Improving MS Management Through Early Intervention and Precision Medicine: Emilio Portaccio, MD

WATCH TIME: 4 minutes

"Neurologists are increasingly recognizing cognition as a critical feature of the disease, one that is often detectable in its earliest phases."

Progression independent of relapse activity (PIRA) has become a key factor in driving disability accumulation in relapsing multiple sclerosis (MS), yet defining it reliably remains a challenge. A recent cohort study utilizing data from the Italian Multiple Sclerosis Register aimed to address this issue by evaluating the sensitivity, specificity, and predictive accuracy of different PIRA definitions in relation to a hard disability outcome—reaching an Expanded Disability Status Scale (EDSS) score of 6. The study reported that PIRA definitions using a roving baseline combined with a 24-week confirmation of disability progression, excluding relapses in 90 days before or 30 days after confirmed disability accrual (CDA), achieved the best predictive performance, providing a practical framework for clinical and research use.

The study analyzed data from 32,905 patients with MS over an average follow-up of 11.3 years, comparing PIRA definitions based on fixed versus roving baselines, sustained versus 24-week CDA confirmations, and varying relapse exclusion windows. Results showed that using a roving baseline increased CDA detection by 14–16% compared with a fixed baseline. Definitions with a 24-week confirmation period demonstrated strong predictive accuracy, with 69% sensitivity and 68% negative predictive value, making them practical for clinical settings. Conversely, definitions excluding relapses from baseline to CDA confirmation had lower sensitivity. These findings highlight the importance of adapting PIRA definitions to specific clinical or research needs, improving the precision of disability progression evaluation in MS.

At the 2024 European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) Congress, September 18-20, in Copenhagen, Denmark, Emilio Portaccio, MD, professor of neurology at the University of Florence, presented these potential groundbreaking findings on PIRA definitions and their clinical implications. In an interview with NeurologyLive^® at the Congress, Portaccio emphasized the importance of refining early intervention strategies to address the biological onset of MS. He also discussed the limitations of the EDSS as the sole measure of progression, advocating for the inclusion of patient-reported outcomes and advanced imaging techniques to provide a more comprehensive assessment. Additionally, Portaccio highlighted ongoing efforts to standardize the identification of meaningful changes in neuropsychological tests.

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REFERENCES
1. Portaccio E, Betti M, de meo e, et al. Towards an unified definition of progression independent of relapse activity in relapsing multiple sclerosis Towards an unified definition of progression independent of relapse activity in relapsing multiple sclerosis. Presented at: 2024 ECTRIMS; September 18-20; Copenhagen, Denmark. Abstract 2078.