Observational studyScientific reports2023
The association between disability progression, relapses, and treatment in early relapse onset MS: an observational, multi-centre, longitudinal cohort study.
Observational study in Scientific reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
7 citing papers in PubMed, 9 citations in OpenAlex.
- Plasma-Derived Extracellular Vesicle microRNAs in Multiple Sclerosis: An Exploratory Case-Control Study on Phenotypic Discrimination.International journal of molecular sciences · 2026Article
- Exit strategy patterns in second-line therapies for relapsing forms of multiple sclerosis.Acta neurologica Belgica · 2026Article
- Imbalance of Circulating B-Cell Subsets Was Associated With Higher Risk of Relapses in RRMS Patients.Journal of immunology research · 2026Article
- Characteristics of Disease Relapses and Their Relationships with Weather Conditions in Patients with Multiple Sclerosis.Journal of clinical medicine · 2025Article
- Stable excess mortality in a multiple sclerosis cohort diagnosed 1970-2010.European journal of neurology · 2024Article
- Association of Clinical Relapses With Disease Outcomes in Multiple Sclerosis Patients Older Than 50 Years.Neurology · 2024Article
- Achievement of No Evidence of Disease Activity-3 with Oral Disease-Modifying Treatment in Patients with Relapsing-Remitting Multiple Sclerosis.Saudi journal of medicine & medical sciencesArticle
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The indirect contribution of multiple sclerosis (MS) relapses to disability worsening outcomes, and vice-versa, remains unclear. Disease modifying therapies (DMTs) are potential modulators of this association. Understanding how these endo-phenotypes interact may provide insights into disease pathogenesis and treatment practice in relapse-onset MS (ROMS). Utilising a unique, prospectively collected clinical data from a longitudinal cohort of 279 first demyelinating event cases followed for up to 15 years post-onset, we examined indirect associations between relapses and treatment and the risk of disability worsening, and vice-versa. Indirect association parameters were estimated using joint models for longitudinal and survival data. Early relapses within 2.5 years of MS onset predicted early disability worsening outcomes (HR = 3.45, C.I 2.29-3.61) per relapse, but did not contribute to long-term disability worsening thereinafter (HR = 0.21, C.I 0.15-0.28). Conversely, disability worsening outcomes significantly contributed to relapse risk each year (HR = 2.96, C.I 2.91-3.02), and persisted over time (HR = 3.34, C.I 2.90-3.86), regardless of DMT treatments. The duration of DMTs significantly reduced the hazards of relapses (1st-line DMTs: HR = 0.68, C.I 0.58-0.79; 3rd-line DMTs: HR = 0.37, C.I 0.32-0.44) and disability worsening events (1st-line DMTs: HR = 0.74, C.I 0.69-0.79; 3rd-line DMTs: HR = 0.90, C.I 0.85-0.95), respectively. Results from time-dynamic survival probabilities further revealed individuals having higher risk of future relapses and disability worsening outcomes, respectively. The study provided evidence that in ROMS, relapses accrued within 2.5 years of MS onset are strong indicators of disability worsening outcomes, but late relapses accrued 2.5 years post onset are not overt risk factors for further disability worsening. In contrast, disability worsening outcomes are strong positive predictors of current and subsequent relapse risk. Long-term DMT use and older age strongly influence the individual outcomes and their associations.
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