| Contributors: |
Haggiag, S.; Prosperini, L.; Filippi, M.; Rocca, M. A.; Iaffaldano, P.; Patti, F.; Inglese, M.; Borriello, G.; Totaro, R.; Lus, G.; Fantozzi, R.; Brescia Morra, V.; Romano, S.; Frau, J.; Marfia, G. A.; Maniscalco, G. T.; Amato, M. P.; Di Sapio, A.; De Luca, G.; Crisafulli, S. G.; Curti, E.; Foschi, M.; Cavalla, P.; Salemi, G.; Conte, A.; Valentino, P.; Ferraro, D.; Lugaresi, A.; Realmuto, S.; Perini, P.; Ferraro, E.; Montepietra, S.; Avolio, C.; Vianello, M.; Gazzola, P.; Marinelli, F.; Pasquali, L.; Bucello, S.; Vecchio, D.; Protti, A.; Sangalli, F.; Rovaris, M.; Grimaldi, L.; De Riz, M.; Barone, P.; Scarano, V.; Ardito, B.; Sinisi, L.; Immovilli, P.; Pesci, I.; Colombo, E.; Capobianco, M. A.; Fioretti, C.; Coniglio, M. G.; Giordano, A.; Tassinari, T.; Cargnelutti, D.; Matta, F.; Falcini, M.; Gatto, M.; Mascoli, N.; Balgera, R.; Sessa, E.; Iodice, R.; Solaro, C.; Plewnia, K.; Santangelo, M.; Barcella, V.; Ferro, M. T.; Sica, F.; Cerqua, R.; Santuccio, G.; Corea, F.; Leone, A.; Nasuelli, D.; Rini, A. M.; Brichetto, G.; Cottone, S.; Ulivelli, M.; Pizzorno, M.; Rossi, P.; Milano, E.; Zuliani, L.; Ruggieri, S.; Gasperini, C.; Trojano, M.; Tortorella, C. |
| 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 ... |