Toward a Standardized Definition of PIRA in Relapsing Multiple Sclerosis

Progression independent of relapse activity (PIRA) is a major contributor to long-term disability in relapsing-remitting multiple sclerosis (RRMS), but inconsistent definitions hinder comparability across studies and adoption by therapeutic regulators. This retrospective cohort study included 33,303 patients with RRMS from the global MSBase registry (2004–2023), testing 360 combinations of PIRA definitions based on variations in baseline setting, disability-progression confirmation period, relapse exclusion windows, and disability-progression thresholds.

PIRA incidence varied widely (0.141–0.658 events per decade), and persistence (no disability improvement over 5 years) ranged from 75% to 92%, depending on the definition. The most-balanced …