Treatment-free remission in MS: long-term disease control with cladribine tablets

Oral cladribine, a highly effective pulsed selective immune reconstitution therapy (SIRT) for relapsing multiple sclerosis (RMS) is characterised by extended treatment-free periods following brief exposure to medication. Since approval in 2017, long-term real-world data have become available which provide insight into the management of patients treated with cladribine tablets beyond year 4. Most patients remained without additional therapy, which may hint at stable disease control. However, the absence of further treatment must not necessarily be interpreted as absence of any disease activity, as MRI data are often incomplete in watch-and-wait cohorts. The observed long-term remission is likely linked to the unique mode of action, which involves rapid repopulation of lymphocytes with different dynamics amongst subsets and sustained reduction of memory B cells. The recovery of the immune system and lymphocytes preserves long-term therapeutic options with existing or upcoming drugs. In cases of mild recurring disease activity, retreatment with cladribine tablets has been shown to be effective and tolerable within the known safety profile. Unrestricted long-term management options associated with cladribine tablets include a switch to other DMTs in cases of insufficient disease control. Overall, cladribine tablets show potential of a paradigmatic shift in MS management that may enable treatment-free remission over 6 years as an achievable treatment goal in a substantial proportion of RMS patients.