Can rheumatologists stop causing demyelinating disease?

Area of Science:

• Immunology
• Neurology
• Pharmacology

Background:

• Clinical trials reveal disease pathogenesis through therapy responses.
• CD20 depleters treat autoimmune conditions, suggesting shared immune mechanisms.
• Tumor necrosis factor (TNF) inhibitors for rheumatoid arthritis (RA) rarely induce demyelinating diseases, including multiple sclerosis (MS).

Purpose of the Study:

• To explore the biological basis linking arthritis treatments to demyelinating disease development.
• To provide a B cell-centered perspective on this association.

Main Methods:

• Review of existing literature on TNF inhibitors, tyrosine kinase inhibitors, and Janus kinase inhibitors.
• Analysis of drug mechanisms of action and their effects on immune cells and the central nervous system (CNS).

Main Results:

• Disease-modifying anti-rheumatic drugs causing demyelination often inhibit TNF-receptor signaling and have limited activity on memory B cells.
• These drugs are frequently excluded from the CNS, failing to target ectopic B cell follicles.
• CNS-penetrant agents like ibudilast and some Janus kinase inhibitors do not appear to induce demyelination and may be neuroprotective.

Conclusions:

• Demyelination-inducing RA drugs share features like TNF-receptor inhibition and CNS exclusion.
• Targeting ectopic B cell follicles in the CNS may be crucial for preventing demyelination.
• Development of CNS-penetrant therapies could mitigate these treatment-related CNS complications.