Real-World Data for Safety Studies: Challenges and Opportunities From the Italian Multiple Sclerosis and Related Disorders Register

Introduction: Information on the safety profile of disease-modifying therapies (DMTs) in multiple sclerosis (MS) is often lacking in routine clinical practice. Real-world data sources, such as patient registries, support pharmacovigilance to characterise safety signals, as recently recognised by regulatory agencies. In Italy, the "Italian Multiple Sclerosis and Related Disorders Register" (RISM) was officially launched in 2015 to collect demographic and clinical data from patients with MS. Purpose: To describe the main characteristics of RISM as a research platform supporting the safety evaluation of MS therapies. Methods: RISM enables the systematic characterisation of clinical events occurring in treated patients and, over the years, has implemented procedures to ensure high-quality data collection. A study cohort including subjects who initiated a DMT between 2016 and 2025 is analysed using descriptive statistics. Clinical events recorded during the study period are reported as absolute numbers and frequencies. Results: Between 2016 and 2025, a total of 24 259 subjects received at least one DMT, and 4419 of them (18.2%) experienced one or multiple clinical events. For descriptive purposes, the occurrence of infections and malignancies, which accounted for 29.4% and 3.7% of all the clinical events collected in RISM respectively, are reported and categorised. Conclusions: This article outlines the strengths and limitations of RISM in conducting safety studies and highlights the methodological and legal challenges associated with such platforms. Routinely collected healthcare data within RISM provide a comprehensive, patient-centred perspective for the long-term evaluation of DMT safety and can address relevant questions on drug policies and public health.