Toward a Unified Definition of Progression Independent of Relapse Activity in Multiple Sclerosis, 2025, Emilio Portaccio et al

[Mij]

Abstract​

Objectives ​

Progression 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.

Methods​

Patients 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.

Results​

A 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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[Mij]

A "roving baseline" is a method used in medical studies, particularly in MS research, where the starting point for measuring disability progression is reset whenever a patients condition improves.

Instead of using a single, fixed baseline score, a roving baseline updates the reference point to the patient's current value after any confirmed improvement. This allows for more sensitive detection of future worsening, as even a small increase from the most recent low point can be flagged as progression, though it may be more prone to overcounting minor fluctuations.