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Standardized Definition of Progression Independent of Relapse Activity (PIRA) in Relapsing-Remitting Multiple Sclerosis.

Title: Standardized Definition of Progression Independent of Relapse Activity (PIRA) in Relapsing-Remitting Multiple Sclerosis.
Authors: Müller, Jannis; Sharmin, Sifat; Lorscheider, Johannes; Ozakbas, Serkan; Karabudak, Rana; Horakova, Dana; Weinstock-Guttman, Bianca; Shaygannejad, Vahid; Etemadifar, Masoud; Alroughani, Raed; Patti, Francesco; Eichau, Sara; Prat, Alexandre; Lugaresi, Alessandra; Tomassini, Valentina; Kermode, Allan G; Amato, Maria Pia; Turkoglu, Recai; Altintas, Ayse; Buzzard, Katherine; Soysal, Aysun; van der Walt, Anneke; Butzkueven, Helmut; Blanco, Yolanda; Gerlach, Oliver; Khoury, Samia J; Barnett, Michael; John, Nevin; Lechner-Scott, Jeannette; Foschi, Matteo; Surcinelli, Andrea; Van Pesch, Vincent; Prevost, Julie; Sa, Maria Jose; Maimone, Davide; D'hooghe, Marie; Hughes, Stella; Hodgkinson, Suzanne; McGuigan, Chris; Cartechini, Elisabetta; Taylor, Bruce; Spitaleri, Daniele; Slee, Mark; McCombe, Pamela; Yamout, Bassem; Benkert, Pascal; Kuhle, Jens; Kappos, Ludwig; Roos, Izanne; Kalincik, Tomas; MSBase Study Group; Havrdova, Eva Kubala; Girard, Marc; Duquette, Pierre; Fabis-Pedrini, Marzena; Carroll, William M; Skibina, Olga; Gouider, Riadh; Mrabet, Saloua; Ramo-Tello, Cristina; Solaro, Claudio; Habek, Mario; Van Wijmeersch, Bart; Ampapa, Radek; Macdonell, Richard; Oreja-Guevara, Celia; de Gans, Koen; Laureys, Guy; Oh, Jiwon; Garber, Justin; Gray, Orla; Agüera-Morales, Eduardo; Sanchez-Menoyo, Jose Luis; Castillo-Triviño, Tamara; Grigoriadis, Nikolaos; Petersen, Thor; Hardy, Todd A; Vucic, Steve; Reddel, Stephen; Ramanathan, Sudarshini; Al-Asmi, Abdullah; Simu, Mihaela; Baghbanian, Seyed Mohammad; Poehlau, Dieter; Al-Harbi, Talal; Rojas, Juan Ignacio; Deri, Norma; Lalive, Patrice; Cambron, Melissa; Csepany, Tunde; Shuey, Neil; Willekens, Barbara; Shaw, Cameron; Decoo, Danny; Massey, Jennifer; Yaldizli, Özgür; Derfuss, Tobias; Granziera, Cristina
Contributors: UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire; UCL - (SLuc) Service de neurologie
Source: JAMA neurology, Vol. 82, no.6, p. 614-625 (2025)
Publisher Information: American Medical Association
Publication Year: 2025
Collection: DIAL@USL-B (Université Saint-Louis, Bruxelles)
Subject Terms: Humans; Multiple Sclerosis; Relapsing-Remitting; Female; Male; Disease Progression; Adult; Retrospective Studies; Recurrence; Disability Evaluation; Middle Aged; Registries; Cohort Studies
Description: IMPORTANCE: Progression independent of relapse activity (PIRA) is a significant contributor to long-term disability accumulation in relapsing-remitting multiple sclerosis (MS). Prior studies have used varying PIRA definitions, hampering the comparability of study results. OBJECTIVE: To compare various definitions of PIRA. DESIGN, SETTING, AND PARTICIPANTS: This cohort study involved a retrospective analysis of prospectively collected data from the MSBase registry from July 2004 to July 2023. The participants were patients with MS from 186 centers across 43 countries who had clinically definite relapsing-remitting MS, a complete minimal dataset, and 3 or more documented Expanded Disability Status Scale (EDSS) assessments. EXPOSURE: Three-hundred sixty definitions of PIRA as combinations of the following criteria: baseline disability (fixed baseline with re-baselining after PIRA, or plus re-baselining after relapses, or plus re-baselining after improvements), minimum confirmation period (6, 12, or 24 months), confirmation magnitude (EDSS score at/above worsening score or at/above threshold compared with baseline), freedom from relapse at EDSS score worsening (90 days prior, 90 days prior and 30 days after, 180 days prior and after, since previous EDSS assessment, or since baseline), and freedom from relapse at confirmation (30 days prior, 90 days prior, 30 days before and after, or between worsening and confirmation). MAIN OUTCOME AND MEASURE: For each definition, we quantified PIRA incidence and persistence (ie, absence of a 3-month confirmed EDSS improvement over ≥5 years). RESULTS: Among 87 239 patients with MS, 33 303 patients fulfilled the inclusion criteria; 24 152 (72.5%) were female and 9151 (27.5%) were male. At the first visits, the mean (SD) age was 36.4 (10.9) years; 28 052 patients (84.2%) had relapsing-remitting MS, and the median (IQR) EDSS score was 2.0 (1.0-3.0). Participants had a mean (SD) 15.1 (11.9) visits over 8.9 (5.2) years. PIRA incidence ranged from 0.141 to 0.658 events per decade and ...
Document Type: article in journal/newspaper
Language: English
Relation: boreal:302330; http://hdl.handle.net/2078.1/302330; info:pmid/40227706
DOI: 10.1001/jamaneurol.2025.0495
Availability: http://hdl.handle.net/2078.1/302330; https://doi.org/10.1001/jamaneurol.2025.0495
Rights: info:eu-repo/semantics/openAccess
Accession Number: edsbas.7029CAA
Database: BASE