So we are on our way to the Late Breaking Abstracts as the show stopper for ECTRIMS….Now that we have had our fill of animal models and Sid had choked on his cornflakes we can get down to the serious stuff. So off to progression and the first one to catch my eye is a subject that I have been banging on about and that PIRA is a great idea that has been butchered to sell the idea of DMT targeting progression that is not the same as the mechanism driving relapse. I have suggested that the way it is being done is a composite and is to a significant part influenced by the processes that drive relapsing disease.
We have had the imagers telling us that PIRA is detecting smouldering MS…the “real MS” that drives progression. This stuff from Italy reports that typical inflammatory lesions account for most of the smouldering lesions….So sadly PIRA papers need to reflect on what they are actually measuring…sadly a nice concept as there are in my mind distinct processes driving progression but they are are interlinked with inflammatory disease dribling lesions and relapses….so a nice idea destroyed by marketeers and neuros trying to flog drugs (My opinion only). Therefore, be careful in what you take from these types of presentations
Abstract Number: 1342/P559 Abstract Number: 1342/P559
Progression independent of relapse activity in relapsing multiple sclerosis is less smoldering than it seems Progression independent of relapse activity in relapsing multiple sclerosis is less smoldering than it seems
Emilio Portaccio et al.
Introduction: The identification of progression independent of relapse activity (PIRA), the most important contributor of disability accrual in relapsing multiple sclerosis (MS), can be affected by visit frequency, granularity of assessment tools and availability of imaging and fluid biomarkers of disease activity.
Objectives/Aims: Objectives/Aims: Methods: To assess the impact of visit frequency and regular magnetic resonance imaging (MRI) monitoring on the identification of Expanded Disability Status Scale (EDSS)-based PIRA in patients with relapsing MS.
Methods: In this multicentric, retrospective, cohort study based on prospectively acquired data from the Italian Multiple Sclerosis Register, inclusion criteria were: diagnosis of Clinically Isolated Syndrome or relapsing-remitting MS, first visit on or after January 1, 2000, at least 3 Expanded Disability Status Scale (EDSS) evaluations, at least 5 years of follow-up. PIRA was defined as a 24-week confirmed disability accrual (CDA: EDSS increase of 1.5 points if baseline EDSS=0; 1.0 point if EDSS>1.0 and < 5.5; 0.5 point if EDSS>5.5) with roving baseline and absence of relapses < 90 days before and < 30 days after the onset of both CDA and confirmation visit. The same definition was applied in the subgroup of patients with at least 1 visit every year and in patients with at least 1 brain and/or spinal cord MRI every year.
Results: The whole sample included 30203 relapsing MS patients followed-up for 11.3+ 4.3 years. A first CDA wasobserved in 18187 (60.2%) patients. PIRA accounted for 12501 (68.7%) events. In 5434 patients with at least 1 visit every year, CDA occurred in 3146 (57.9%) subjects. Again, PIRA accounted for 2223 (70.7%) events. Focusing on 605 patients with annual MRI examinations, 357 (59%) CDA occurred. The proportion of PIRA decreased from 63.6% (227) to 45.1% (161) due to the inclusion of active MRI (new/enlarging T2 lesions and/or gadolinium enhancing lesions) close to the event in the PIRA definition.
Conclusion: While visit frequency does not affect PIRA detection, the availability of regular MRI monitoring significantly impacts on the classification of disability accumulation phenotype. One third of EDSS-based PIRA events were underpinned by traditional focal inflammatory activity at brain/spinal cord MRI. Further studies are needed to clarify whether smoldering MS has been overestimated or should be unveiled through more granular assessments.
Then we can have another poster questioning PIRA value
Abstract Number: 670/P569 Abstract Number: 670/P569
Progression independent of relapsing biology in multiple sclerosis: a real-word study Progression independent of relapsing biology in multiple sclerosis: a real-word study
Heather Yong et al.
Introduction: Recent literature suggests relapsing-remitting MS (RRMS) patients acquired disability through either relapseassociated worsening, or progression independent of relapse activity (PIRA). PIRA implies the existence of “progressive biology” in RRMS and is a paradigm shifting concept suggesting MS exists on a continuum with progression from disease onset. Mechanistically/biologically PIRA could impact the traditional distinction between progressive and relapsing-MS.
Objectives/Aims: Objectives/Aims: Herein, we aimed to isolated “relapsing biology” in MS in a real-world cohort using a modified criterion termed progression independent of relapsing biology (PIRB). Methods: Methods: PIRB was defined as disability progression and exclusion of (a) relapses, (b) inflammatory MRI activity, (c)interim disability worsening/improvement over the observation period, and (d) progression secondary to alternative causes (including formal secondary-progressive MS conversion). Disability progression was defined as an increase on the expanded disability status scale (EDSS) of ≥1.5 (if baseline EDSS was 0); ≥1 (if baseline EDSS was 0.5–5.5); or ≥0.5 (if baseline EDSS was >5.5). This framework was applied to 701 RRMS participants at the Calgary, Canada MS clinic on dimethyl fumarate, fingolimod, or ocrelizumab. A secondary outcome was PIRB in a clinical trial cohort of participants with clinically isolated syndrome on minocycline (n=122).
Results: In the dimethyl fumarate (n=160), fingolimod (n=245), ocrelizumab (n=296), and minocycline (n=122) cohorts 26.25% (n=42), 30.20% (n=74), 14.86% (n=44), and 14.1% (n=20) of participants experienced disability progression over an observation period from 2011–2024. PIRB was rare and rates were consistent across therapies (3.75% dimethyl fumarate, 3.67% fingolimod, 3.72% ocrelizumab, and 3.52% minocycline). PIRB participants tended to be female, older at disease onset (p=0.029 compared to all participants) and trended towards a longer disease duration.
Conclusion: PIRB is rare and occurs at a consistent rate (in real-world and clinical trial cohorts) despite varied rates of disability progression. PIRB may offer a practical alternative to PIRA to inform biologic/phenotypic categorization in MS.
COI None
Disclaimer My view alone
Source: multiple-sclerosis-research.org