Shifting Focus to Long-Term Disability and Novel Therapeutic Pathways in Multiple Sclerosis

In Shifting Focus to Long-Term Disability and Novel Therapeutic Pathways in Multiple Sclerosis, Aimee Banks, PharmD, BCPS, MSCS and Millad Sobhanian, PharmD, BCPS delve into focusing on why long-term disability has become a primary treatment focus despite effective relapse-reducing therapies and exploring how BTK inhibitors offer a distinct mechanism of action targeting disease pathways not addressed by current FDA-approved MS treatments.

Although current multiple sclerosis (MS) therapies are highly effective at reducing relapse frequency, long-term disability remains a significant unmet need, driving the field to shift focus beyond short-term inflammatory control. Many patients continue to experience gradual neurologic worsening and functional decline even in the absence of relapses, highlighting the role of neurodegeneration and smoldering disease activity that are not fully addressed by traditional anti-inflammatory treatments. As a result, preventing long-term disability has become a primary treatment priority, emphasizing the need for therapies that target underlying disease mechanisms beyond acute inflammatory events.

Bruton's tyrosine kinase inhibitors (BTKis) represent an emerging class of therapies with a mechanism of action distinct from currently-approved FDA treatments. Unlike conventional disease-modifying therapies, which primarily target circulating immune cells and relapse-driven inflammation, BTKis modulate B-cell and myeloid cell activity within the central nervous system, addressing both peripheral immune activity and compartmentalized neuroinflammation. Investigating this pathway was necessary because existing therapies do not fully prevent the chronic immune-mediated processes that drive progressive disability. By targeting these pathways, BTKis hold the potential to slow or halt long-term disease progression, complementing relapse-focused therapies and offering a new strategy for preserving neurologic function and quality of life for individuals living with MS.

Led by the moderator, the neurology pharmacists examine the following critical questions:

Given how effective current therapies are at reducing relapse rates, what has driven the field to focus more attention on long-term disability as a primary treatment priority?

How does the mechanism of action of BTKi’s differ from other currently-approved FDA-therapies?

Why was it necessary to investigate this disease pathway?

Throughout the conversation, the experts provide a comprehensive reflection on the field and the factors that may shape how clinicians approach care moving forward.

Our next episode, Advancing BTK Inhibitors in MS: Insights from Clinical Trials and Early Safety Data, further explores multiple sclerosis, highlighting key learnings from evobrutinib trials and their implications for the development of other BTK inhibitors, as well as safety and efficacy findings from the HERCULES trial and how they inform clinical use and ongoing investigation of BTK inhibitors in MS.