Author: Marco Meglio – May 29, 2025
Key Takeaways
- Variability in PIRA incidence and persistence is influenced by definition parameters, highlighting the need for a standardized definition in MS research.
- The study analyzed 33,303 patients, revealing that baseline disability and confirmation period significantly affect PIRA detection.
A recent large cohort analysis of global MS registry data reported that the incidence and persistence of progression independent of relapse activity varied widely depending on how it was defined.
Jannis Müller, MD, MSc
Newly published in JAMA Neurology, a retrospective cohort study using MSBase registry data that compared 360 definitions of progression independent of relapse activity (PIRA) in patients with relapsing-remitting multiple sclerosis (MS) reported substantial differences in PIRA incidence and persistence depending on definition parameters.The study suggests that a proposed standardized definition could improve consistency and comparability across future MS research.1
Overall, the analysis comprised 33,303 patients with clinically definite relapsing-remitting MS from 186 centers in 43 countries, drawn from a total pool of 87,239 patients in the MSBase registry between July 2004 and July 2023.2 Conducted by lead author Jannis Müller, MD, MSc, former research fellow of the CORe team at the RMH Neuroimmunology Centre in Melbourne, and colleagues, patients included in the analysis had an average of 15.1 visits across 8.9 years, and 84.2% were diagnosed with relapsing-remitting MS.
Investigators tested PIRA incidence and persistence using combinations of criteria such as baseline disability, confirmation period, magnitude of worsening, and freedom from relapse at both worsening and confirmation time points. Across all definitions, researchers reported that PIRA incidence ranged from 0.141 to 0.658 events per decade, and persistence ranged from 0.753 to 0.919 over at least 5 years.
“PIRA is an emerging concept in MS, which is becoming increasingly more important. This is because the contemporary therapies are very effective at reducing the risk of MS relapses, but less so at reducing progression of disability. To quantify how much disability in MS is attributable to relapses and how much is [because of] PIRA is important for development of new therapies and correct use of the current therapies,” Tomas Kalincik, MD, PhD, professor of neurology and applied statistician at University of Melbourne and Royal Melbourne Hospital, told NeurologyLive® in a recent interview. “For example, a new class of therapies – BTK-inhibitors – seem to be more effective at reducing progression than the risk of relapses. If that impression proves to be correct, then we should know who has developed disability in the absence of relapses and whether we can prevent such disability in the future.”
