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Smoldering disease is a key unaddressed component of MS, driving disease progressions1-3

The Silent Progression in MS: Smoldering neuroinflammation and PIRA

Acute Neuroinflammation

 

Acute neuroinflammation is driven in party by activated B cells and T cells derived from the periphery
    • Leads to relapses,acute lesions, and RAW1,8,11

 

10%-20% of disability accumulation in treated patients is driven by relapses and acute lesions 12,13

Smoldering Neuroinflammation

 

Smoldering neuroinflammation is driven in primarily by disease-associated microglia found in the CNS1,8,11
    • Leads to PIRA,resulting in physical disability and cognitive worsening1,8,11

 

80%-90% of disability accumulation in treated patients is relapse-independent and driven by smoldering neuroinflammation.12,13

Both concurrent neuroinflammatory processes drive disability accumulation in MS 1,14-16

Smoldering neuroinflammation starts at disease onset and increasingly drives disability accumulation1

The relative contribution of both acute and smoldering neuroinflammation shifts as patients progress from RRMS to nrSPMS1,14

  • Smoldering neuroinflammation presents early and throughout:the spectrum of MS, before initial clinical symptoms.1,11
  • Over the course of MS, acute neuroinflammation may decline, but smoldering neuroinflammation persists in the absence of relapses and acute lesions1
  • Disability accumulation driven by smoldering neuroinflammation can:
    • Happen throughout the disease spectrum9
    • Affect any patient, regardless of the type of MS or if patients have a history of taking DMTs1
  • Smoldering neuronflammation is driven primarily by disease-associated microglia found in the CNS and contributes to both physical and cognitive disability accumulation1,17

For more information about Acute and Smoldering Inflammation, click on this link:

Acute & Smoldering Neuroinflammation

BBB, blood-brain barrier; BVL, brain volume loss; CNS, central nervous system; LB, B lymphocyte; LT, T lymphocyte; MG, microglia; MP; macrophage; MS, multiple sclerosis.

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  3. Bierhansl L et al. Nat Rev Drug Discov 2022; 21(8): 578–600.
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  12. Kappos L, Wolinsky JS, Giovannoni G, et al. Contribution of relapse independent progression vs relapse-associated worsening to overall confirmed disability accumulation in typical relapsing multiple sclerosis in a pooled analysis of 2 randomized clinical trials. JAMA Neurol. 2020;77(9):1132-1140.
  13. Ingwersen J, Masanneck L, Pawlitzki M, et al. Real-world evidence of ocrelizumab-treated relapsing multiple sclerosis cohort shows changes in progression independent of relapse activity mirroring phase 3 trials. Sci Rep. 2023;13(1):15003. doi:10.1038/s41598-023-40940-w
  14. Filippi M, Amato MP, Centonze D, et al. Early use of high-efficacy disease-modifying therapies makes the difference in people with multiple sclerosis: an expert opinion. J Neurol. 2022;269(10):5382-5394.
  15. Cree BAC, Hollenbach JA, Bove R, et al; University of California, San Francisco MS-Epic Team. Silent progression in disease activity-free relapsing multiple sclerosis. Ann Neurol. 2019;85(5):653-666.
  16. Kreiger SC, Antoine A et al. EDSS 0 is not normal: multiple sclerosis disease burden below the clinical threshold. Mult Scler. 2022;28(14):2299-2303
  17. Correale J, Halfon MJ, Jack D, Rubstein A, Villa A. Acting centrally or peripherally: a renewed interest in the central nervous system penetration of disease-modifying drugs in multiple sclerosis. Mult Scler Relat Disord. 2021;56:103264.doi 10.1016/j.msard.2021.103264
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