Profiling the long-term risk of severe adverse events in a cohort of multiple sclerosis patients treated with different treatment sequences: Results from the Italian Multiple Sclerosis and Related Disorders Registry (I-MS&RD) (ProSA study).

Authors

Damiano Paolicelli, Giuseppe Lucisano, Alessia Manni, Pietro Iaffaldano, Marta Simone, Antonio Iaffaldano, Tommaso Guerra, Vincenzo Mangialardi, Francesco Patti, Eleonora Cocco, Giovanna De Luca, Pietro Annovazzi, Paolo Ragonese, Carlo Pozzilli, Matilde Inglese, Paola Perini, Claudio Gasperini, Carla Tortorella, Girolama Alessandra Marfia, Diana Ferraro, Giacomo Lus, Marika Vianello, Maria Assunta Rocca, Antonella Conte, Silvia Romano, Vincenzo Brescia Morra, Alessandra Lugaresi, Alessia Di Sapio, Clara Grazia Chisari, Raffaella Cerqua, Umberto Aguglia, Ilaria Pesci, Carlo Avolio, Emanuele D'Amico, Roberto Bergamaschi, Rocco Totaro, Marco Rovaris, Sebastiano Crisafulli, Massimiliano Mirabella, Paola Cavalla, Roberta Fantozzi, Antonio Gallo, Maria Pia Amato, Massimo Filippi, Maria Trojano, Italian Multiple Sclerosis and Related Disorders Registry (I-MS&RD)

Published in

Multiple sclerosis (Houndmills, Basingstoke, England). Pages 13524585261457317. Jul 04, 2026. Epub Jul 04, 2026.

Abstract

In multiple sclerosis (MS), real-world evidence supports early intensive treatment (EIT) with high-efficacy therapies (HET) over escalation (ESC), although comparative data on long-term safety across sequences remain limited.
To compare the incidence of infections and neoplasms in patients treated with different treatment sequences.
Data were extracted from the Italian MS and Related Disorders Register. DMTs were classified as moderate-efficacy treatment (MET), continuous HET (C-HET) or pulsed HET (P-HET). Six therapeutic sequences were reconstructed: MET-only, C-HET-only, P-HET-only, MET→C-HET, MET→P-HET and P-HET→MET. Incidence rates (IRs; per 1000 person-years) and incidence rate ratios (IRRs) were estimated using multivariable Poisson regression, adjusting for age, sex, Expanded Disability Status Scale (EDSS), disease duration, MS phenotype and prior relapse activity.
A total of 37,375 patients were included in the analysis, with a median duration of treatment exposure of 8.8 years. Infection risk was significantly higher with C-HET-only (IR, 24.82; IRR, 3.12), P-HET-only (IR, 13.43; IRR, 1.69), MET→C-HET (IR, 10.46; IRR, 1.32) and MET→P-HET (IR, 12.30; IRR, 1.55) versus MET-only (IR, 7.94), while P-HET→MET showed no significant difference from MET-only (IR, 7.67; IRR, 0.97). Regarding neoplasm incidence, P-HET-only showed the lowest rates (IR, 0.18; IRR, 0.24), whereas it was significantly higher in C-HET-only (IR, 1.33; IRR, 1.79) and MET→C-HET (IR, 1.01; IRR, 1.36) versus MET-only (IR, 0.74).
This is the first real-world study to compare the safety of different sequences in a national registry. ESC strategies did not confer a long-term safety advantage over EIT. Among HET regimens, C-HET was associated with the greatest risk of both serious infections and neoplasms, whereas P-HET showed the lowest neoplasm incidence.

PMID:
42400474
Bibliographic data and abstract were imported from PubMed on 05 Jul 2026.

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