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Evolving Understanding and Treatment of Smoldering Multiple Sclerosis: Antonio Scalfari, MD, PhD

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The consultant neurologist at Imperial College Healthcare Trust discussed how smoldering MS challenges traditional views of disease progression, seeking combined therapies targeting both inflammatory activity and mechanisms driving smoldering-associated worsening. [WATCH TIME: 4 minutes]

WATCH TIME: 4 minutes

"The progressive disease [has been] there since the beginning, it manifests itself with the smoldering-associated worsening along with relapses. Therefore, the 2 components are coexisting at the same time. Biologically, that makes sense very much."

Prior research has shown that the gradual accumulation of disability in multiple sclerosis (MS) is driven by underlying smoldering processes which remains an under-addressed therapeutic target, according to experts in the field. In a recent paper published in Annals of Neurology, lead author Antonio Scalfari, MD, PhD, and colleagues established the concept of smoldering-associated-worsening (SAW) in MS, addressing both physical and cognitive symptoms.1 The developed consensus-based framework covered identifying smoldering MS and potential biomarkers for tracking SAW. Authors also highlighted the importance of integrating smoldering MS into future clinical practice and research.

According to a story released by Sanofi, the company is currently performing ongoing research to find drivers and pathways of smoldering neuroinflammation in MS. The company noted that identifying such processes can enable new approaches to recognize and address SAW, holding promise to improve care for patients with MS in the future.2 Recently, Sanofi announced that it plans to present results from its phase 3 HERCULES study (NCT04411641) as well as others of tolebrutinib, an investigational Bruton Tyrosine kinase (BTK) inhibitor, in relapsing MS at the upcoming European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) meeting in Copenhagen, Demark, September 20, 2024.3

Following the recent publication of the consensus paper, Scalfari, a consultant neurologist at Imperial College Healthcare Trust and Northwest London Healthcare Trust, sat down with NeurologyLive® to have a conversation about how smoldering MS differs from the traditional understanding of MS progression based on previous research. Scalfari, who also serves as an honorary senior clinical lecturer at Imperial College London, talked about potential markers or biological mechanisms that may be researched to monitor smoldering disease activity in MS. Additionally, he spoke about how innovative therapies, such as the BTK inhibitors, might impact future treatment approaches for the disease.

REFERENCES
1. Scalfari A, Traboulsee A, Oh J, et al. Smouldering-Associated Worsening in Multiple Sclerosis: An International Consensus Statement on Definition, Biology, Clinical Implications, and Future Directions. Ann Neurol. Published online July 25, 2024. doi:10.1002/ana.27034
2. Why Smoldering Neuroinflammation Must Be Part of the Discussion to Improve Care in Multiple Sclerosis. Sanofi. Published September 13, 2024. Accessed September 13, 2024. https://www.sanofi.com/en/magazine/your-health/smoldering-neuroinflammation-discussion-multiple-sclerosis
3. Press Release: Tolebrutinib meets primary endpoint in HERCULES phase 3 study, the first and only to show reduction in disability accumulation in non-relapsing secondary progressive multiple sclerosis. News release. Sanofi. September 2, 2024. Accessed September 3, 2024. https://www.sanofi.com/en/media-room/press-releases/2024/2024-09-02-05-00-00-2938875
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