Equal impact of high- and moderate-efficacy therapies on PIRMA

High-efficacy therapies (HET) were associated with superior control of relapse-related disability accumulation when used first-line compared with moderate-efficacy treatments (MET) in a French registry study. However, the results also suggested that HET were linked to a relatively higher risk of progression independent of relapses and MRI activity (PIRMA).

HET improve the long-term prognosis of patients with relapsing-remitting MS (RRMS) by significantly reducing inflammatory disease activity. Yet, their effect on disability mechanisms unrelated to new lesion formation remains unclear, noted Dr Laure Michel (Rennes University Hospital, France). Dr Michel and colleagues evaluated the real-world impact of HET versus MET on ‘pure’ disability progression [1]. The cohort comprised 10,499 RRMS participants who initiated HET (n=2,666) or MET (n=7,833) between 2010 and 2023. The primary endpoint was time to first PIRMA. The mean age at MS onset was 36.4 years (SD 10.3), and the mean follow-up time was 3.7 years (SD 2.5).

A slightly but statistically significantly longer time to first PIRMA was observed in the MET group compared with the HET group: restricted mean survival time (RMST) 8.9 years versus 8.7 years; P=0.049). After 10 years, 24.2% (95% CI 19.4-30.0) of HET participants had reached PIRMA compared to 21.6% (95% CI 18.8-24.1) of MET participants (HR 1.34; 95% CI 1.23-1.71). The adjusted incidence rate ratio of PIRMA was 1.26 (95% CI 1.22-1.72).

By contrast, the time to first confirmed disease progression (CDP) was significantly longer in the HET group compared to the MET group: 7.6 vs 7.3 years (P=0.003). According to Dr Michel, this was likely related to the shorter time to first relapse-associated worsening (RAW) in the MET group (8.8 vs. 9.2 years; P<0.001). The time to first progression, independent of relapse activity (PIRA), was identical in both groups at 8.3 years (P=0.7).

Baseline risk factors associated with increased PIRMA risk included higher EDSS scores, spinal cord lesions, >9 T2 lesions on brain MRI, and the absence of gadolinium-enhancing lesions.

Dr Michel concluded that the higher PIRMA risk associated with HET may reflect its limited impact on disability mechanisms, independent of lesion formation.

1. Laure M, et al. Progression independent of relapse and MRI activity and treatment strategy in the French MS registry. O048, ECTRIMS 2025 Congress, 24-26 September  2025, Barcelona, Spain.

Medical writing support was provided by Michiel Tent.

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Posted on 30 September 2025