ArticleNeurology2025
Toward a Unified Definition of Progression Independent of Relapse Activity in Multiple Sclerosis.
Article in Neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 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
4 citing papers in PubMed.
- Incidence of Progression Independent of Relapse Activity (PIRA) under platform disease-modifying treatment in multiple sclerosis.Journal of neurology · 2026Article
- Relapse-associated worsening in apolipoprotein E ε4 carriers with relapsing multiple sclerosis.Journal of neurology, neurosurgery, and psychiatry · 2026Article
- Big data in multiple sclerosis.Current opinion in neurology · 2026Review
- From Phenotypes to Spectrum: Rethinking RRMS, SPMS and PPMS in the Era of PIRA-A Framework Integrating PIRA, Smouldering-Associated Worsening, and Neurologic Reserve to Facilitate Earlier Recognition of Progression.Neurology international · 2026Review
Corrections and comments
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Authors and funding
30 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesProgression independent of relapse activity (PIRA) is the main driver of disability accumulation in relapsing multiple sclerosis (MS). We tested various PIRA definitions against the risk of long-term disability.
methodsPatients with relapsing MS, first visit ≥January 1, 2000, ≥3 visits with Expanded Disability Status Scale (EDSS), and ≥5-year follow-up were extracted from the Italian MS and Related Disorders Register on September 29, 2023. Eighteen PIRA definitions were obtained combining fixed or roving baseline, 24-week, 48-week confirmed or sustained disability accrual, no relapses ≤90 days before/≤30 days after the event (90d), ≤180 days before/≤30 days after the event, or absence of relapses from baseline to confirmation score (ABS). Predictive performance against the reaching of EDSS = 6.0 was calculated.
resultsA total of 30,203 patients were included. After a follow-up of 11.3 ± 4.3 years, PIRA ranged from 38.8% to 74.1%. EDSS = 6.0 was detected in 4,401 (15%) patients. Sensitivity of PIRA definitions against EDSS = 6.0 was higher using the 90d criterion (66.7%-69.4%), while the ABS criterion increased specificity (55.3%-62.2%). DISCUSSION: The definition of PIRA combining roving baseline, no relapses 90 days before and 30 days after the event and 24-week confirmation achieved the best predictive value and feasibility, supporting its use in routine practice and research.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.