Is therapy-free remission a realistic goal with cladribine tablets in multiple sclerosis? New insights into the mechanism of action and clinical implications of immune reconstitution with cladribine tablets in MS therapy

Oral cladribine is a highly effective pulsed selective immune reconstitution therapy (SIRT) that received approval for the treatment of relapsing multiple sclerosis (RMS) in 2017. The concept of SIRT is characterized by brief exposure to active substances with long-term effectiveness, repopulation of lymphocytes, and maintenance of immune competence. In consequence, cladribine tablets allow patients to enter a prolonged treatment-free period, which offers time windows for family planning and vaccinations. Long-term control of disease activity has been linked to the sustained reduction of memory B cells. Based on more than 17 years of follow-up, the favorable safety profile is characterized by manageable front loading side effects and a low cumulative risk. Overall, therapy with cladribine tablets is associated with a low monitoring burden and leads to high treatment satisfaction. Meanwhile, 15 years after primary results from the pivotal trial were published, a vast amount of new data has emerged, including central effects of cladribine tablets. This narrative review discusses existing and emerging efficacy and safety data for cladribine tablets in MS and links these learnings to different patient profiles encountered in clinical practice. These include young patients with newly diagnosed RMS, young patients with highly active disease, and older patients switching from anti-CD20 antibodies or spingosine-1-phosphate modulators.