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.

Panelists discuss how BTK inhibitors represent a promising new oral therapy class that could address both inflammatory and neurodegenerative aspects of MS, particularly for progressive forms where treatment options are limited.

Panelists discuss how payers can evaluate BTK inhibitors by considering specific MS phenotypes and FDA indications rather than applying traditional step therapy protocols that may delay optimal treatment.

Panelists discuss how disability progression can be measured through practical clinical tools like patient-reported outcomes, timed walking tests, and dexterity assessments rather than relying solely on relapse rates.

Panelists discuss how the evaluation process must evolve to accommodate therapies that show benefits in slowing atrophy and motor decline over 1 to 2 years, emphasizing the need for early coverage rather than waiting for extensive long-term data.

Panelists discuss how clinical trials and real-world studies should focus on patients with PIRA who haven’t experienced relapses for extended periods but continue to accumulate disability.

Panelists discuss how patient-reported outcomes are crucial for capturing MS symptoms like fatigue, depression, and cognitive decline that significantly impact working-age patients but require standardization for practical clinical integration.