Risk factors and importance of persistent PIRA

Sustained disability progression independent of relapse activity (PIRA) increased the risk of severe disability and secondary progressive MS (SPMS) by a factor of 4 or 5. However, PIRA is not the same as early SPMS, as one-third of relapsing-remitting MS patients showed a confirmed improvement of the Expanded Disability Status Scale (EDSS) after PIRA.

Researchers studied the factors associated with persistence or improvement after PIRA, as well as the effects of PIRA persistence on long-term outcomes in MS [1]. PIRA can be a sign of early SPMS, but PIRA events may regress over time. A cohort study was set up using data from 4,713 patients with relapsing-remitting MS who were enrolled in the MSBase registry between April 1995 and January 2024. One of the inclusion criteria was a minimum of 1 PIRA event, defined as 6-month confirmed disability progression (CDP) without relapse. The primary outcome was time to 6-month confirmed improvement after PIRA.

After a median follow-up of 6.8 years, the primary endpoint was met by almost a third of the investigated patients (n=1,507; 32%). When matched with patients with persistent PIRA (n=3,206) in a multivariate analysis, younger age (HR 0.98; 95% CI 0.98–0.99; P<0.0001), lower EDSS at baseline (HR 0.74; 95% CI 0.69–0.78; P<0.0001), and high-efficacy DMT use at baseline (HR 1.22; 95% CI 1.08–1.38; P<0.0015) were significantly associated with improvement after PIRA.

Investigated patients with persistent PIRA were at a substantially higher risk of reaching EDSS 6 and SPMS, compared with non-persistent PIRA: the HR was 5.19 (95% CI 4.05–6.67; P<0.0001) for reaching EDSS 6, and 3.51 (95% CI 2.42–5.08; P<0.0001) for reaching SPMS.

1. Zhu C, et al. Risk factors associated with persistent progression independent of relapse activity (PIRA), and the association of persistent PIRA with disability progression in multiple sclerosis. Abstract O055, ECTRIMS 2024, 17–20 October 2024, Copenhagen, Denmark.

Medical writing support was provided by Michiel Tent

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Posted on 24 September 202424 September 2024