| Contributors: |
E, Portaccio; M, Betti; E, De Meo; L, Pastò; E, Prestipino; A, Lugaresi; E, Cocco; G, De Luca; F, Patti; Clerici Vlam, Torri; D, Ferraro; V, Brescia Morra; G, Salemi; M, Vianello; R, Cerqua; M, Inglese; Mb, Pasanisi; P, Perini; S, Romano; C, Pozzilli; C, Tortorella; A, Di Sapio; P, Annovazzi; M, Simone; P, Iaffaldano; Ma, Rocca; M, Filippi; M, Trojano; Mp, Amato; Gajofatto, Alberto; Protti, Alessandra; Leone, Alessandro; Chiara Landi, Anna; Luisa Ancona, Anna; Marson, Annamaria; Conte, Antonella; Giordano, Antonio; Gallo, Antonio; Bonaventura, Ardito; Rini, Augusto; Marini, Bruno; Avolio, Carlo; Piantadosi, Carlo; Chiavazza, Carlotta; Solaro, Claudio; Fioretti, Cristina; Cargnelutti, Daniela; De Pascalis, Daniela; Nasielli, Davide; Vecchio, Domizia; Sessa, Edoardo; Colombo, Elena; Cartechini, Elisabetta; Milano, Eva; Marinelli, Fabiana; Capone, Fioravante; De Robertis, Francesca; Matta, Francesca; Corea, Francesco; D'Andrea, Francesco; Passantino, Francesco; Granella, Franco; Turano, Gabriella; Lus, Giacomo; Brichetto, Giampaolo; Teresa Maniscalco, Giorgia; Cerullo, Giovanni; Alessandra Marfia, Girolama; Ribizzi, Giuseppe; Santuccio, Giuseppe; Trivelli, Giuseppe; Cavaletti, Guido; Roberto Zarbo, Ignazio; Pesci, Ilaria; Plewnia, Katrin; Sinisi, Leonardo; Pasquali, Livia; Capone, Lorenzo; Mancinelli, Luca; Massacesi, Luca; E Grimaldi, Luigi M; Zuliani, Luigi; Capobianco, Marco; Peresson, Marco; Rovaris, Marco; Buccafusca, Maria; Gabriella Coniglio, Maria; Grazia Celani, Maria; Grazia Grasso, Maria; Luisa Piras, Maria; Merello, Maria; Teresa Ferrò, Maria; Rodegher, Mariaemma; Fortunato, Marianna; Clerico, Marinella; Falcini, Mario; Santangelo, Mario; Bianchi, Marta; Mirabella, Massimiliano; Foschi, Matteo |
| Description: |
Objectives: Progression independent of relapse activity (PIRA) is the main driver of disability accumulation in relapsing multiple sclerosis (MS). We tested various PIRA definitions against the risk of long-term disability. Methods: Patients with relapsing MS, first visit ≥January 1, 2000, ≥3 visits with Expanded Disability Status Scale (EDSS), and ≥5-year follow-up were extracted from the Italian MS and Related Disorders Register on September 29, 2023. Eighteen PIRA definitions were obtained combining fixed or roving baseline, 24-week, 48-week confirmed or sustained disability accrual, no relapses ≤90 days before/≤30 days after the event (90d), ≤180 days before/≤30 days after the event, or absence of relapses from baseline to confirmation score (ABS). Predictive performance against the reaching of EDSS = 6.0 was calculated. Results: A total of 30,203 patients were included. After a follow-up of 11.3 ± 4.3 years, PIRA ranged from 38.8% to 74.1%. EDSS = 6.0 was detected in 4,401 (15%) patients. Sensitivity of PIRA definitions against EDSS = 6.0 was higher using the 90d criterion (66.7%-69.4%), while the ABS criterion increased specificity (55.3%-62.2%). Discussion: The definition of PIRA combining roving baseline, no relapses 90 days before and 30 days after the event and 24-week confirmation achieved the best predictive value and feasibility, supporting its use in routine practice and research. |