Reframing Disability In Multiple Sclerosis: Addressing Unmet Needs Beyond Relapse

Panelists discuss how progression independent of relapse activity (PIRA) represents a distinct pathological process involving smoldering inflammation and neurodegeneration that drives disability in patients with multiple sclerosis (MS), particularly manifesting around midlife despite being present from disease onset.

Panelists discuss how robust clinical evidence from major studies like the EPIC and OPERA trials demonstrates that progression independent of relapse activity (PIRA) is the primary driver of confirmed disability progression in patients with multiple sclerosis (MS), with clinical parameters over 3 to 6 months being the most meaningful measures of treatment impact.

Panelists discuss how current multiple sclerosis (MS) therapies show limited effectiveness against progression, but emerging Bruton tyrosine kinase (BTK) inhibitors offer promise by targeting both B cells and central nervous system (CNS)–penetrating microglia, with one showing a 31% reduction in confirmed disability progression in clinical trials.

Panelists discuss how chronic neuroinflammation involves distinct mechanisms from acute relapses—including microglial activation, mitochondrial dysfunction, and iron deposition—necessitating dual therapeutic approaches that address relapsing and progressive disease components.

Panelists discuss how emerging biomarkers like neurofilament light protein, glial fibrillary acidic protein (GFAP), cervical cord atrophy, and phase rim lesions could enable earlier identification of patients at risk for progression, supporting more effective treatment decisions and payer coverage determinations based on longitudinal disability data rather than just relapse activity.