Tumour Necrosis Factor Neutralization in MS: A Cautionary Tale.

Area of Science:

• Neuroimmunology
• Pharmacology

Background:

• Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system.
• Tumor Necrosis Factor (TNF) is a pro-inflammatory cytokine implicated in MS pathogenesis.
• TNF capture molecules are investigated as potential MS therapeutics.

Purpose of the Study:

• To evaluate the efficacy and safety of Lenercept, a TNF capture molecule, in patients with relapsing-remitting multiple sclerosis.
• To assess the impact of Lenercept on MS attack frequency, duration, and patient-reported symptoms.

Main Methods:

• A double-blind, placebo-controlled Phase II clinical trial.
• Treatment with Lenercept or placebo for at least 24 weeks in patients with relapsing-remitting MS.
• Monitoring of MS attacks, symptom severity, and magnetic resonance imaging (MRI) scans.

Main Results:

• Patients receiving Lenercept experienced 1.5 times more MS attacks compared to placebo.
• MS attacks were 1.5 times longer in duration for patients on Lenercept.
• Significantly increased MS-related complaints were reported by patients treated with Lenercept.
• MRI scans were uninformative in assessing treatment effects.

Conclusions:

• Lenercept treatment was associated with a worsening of multiple sclerosis disease activity and symptoms.
• Prior animal studies with TNF capture molecules were counter-predictive for MS.
• Findings raise concerns about the use of other TNF-lowering agents, including certain antibiotics like ciprofloxacin, in MS patients.