French expert opinion on the long-term management of relapsing multiple sclerosis with cladribine tablets beyond year 4.

Cladribine tablets (CladT) is a high-efficacy treatment (HET) for the management of relapsing multiple sclerosis (RMS) that acts as an immune reconstitution therapy (IRT). Administered as two short annual courses, CladT has been shown to provide durable disease control in responders for up to 11 years, extending well beyond the short treatment periods. Randomised trials do not offer evidence-based guidance on the therapeutic use of CladT beyond four years post-initiation, leading to variability in long-term management strategies in real-world practice, notably with respect to the possibility of additional treatment. We propose a pragmatic algorithm for long-term treatment with CladT, grounded in currently available data and our French collective clinical experience, intended to assist neurologists in therapeutic decision-making in year 5 and beyond. We suggest a practical classification of patients into two main profiles after the initial 4-year period: those who remain clinically and radiologically stable, and those who exhibit evidence of disease reactivation. A stable profile, which encompasses a large proportion of treated patients, may be managed through continued monitoring or additional treatment, depending on individual presentations and the presence or absence of factors associated with higher likelihood of RMS reactivation before CladT initiation. For patients demonstrating signs of disease activity, options include additional treatment with CladT or transitioning to another HET, according to the severity of inflammatory reactivation.