Cladribine 10 mg tablets (Mavenclad®, now referred to as cladribine) is a pulsed, second-line immune reconstitution therapy licensed by the European Medicines Agency (EMA) in 2017 for the treatment of active relapsing MS (RMS). A cumulative dosage of 3.5 mg/kg body weight over 2 years, administered during week 1 and week 5 each year, has been determined effective and safe in the pivotal CLARITY and CLARITY Extension trials (EMA, 2022b; Giovannoni et al., 2010, 2018). Treatment with cladribine, a synthetic deoxyadenosine analog, sequels a rapid depletion of lymphocytes, followed by reconstitution of the adaptive immune system (Comi et al., 2019). The selectiveness of cladribine towards memory T and B cells and the relative expansion of regulatory T cells within the T-cell population allows the homeostatic immunological environment to restore and suppress autoreactive lymphocytes (Moser et al., 2020; Stuve et al., 2019). Thus, a short intermittent treatment course with cladribine induces a durable efficacy beyond the treatment period. During the CLARITY Extension trial, a cladribine treatment course of 2 years produced clinical benefits comparable to a 4-year treatment course (Giovannoni et al., 2018). The therapeutic benefits even remained for up to 6 years after the treatment start (Giovannoni et al., 2021).

The available knowledge on cladribine for MS is mainly derived from randomized controlled trials (RCTs) or long-term evaluations of the RCT population (Giovannoni et al., 2021; Leist et al., 2014; Montalban et al., 2018; Patti et al., 2020). However, these results may not be generalizable to a diversified population of people with MS (pwMS), as an RCT design is highly restricted to limit bias and confounding (Blonde et al., 2018). The pivotal RCTs excluded, among others, pwMS having comorbidities, who received ≥2 prior disease-modifying therapies (DMTs), with an Expanded Disability Status Scale (EDSS) >5.5, and the elderly (>65 years) (Giovannoni et al., 2010). Since the market authorization of cladribine for MS in Europe, real-world experience has been gathered, and observational data is currently emerging (Bose et al., 2021; Lizak et al., 2021; Möhn et al., 2019; Petracca et al., 2022; Pfeuffer et al., 2022; Rauma et al., 2022; Rolfes et al., 2021; Sorensen et al., 2023). Such reports provide crucial information on the performance of cladribine treatment in pwMS in regions and settings, which complement the RCT findings (Blonde et al., 2018).

This report describes the real-world clinical outcomes of pwMS treated with cladribine at our Belgian institute. Hereby, we focus on effectiveness in terms of 'no evidence of disease activity' (NEDA-3), following distinct previous exposures to DMTs, and the safety of cladribine treatment.