Summary
This real-world Italian registry study of 16,130 relapsing MS patients with ≥5 years follow-up found that progression independent of relapse activity (PIRA) accounted for 72.3% of confirmed disability accrual events and was the primary driver of long-term disability. Sustained PIRA was strongly associated with transition to secondary progressive MS (73.2% of sustained PIRA cases) compared to non-sustained PIRA (24.8%), suggesting sustained PIRA may represent a more clinically meaningful phenotype marking the onset of progressive disease.
Regional applicability
This study was conducted in Italy using the Italian MS Registry and may have limited direct applicability to UK MS populations, though the pathophysiological insights regarding PIRA-driven disability progression are relevant to understanding MS natural history across health systems. UK clinicians and researchers could consider whether the proposed sustained PIRA definition merits validation in UK registry cohorts.
Key measures
Confirmed disability accrual (6-month confirmed increase in EDSS), sustained disability accumulation, transition to secondary progressive MS, predictors of PIRA and RAW identified via multivariable logistic and ordinal regression
Outcomes reported
The study measured the occurrence and relative contribution of relapse-associated worsening (RAW) and progression independent of relapse activity (PIRA) to confirmed disability accrual and transition to secondary progressive MS over a median follow-up of 11.8 years in 16,130 relapsing-onset patients.
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