In MS, Early Progression Independent of Relapse Activity Suggests Unfavorable Prognosis

Patients with progression independent of relapse activity (PIRA) within 5 years of multiple sclerosis diagnosis had a 26-fold higher risk of developing severe disability compared with patients with PIRA late in the disease, according to study results published in JAMA Neurology.

“Results suggest that presenting with PIRA after a first demyelinating event in multiple sclerosis is an ominous prognosis, especially if it occurs early in the disease course,” wrote corresponding author Carmen Tur, MD, PhD, of the Hospital Universitari Vall d’Hebron, Barcelona, Spain, and coauthors.

The cohort study included 1128 patients from the Multiple Sclerosis Center of Catalonia in Spain. Participants had a first demyelinating event from multiple sclerosis that occurred between January 1, 1994, and July 31, 2021. Among them, 25% developed a first PIRA event over a median follow-up of 7.2 years: 31% had early PIRA, and 51% had active PIRA.

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According to the study, patients with PIRA were slightly older, more prone to having brain lesions, and were more likely to have oligoclonal bands in cerebrospinal fluid than patients without PIRA. The sole predictor of PIRA among participants was older age at the first attack.

Annual Expanded Disability Status Scale (EDSS) increases were steeper among patients with PIRA, the study found. Patients with PIRA also showed an 8-fold higher risk of reaching 6-month confirmed EDSS 6.0 from the first demyelinating event compared with patients without PIRA.

Specifically among patients with PIRA, annual EDSS increases were higher for those with early PIRA compared with late PIRA. Researchers reported a 26.21 hazard ratio of reaching EDSS 6.0 with early PIRA.

“Results of this cohort study suggest that PIRA is essentially a nonreversible phenomenon associated with unfavorable long-term disability outcomes, especially if such PIRA events occur early in the disease course,” researchers wrote. “Identifying all who will develop PIRA as soon as possible after the first demyelinating event, especially early PIRA, may lead to better treatment choices, and subsequently, better long-term outcomes.”

Reference

Tur C, Carbonell-Mirabent P, Cobo-Calvo Á, et al. Association of early progression independent of relapse activity with long-term disability after a first demyelinating event in multiple sclerosis. JAMA Neurol. 2023;80(2):151-160. doi:10.1001/jamaneurol.2022.4655