Progression independent of relapse and MRI activity and treatment strategies in multiple sclerosis

Abstract The impact of high-efficacy therapies (HET) on progression independent of relapse and MRI activity (PIRMA) remains poorly defined. In this context, using the French MS registry, we aimed to assess the real-life effectiveness of HET compared with moderate efficacy therapies (MET) on PIRMA in relapsing-onset MS (RMS) patients. Data were collected from RMS patients of the French MS Registry, between January, 2010 and June, 2023, with a mean follow-up of 3.7 years. RMS patients were included in the analysis if they were treated first with HET (2666 included) or MET (7833 included), and had EDSS and MRI follow-up every two years. Each outcome was studied using a propensity score framework. The primary outcome was time-to-first PIRMA. Secondary outcomes were PIRMA incidence, time-to-first confirmed disability progression (CDP), relapse-associated worsening (RAW), MRI-associated worsening (MAW) and identification of risk factors associated with PIRMA. A total of 10499 patients fulfilled the inclusion criteria. The mean (SD) age at treatment initiation was 36.4 (10.3) years, with a mean (SD) disease duration of 3.1 (5.1) years. The restricted mean survival (SD) time to first PIRMA was slightly significantly shorter in the HET group compared to the MET group (8.7 yrs (0.08) vs. 8.9 yrs (0.05) p=0.017). However, when looking at time-to-first CDP, it tend to be longer in the HET group compared to the MET group (7.6 (0.10) vs. 7.3 years (0.06); p=0.071), and it was probably linked to the shorter time-to-first RAW and MAW in the MET group (9.2 (0.06) vs 8.7 years (0.05); p0.001 for RAW and 9.0 (0.05) vs 8.5 (0.07); p0.001 for MAW). Baseline risk factors associated with increased PIRMA incidence in the whole population were: high EDSS, higher age at baseline and the presence of spinal cord lesions. Even if HET have a better control on disability accumulation related to disease activity than MET, our real-life study suggests that PIRMA-related mechanisms are not differentially affected by HET versus MET.