Progression Independent of Relapse Activity in Multiple Sclerosis
Closer to Solving the Pathologic Puzzle
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Progression independent of relapse activity (PIRA) is one of the main mechanisms of disability accrual in multiple sclerosis (MS) even in people with relapsing-remitting MS (RRMS).1 PIRA can occur at any stage of the disease and is associated with unfavorable long-term outcomes, especially if PIRA occurs early in the disease course.2 The pathologic substrates of PIRA are not yet well understood, although there is growing evidence suggesting that PIRA may occur mainly in a predominant neurodegenerative context,3-6 sometimes in combination with an acute inflammatory activity.2,5 A deeper understanding of the pathologic processes underlying PIRA represents a vital initial stride toward averting the accumulation of irreversible disability in MS.
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© 2023 American Academy of Neurology.
Publication History
Received: July 27, 2023
Accepted: August 24, 2023
Published online: December 13, 2023
Published in issue: January 9, 2024
Disclosure
C. Tur has received honoraria from Roche and Novartis and is a steering committee member of the of the O'HAND trial and of the Consensus group on Follow-on DMTs. She is also currently being funded by a Junior Leader La Caixa Fellowship (fellowship code is LCF/BQ/PI20/11760008), awarded by "la Caixa" Foundation (ID 100010434). She has also received the 2021 Merck's Award for the Investigation in MS, awarded by Fundación Merck Salud (Spain). In 2015, she received an ECTRIMS Postdoctoral Research Fellowship and has received funding from the UK MS Society; M.A. Rocca received consulting fees from Biogen, Bristol Myers Squibb, Eli Lilly, Janssen, and Roche and speaker honoraria from AstraZeneca, Biogen, Bristol Myers Squibb, Bromatech, Celgene, Genzyme, Horizon Therapeutics Italy, Merck Serono SpA, Novartis, Roche, Sanofi, and Teva. She receives research support from the MS Society of Canada, the Italian Ministry of Health, and Fondazione Italiana Sclerosi Multipla. She is an Associate Editor for Multiple Sclerosis and Related Disorders. Go to Neurology.org/N for full disclosures.
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Cited By
- Development of Early Progression Independent of Relapse Activity significantly impacts on Disability Accumulation in Patients with Multiple Sclerosis, Multiple Sclerosis and Related Disorders, (106529), (2025).https://doi.org/10.1016/j.msard.2025.106529
- Advancements in multiple sclerosis, Internal Medicine Journal, (2025).https://doi.org/10.1111/imj.70023
- Novel Cell Models to Study Myelin and Microglia Interactions, International Journal of Molecular Sciences, 26, 5, (2179), (2025).https://doi.org/10.3390/ijms26052179
- A Window into New Insights on Progression Independent of Relapse Activity in Multiple Sclerosis: Role of Therapies and Current Perspective, International Journal of Molecular Sciences, 26, 3, (884), (2025).https://doi.org/10.3390/ijms26030884
- Ofatumumab for multiple sclerosis with disability accumulation, Journal of the Neurological Sciences, 468, (123356), (2025).https://doi.org/10.1016/j.jns.2024.123356
- Barriers in Healthcare to the Use of Optical Coherence Tomography Angiography in Multiple Sclerosis, Neurology and Therapy, 14, 1, (45-56), (2024).https://doi.org/10.1007/s40120-024-00670-1
- Rituximab in secondary progressive multiple sclerosis: a meta‐analysis, Annals of Clinical and Translational Neurology, 11, 10, (2707-2718), (2024).https://doi.org/10.1002/acn3.52186
- Continuous diffuse brain atrophy independent of relapse as a hallmark of multiple sclerosis beginning from relapsing-remitting stage, Clinical Neurology and Neurosurgery, 242, (108342), (2024).https://doi.org/10.1016/j.clineuro.2024.108342
- The global patient-reported outcomes for multiple sclerosis initiative: bridging the gap between clinical research and care – updates at the 2023 plenary event, Frontiers in Neurology, 15, (2024).https://doi.org/10.3389/fneur.2024.1407257
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