Human Multiple Sclerosis Patients Exhibit Progression Independent of Relapse Activity
In a study involving 81 MS patients, 21 (25.9%) were identified as exhibiting progression independent of relapse activity (PIRA). A statistical analysis revealed two factors significantly associated with PIRA: fatigue levels measured by the MFIS and CSF levels of CHI3L1. No reliable predictors for relapse-associated worsening were found, and many OCB data were incomplete, leaving certain findings inconclusive.
- Tags
- #MSResearch
- Most relevant to
- —
- Human efficacy
- Not established from this source
- Mechanism
- Not reported
- Evidence strength
- Limited
- Outcome
- Not reported
Why it matters
This study highlights the heterogeneity in disability progression in MS, indicating that fatigue severity and specific biomarkers could help identify patients at risk for PIRA. Understanding these factors is crucial for improving patient outcomes and tailoring management strategies.
What this does not prove
The study lacks specific predictors for relapse-associated worsening and has inconclusive findings related to OCB positivity due to incomplete data. Thus, the findings about PIRA are limited to correlations and do not establish causation.
Next milestone
No next milestone was established from the available source.
Study facts
- Study design
- Observational
- Participants / samples
- 81 · basis not reported
- Randomised
- No
- Controlled
- No
- Primary endpoint met
- Not reported
- Relevant MS type
- Not reported
- Publication date
- 2026-10-13
- Evidence reviewed
- Abstract only
- Regulatory approval
- Not reported
- Research areas
- Not classified
- Biological target
- Not reported
- Pathway
- Not reported
- Population
- Multiple sclerosis patients
- Size of effect
- OR 2.04 for MFIS total score; OR 2.00 for CSF CHI3L1
- Secondary endpoints
- Not reported
- MRI endpoints
- Not reported
- Biomarkers
- Chitinase-3-like protein 1 (CHI3L1)
- Safety
- Not reported
Original sources
- Primary evidenceA 2-year multimodal prospective cohort study to predict sustained progression independent of relapse activity in multiple sclerosis. ↗DOI: 10.3389/fneur.2026.1902455
Supporting passages (18)
subjectsHuman
sample size81
randomizedNo
controlledNo
publication date2026-10-13
primary endpointWe assessed whether a 2-year multimodal evaluation could identify patients who were developing progression independent of relapse activity (PIRA) or relapse-associated worsening (RAW).
findings21 patients (25.9%) met the PIRA criteria
findingsRESULTS: In total, 21 patients (25.9%) met the PIRA criteria, 9 (11.1%) met the RAW criteria, and 1 met both criteria.
findingsA multivariate Firth regression analysis selected two variables associated with PIRA after adjustment: Modified Fatigue Impact Scale (MFIS) total score (OR 2.04, 95% CI 1.17-3.83; p = 0.011) and cerebrospinal fluid (CSF) chitinase-3-like protein 1 (CHI3L1) (OR 2.00, 95% CI 1.11-5.26; p = 0.018).
findingsThe median out-of-sample AUC was 0.74 (95% CI 0.68-0.78).
limitationsNo reliable RAW predictor was found
limitationsOligoclonal immunoglobulin G band (OCB) positivity was universal in PIRA, but the findings are inconclusive due to sparse OCB-negative observations and incomplete OCB data.
populationBACKGROUND: Disability accrual in multiple sclerosis (MS) is heterogeneous.
biomarkersA multivariate Firth regression analysis selected two variables associated with PIRA after adjustment: Modified Fatigue Impact Scale (MFIS) total score (OR 2.04, 95% CI 1.17-3.83; p = 0.011) and cerebrospinal fluid (CSF) chitinase-3-like protein 1 (CHI3L1) (OR 2.00, 95% CI 1.11-5.26; p = 0.018).
effect sizeA multivariate Firth regression analysis selected two variables associated with PIRA after adjustment: Modified Fatigue Impact Scale (MFIS) total score (OR 2.04, 95% CI 1.17-3.83; p = 0.011) and cerebrospinal fluid (CSF) chitinase-3-like protein 1 (CHI3L1) (OR 2.00, 95% CI 1.11-5.26; p = 0.018).
peer reviewedPublication types: Journal Article
subjectsMeSH terms: Humans; Female; Disease Progression; Male; Adult; Prospective Studies; Chitinase-3-Like Protein 1; Middle Aged; Recurrence; Multiple Sclerosis; Disability Evaluation; Fatigue; Follow-Up Studies
study designMeSH terms: Humans; Female; Disease Progression; Male; Adult; Prospective Studies; Chitinase-3-Like Protein 1; Middle Aged; Recurrence; Multiple Sclerosis; Disability Evaluation; Fatigue; Follow-Up Studies
AI assessment, not yet reviewed by a person · version 1 · Community votes are separate from evidence review.