Reframing Disability In Multiple Sclerosis: Addressing Unmet Needs Beyond Relapse

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Ryan Haumschild, PharmD, MS, MBA, CPEL; and Patricia K. Coyle, MD, discuss how progression independent of relapse activity (PIRA) represents a critical driver of disability in multiple sclerosis that requires new therapeutic approaches, biomarkers for early identification, and treatment strategies that address both the relapsing inflammatory component and the underlying smoldering neurodegeneration that manifests clinically around midlife.

Episodes

June 27th 2025EP. 1: Understanding PIRA and Its Clinical Significance in MS

Ryan Haumschild, PharmD, MS, MBA, CPEL;Patricia K. Coyle, MD

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.

June 27th 2025EP. 2: Measuring What Matters: Evidence and End Points That Define Disability in MS

Ryan Haumschild, PharmD, MS, MBA, CPEL;Patricia K. Coyle, MD

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.

July 4th 2025EP. 3: Closing the Gaps: Therapeutic Performance and the Promise of Innovation

Ryan Haumschild, PharmD, MS, MBA, CPEL;Patricia K. Coyle, MD

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.

July 4th 2025EP. 4: Digging Deeper: Mechanisms of Progression and the Case for a Dual Therapeutic Approach

Ryan Haumschild, PharmD, MS, MBA, CPEL;Patricia K. Coyle, MD

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.

July 11th 2025EP. 5: Aligning Evidence With Access: Disability Outcomes, Data, and Payer Decision-Making

Ryan Haumschild, PharmD, MS, MBA, CPEL;Patricia K. Coyle, MD

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.