How does oral cladribine change immune cells in relapsing multiple sclerosis?

Oral cladribine is a disease-modifying therapy for relapsing multiple sclerosis (MS). It works by temporarily reducing specific immune cells that drive inflammation. Research shows cladribine affects immune cells both in the blood and in the central nervous system (CNS), including the fluid around the brain and spinal cord (cerebrospinal fluid, or CSF). It also changes the behavior of microglia, the immune cells that reside in the brain. These changes help calm the immune attack on the nervous system.

What the research says

Cladribine is a prodrug that selectively depletes lymphocytes, a type of white blood cell ¹⁰. A 2020 laboratory study found that cladribine modifies the function of microglia, the brain's resident immune cells. When microglia were activated (as they are in MS), cladribine reduced their granularity, phagocytic ability, and random migration—all signs of dampened activity. This effect was seen at concentrations that likely occur in human CSF, suggesting cladribine acts directly in the CNS ¹⁰.

A 2026 study examined immune cells in the CSF of people with relapsing MS treated with cladribine tablets. Using single-cell sequencing, researchers found that cladribine profoundly changed the types of immune cells present in the CSF. Specifically, it reduced switched memory B cells (a type of B cell linked to MS attacks) while allowing naive B cells (immature B cells) to recover. Similar changes were seen in the blood. The study also noted a reduction in CD4+ T cells in the CSF, but the overall transcriptional phenotype of remaining cells was not altered ¹¹.

Another 2026 study from the CLARIFY-MS trial looked at cognitive function and employment in people with relapsing MS treated with cladribine tablets over two years. Cognitive test scores (BICAMS battery) remained stable, and most participants had stable or improved processing speed (measured by SDMT). Brain volume loss was low, and employment status did not worsen—over 40% of participants remained employed ⁹. These findings suggest that cladribine's immune effects help preserve brain function and daily life.

Together, these studies show that cladribine reduces harmful immune cells in both blood and CSF, calms microglia, and allows the immune system to rebalance. This helps control MS relapses and may protect against long-term disability.

What to ask your doctor

• How does cladribine compare with other MS treatments in terms of its effects on immune cells?
• Are there any specific monitoring tests (like blood counts or CSF analysis) recommended during cladribine treatment?
• Could cladribine's effects on microglia offer additional benefits for my MS symptoms?
• What should I know about the timing of immune cell recovery after cladribine treatment?
• How might cladribine affect my risk of infections or other immune-related side effects?