sometimes given to MS patients. As an example, the possibility is discussed that cyclo propyl-substituted fluoroquinolone antibiotics, of which ciprofloxacin is the most studied, may provoke worsening of MS because of their TNF-inhibiting properties.