Two cases of relapses in primary progressive multiple sclerosis after fingolimod withdrawal

Area of Science:

• Neuroimmunology
• Neurology
• Clinical Medicine

Background:

• Primary progressive multiple sclerosis (PPMS) is a chronic neurological disease characterized by continuous disease progression.
• The INFORMS study evaluated fingolimod's efficacy in PPMS, with results suggesting limited benefit in slowing progression.
• Understanding disease activity in PPMS is crucial for developing effective therapeutic strategies.

Observation:

• Two PPMS patients in the INFORMS cohort experienced a relapse with MRI-identified gadolinium-enhancing lesions three months post-fingolimod withdrawal.
• These cases exhibited clinical and radiological similarities to relapsing-remitting multiple sclerosis (RRMS) patients experiencing similar events.
• The observations suggest that the underlying mechanisms for active demyelination may be present in PPMS.

Findings:

• Active demyelinating plaques, typically associated with relapses in RRMS, appear to be initiated in PPMS.
• Fingolimod withdrawal may trigger or unmask this underlying disease activity in PPMS patients.
• The findings indicate that PPMS pathology might involve processes that can be activated or exacerbated by treatment cessation.

Implications:

• PPMS patients may still benefit from disease-modifying therapies, even if fingolimod shows limited efficacy in slowing overall progression.
• These findings challenge the traditional view of PPMS as solely a non-relapsing, continuously progressive condition.
• Further research is warranted to explore the potential benefits of specific disease-modifying treatments in managing active lesions in PPMS.