Patients with multiple sclerosis (MS) who have progression independent of relapse activity (PIRA) after their first demyelinating attack were more likely to experience poorer long-term outcomes than those without PIRA. These are the findings of a study published in JAMA Neurology.
The 2 main mechanisms of disability accumulation in MS are PIRA and relapse-associated worsening (RAW). In general, PIRA has been found to be a predominant component in neurogenerative disease. To date, it remains unclear what factors predict PIRA and what the comparative outcomes are.
To better study the causes and consequences of PIRA, researchers sourced data for this study from the Multiple Sclerosis Center of Catalonia in Barcelona, Spain, which were collected after a patient’s first demyelinating attack occurring between January 1994 and July 2021. The primary outcome was the time to an Expanded Disability Status Scale (EDSS) score of 6.0.
The study included 1128 patients who were mean age, 32.1 (standard deviation [SD], 8.3) years during their first attack, and 69.2% were women. The first attack affected the optic nerve (34.1%), spinal cord (29.5%), brainstem (25.1%), or other (10.7%). A total of 26.0% patients had no T2 lesions, and 64.0% had no spinal cord lesions.
During a median follow-up time of 10.46 years, 277 patients had PIRA at a median of 7.22 years. Among patients with PIRA, 86 had early PIRA at a median of 3.8 years and 191 had late PIRA at 10.1 years. In addition, 73 patients experienced active PIRA and 71 nonactive PIRA.
In general, PIRA associated with more T2 lesions (P =.03) but not more spinal cord lesions (P =.11).
The adjusted increased EDSS score was 0.04 (95% CI, 0.02-0.05) points per year among patients without PIRA compared with 0.18 (95% CI, 0.16-0.20; P <.001) points for patients with PIRA. Among patients with PIRA, those with early PIRA had greater increases in EDSS scores than late PIRA (mean, 0.31 vs 0.13 points per year; P <.001) as did patients with active PIRA compared with nonactive PIRA (mean, 0.20 vs 0.12 points per year; P =.05), respectively.
The proportion of patients reaching EDSS 6.0 at 20 years was higher among those with PIRA than without PIRA (18.49% vs 2.45%; P <.001) and those with active PIRA compared with nonactive PIRA (38.32% vs 10.46%; P =.003), respectively.
In adjusted analyses, reaching confirmed EDSS 6.0 was significantly associated with PIRA (adjusted hazard ratio [aHR], 7.93; 95% CI, 2.25-27.96; P =.001) and early PIRA compared with late PIRA (aHR, 26.21; 95% CI, 2.26-303.95; P =.009).
The only significant predictor for PIRA was older age (hazard ratio [HR], 1.43; 95% CI, 1.23-1.65 per decade; P <.001).
This study may have been limited, as systematic spinal cord magnetic resonance imaging (MRI) scans were not done before 2007.
These data indicated that PIRA was common among patients with MS after first demyelinating attack and associated with nonreversible, long-term disability.
The researchers concluded, “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.”
Additional study into identifying predictors for PIRA are needed.
Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.
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. Published online December 19, 2022. doi:10.1001/jamaneurol.2022.4655