Multiple sclerosis (MS) is recognised as a chronic immune-mediated inflammatory, neurodegenerative and demyelinating disease of the central nervous system. Important progress has been registered to better understand its epidemiology, and also the availability of new therapeutic tools allowed a better management of disease course. Over the last few years the therapeutic landscape for MS has evolved greatly with the introduction of new therapies, whose balance between efficacy, safety, and management has been increasingly favorable (Cree et al., 2019; Yang et al., 2022; Gholamzad et al., 2019).

Disease registers, also called patient registers, have been recognised as a powerful tool (EMA 2021; Gliklich et al., 2020) to assess the profile of different therapies recorded over the years, thus enabling a better evaluation of long-term exposure, the incidence of (rare) adverse events, or the consequences of combinations of multiple treatments (Trojano et al., 2017; Dobson et al., 2022). In recent years, several MS disease registers have been established in Europe (Glaser et al., 2019), providing the opportunity to conduct real-world observational studies in large cohorts of persons with multiple sclerosis (pwMS).

The dynamic therapeutic setting has led to a change in prescribing behaviors in MS expert centers (M Filippi et al., 2022; Harding et al., 2019; Seifer et al., 2023). This is obviously related to a period factor, but also by other aspects such as the center's location and patients’ characteristics. While the influence of the time patterns of therapeutic availability is well known and documented in various countries (Marangi et al., 2020; Earla et al., 2020; Leblanc et al., 2021; Ghadiri et al., 2022), evidence on the relationships with other factors is scanty. Many disease-modifying therapies (DMT) have been introduced for the treatment of MS in the last two decades. A great consensus among scientific evidence confirms the need to increase early treatment with high-efficacy (HE) DMT for the majority of MS patients. How national regulatory authority approval of these new treatments changed prescribing behaviors in current clinical practice is now being evaluated in several countries (Henderson et al., 2023; Spelman et al., 2021 Oct 1). Our previous study (Bergamaschi et al., 2022) demonstrated some heterogeneities in the first MS phenotype recorded in clinical center. This is partially explainable by differences in centers’ characteristics and partially by the geographic residence of patients. Given these premises, the objective of this study is to assess, through real-world data, the changes in prescription patterns between moderate-efficacy (ME) and HE-DMT, in different time periods and in five geographic areas in Italy. Indeed, the IMS&RD Register (Trojano et al., 2019; Mosconi et al., 2023) covers a large number of patients in all Italian regions, who are recruited and followed along an extensive period of time. This setting offers an invaluable opportunity to study spatial and temporal variations in current prescribing practice.