Potential mechanisms of action related to the efficacy and safety of cladribine

Publication date: Available online 14 February 2019Source: Multiple Sclerosis and Related DisordersAuthor(s): David Baker, Gareth Pryce, Samuel S. Herrod, Klaus SchmiererAbstractOral cladribine is a novel treatment for relapsing multiple sclerosis (MS). This is a semi-selective immune-reconstitution therapy that induces long-term therapy from short treatment cycles. It has a relatively good safety profile that currently does not require extensive monitoring associated with some continuous immunosuppressive and relatively non-selective immune reconstitution therapies. The efficacy and safety of cladribine relates to its particular physicochemical properties, the function of the lymphocyte subsets that are selectively targeted by the drug and the repopulation kinetics of these subsets. As such, there is marked and long-term depletion of memory B cell subsets, which probably relates to the therapeutic efficacy. This is also coupled with a more limited, but likewise long-term, depletion of CD4 T subsets. There is limited depletion of cells of the innate immune system and modest effects on CD8 and probably plasma cells, which provide immediate and durable protection from infection. Targeting of CD4 T regulatory cells, CD8 T suppressor cells and regulatory B cell subsets appears more limited as these populations recover rapidly and so repopulating pathogenic cells re-emerge into a regulatory environment. This appears to lead to re-establishment of immune-tolerance that produces lon...

Source: Multiple Sclerosis and Related Disorders - February 14, 2019 Category: Neurology Source Type: research