| Contributors: |
Haggiag, Shalom; Prosperini, Luca; Filippi, Massimo; Rocca, Maria A.; Iaffaldano, Pietro; Patti, Francesco; Inglese, Matilde; Borriello, Giovanna; Totaro, Rocco; Lus, Giacomo; Fantozzi, Roberta; Brescia Morra, Vincenzo; Romano, Silvia; Frau, Jessica; Marfia, Girolama Alessandra; Maniscalco, Giorgia Teresa; Amato, Maria Pia; Di Sapio, Alessia; De Luca, Giovanna; Crisafulli, Sebastiano Giuseppe; Curti, Erica; Foschi, Matteo; Cavalla, Paola; Salemi, Giuseppe; Conte, Antonella; Valentino, Paola; Ferraro, Diana; Lugaresi, Alessandra; Realmuto, Sabrina; Perini, Paola; Ferraro, Elisabetta; Montepietra, Sara; Avolio, Carlo; Vianello, Marika; Gazzola, Paola; Marinelli, Fabiana; Pasquali, Livia; Bucello, Sebastiano; Vecchio, Domizia; Protti, Alessandra; Sangalli, Francesca; Rovaris, Marco; Grimaldi, Luigi; De Riz, Milena; Barone, Paolo; Scarano, Valentina; Ardito, Bonaventura; Sinisi, Leonardo; Immovilli, Paolo; Pesci, Ilaria; Colombo, Elena; Capobianco, Marco Alfonso; Fioretti, Cristina; Coniglio, Maria Gabriella; Giordano, Antonello; Tassinari, Tiziana; Cargnelutti, Daniela; Matta, Francesca; Falcini, Mario; Gatto, Maurizia; Mascoli, Nerina; Balgera, Roberto; Sessa, Edoardo; Iodice, Rosa; Solaro, Claudio; Plewnia, Katrin; Santangelo, Mario; Barcella, Valeria; Ferrò, Maria Teresa; Sica, Francesco; Cerqua, Raffaella; Santuccio, Giuseppe; Corea, Francesco; Leone, Alessandro; Nasuelli, Davide; Rini, Augusto Maria; Brichetto, Giampaolo; Cottone, Salvatore; Ulivelli, Monica; Pizzorno, Matteo; Rossi, Patrizia; Milano, Eva; Zuliani, Luigi; Ruggieri, Serena; Gasperini, Claudio; Trojano, Maria; Tortorella, Carla |
| Description: |
Importance: Early treatment choice in relapsing-remitting multiple sclerosis (RRMS) is prognostically crucial, yet robust comparative data on cladribine vs sphingosine-1-phosphate receptor modulators (S1PRMs) in treatment-naive patients with RRMS are limited. Objective: To compare the clinical effectiveness of cladribine vs S1PRMs in treatment-naive individuals with RRMS. Design, setting, and participants: This comparative effectiveness research study used data from 108 Italian multiple sclerosis (MS) centers affiliated with the Italian Multiple Sclerosis and Related Disorders Register. All treatment-naive patients with RRMS who initiated cladribine or an S1PRM (fingolimod, ozanimod, or ponesimod) between January 2011 and October 2021 and had at least 12 months of follow-up were included. Propensity score matching and pairwise censoring were used to balance baseline differences and follow-up duration. Patient data were extracted from the register in September 2024. Exposure: Initiation of cladribine or an S1PRM, with duration reflecting clinical practice. Main outcomes and measures: The primary outcome was no evidence of disease activity (NEDA-3) and its subcomponents. Secondary analyses evaluated disability accrual subdivided into progression independent of relapse activity (PIRA) and relapse-associated worsening (RAW), plus variables associated with treatment response. Cox proportional hazards models, adjusted for visit and magnetic resonance imaging (MRI) frequency, were used to compare outcomes. Results: Of the 1587 patients (485 taking cladribine and 1102 taking S1PRMs), matching yielded 475 pairs (950 individuals; mean [SD] age, 34.7 [10.7] years; 686 female [72.2%]), with a median (IQR) follow-up period of 25 (12-60) months. For the cladribine vs S1PRM groups, no significant differences were observed in relapse rates (72 patients [15.2%] vs 76 patients [16.0%]), MRI activity (137 patients [31.3%] vs 145 patients [34.8%]), or NEDA-3 loss (194 patients [44.4% vs 219 patients [52.2%]). Cladribine was ... |