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  1. Article
  2. Source: Campus Sanofi
  3. Sep 16, 2025

Smoldering Disease Burden

Author: Sanofi

Editorial Team

Smoldering Disease Burden
Smoldering Disease Overview
Mechanism of Smoldering Disease
BTK Enzyme
Smoldering Disease Detection
Disease Progression Monitoring

Despite effective control of relapses and acute lesions, many people with MS continue to accumulate disability.1,2

PIRA is responsible for up to 80% to 90% of disability accumulation in treated RRMS patients4,5*

*As documented by an observational study and pooled data from 2 randomized clinical trials.6,7

Many patients still progress from RRMS to SPMS and accumulate significant disability despite current treatments that effectively address relapses and acute lesions.1,2,15

Approximately
30% to 40%
of treated patients will transition to SPMS within 12 years of RRMS diagnosis6

*As documented by an observational study and pooled data from 2 randomized clinical trials.4,5

PIRA can occur early in the course of MS3,7 

65% of RRMS patients reported experiencing PIRA8,9

PIRA can be seen in treated RRMS patients as early as 3 years after diagnosis3,7

*As seen in real-world data (patient-reported outcomes). PIRA was defined as continuous worsening of symptoms independent of relapses in the previous 12 months.9

The damage from smoldering neuroinflammation can accumulate slowly and manifest as gradual physical and/or cognitive changes over years prior to transitioning to nrSPMS2,12

Physical decline may present as13,14

  • Reduced mobility and having to stop or decrease playing sports, such as tennis, running, etc
  • Debilitating fatigue
  • Worsening bladder and bowel control, vision, speech, and spasticity/dexterity
  • Sexual dysfunction
  • Pain

Cognitive decline may present as13:

  • Trouble concentrating
  • Experiencing difficulty multitasking
  • Being less productive at work, or having more difficulty completing activities at work
  • Brain "fog" and memory impairment
  • Changes in mood/personality and reduced social activities

Symptoms could be gradually building before revealing themselves as clinically detectable disability accumulation, so it is important to continue monitoring patients for
changes over time.2

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

MAT-KW-2500337/v1/Sept2025  

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