New Consensus for Smoldering Disease in MS

CHARACTERISTICS OF SMOLDERING DISEASE IN MS
Smoldering disease in multiple sclerosis is a term used to describe a chronic pathobiological process that occurs in the central nervous system (CNS) beyond acute focal inflammation. It’s characterized by the presence of smoldering lesions, which are a specific type of lesion observed in people living with MS that is chronically active and grows slowly over many years. Smoldering lesions are also known as rim lesions, chronic active lesions, or slowly expanding lesions, and they differ from normal MS lesions in terms of appearance and behavior. Smoldering lesions present with dark, expanding rims around their light centers. They’re common in people living with MS and can affect anyone, regardless of the type of MS someone has or whether someone has a history of taking a disease-modifying therapy. However, they’re generally associated with progressive, more aggressive, and damaging forms of MS.

SMOLDERING DISEASE PROCESS
The smoldering process within the brain is thought to drive disability, regardless of where a patient is on the spectrum of disease–relapsing-remitting MS (RRMS), primary progressive MS (PPMS), progressive-relapsing MS (PRMS), and secondary progressive MS (SPMS). Evidence shows that the smoldering process starts early on and leads to more disability as it continues. Scientists suspect that “smolders” are visual evidence of aggressive microglia activity in the brain, which is activated by inflammatory responses and cleans up cell fragments, waste, and foreign material, such as viruses. For people with MS, however, microglia might also nibble the edges of otherwise inactive lesions, which can enlarge them and lead to disabling damage.

IDENTIFYING SMOLDERS
Using MRIs to identify smolders allows medical professionals to apply more aggressive and targeted therapies to prevent further damage during an active course of MS. A deeper understanding of smoldering disease will optimize clinical management, foster drug discovery through the identification of novel targets, and help people with MS understand reasons for their decline.

RESEARCH
New research on smoldering disease was presented at the 2023 ECTRIMS-ACTRIMS where an international panel developed consensus-driven statements on smoldering disease in multiple sclerosis, including domains. In addition, Sanofi presented new data at the conference evaluating three investigational treatments for MS that target the underlying biology of MS to treat the full spectrum of disease and smoldering neuroinflammation. Furthermore, Tolebrutinib was found to show benefits for up to three years and may help prevent smoldering neuroinflammation in MS. Merck also presented new data on Evobrutinib, an investigational highly selective, oral, central nervous system (CNS)-penetrant BTKi with the potential to transform the RMS treatment landscape by targeting smoldering MS on top of peripheral nervous system inflammation to address both relapses and disability progression independent of relapses. Finally, Bristol Myers Squibb presented new Zeposia (ozanimod) data on long-term disease progression and cognition in patients with relapsing forms of multiple sclerosis.

References
New consensus statements on smoldering disease in multiple sclerosis developed. Practical Neurology. Accessed October 24, 2023. https://practicalneurology.com/news/new-consensus-statements-on-smoldering-disease-in-multiple-sclerosis-developed.

Media update: Sanofi presents new data from robust MS clinical pipeline exploring multiple approaches to address important unmet patient needs. Sanofi. Accessed October 24, 2023. https://www.sanofi.com/en/media-room/press-releases/2023/2023-10-02-06-00-00-2752435.

Lindsey Shapiro P. ECTRIMS 2023: Tolebrutinib show benefits for up to 3 years: ... Multiple Sclerosis News Today. October 17, 2023. Accessed October 24, 2023. https://multiplesclerosisnewstoday.com/news-posts/2023/10/16/ectrims-2023-tolebrutinib-prevents-relapses-lesions-3-years/.

Merck: Unraveling smouldering inflammation in ms. ECTRIMS. September 26, 2023. Accessed October 24, 2023. https://ectrims.eu/msmilan2023-industry-corner/merck-smouldering-inflammation-ms/.

Merck KGaA, Darmstadt, Germany presents new evobrutinib data: Merck KGaA, Darmstadt, Germany. www.merckgroup.com. Accessed October 24, 2023. https://www.merckgroup.com/en/news/ectrims-evobrutinib-11-10-2023.html.

Bristol Myers Squibb Presents new zeposia (ozanimod) data on long-term disease progression and cognition in patients with relapsing forms of multiple sclerosis. News. Accessed October 24, 2023. https://news.bms.com/news/details/2023/Bristol-Myers-Squibb-Presents-New-Zeposia-ozanimod-Data-on-Long-Term-Disease-Progression-and-Cognition-in-Patients-with-Relapsing-Forms-of-Multiple-Sclerosis/default.aspx.

What is smouldering MS? MS One to One EU. Accessed October 24, 2023. https://www.msonetoone.eu/what-smouldering-ms.

Giovannoni G, Popescu V, Wuerfel J, et al. Smouldering multiple sclerosis: The “real MS.” Therapeutic advances in neurological disorders. January 25, 2022. Accessed October 24, 2023. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8793117/.

Bagnato F, Scalfari A, Oh J, et al. International consensus on smoldering disease in multiple sclerosis using the Delphi Method (P11-3.013). Neurology. April 25, 2023. Accessed October 24, 2023. https://n.neurology.org/content/100/17_Supplement_2/3986.

Smoldering multiple sclerosis: Smoldering MS website. Smoldering Neuroinflammation | Multiple Sclerosis Education Site. Accessed October 24, 2023. https://us.smolderingms.com.

Sellman T. Need to know: Smoldering lesions. Multiple Sclerosis News Today. December 11, 2019. Accessed October 24, 2023. https://multiplesclerosisnewstoday.com/news-posts/2019/11/12/need-to-know-about-smoldering-lesions/.