Role of Immune Reconstitution Therapy with Cladribine Tablets in the Management of Relapsing Multiple Sclerosis in Older Patients

Neurol Ther. 2025 May 17. doi: 10.1007/s40120-025-00767-1. Online ahead of print.

ABSTRACT

The pathophysiology and presentation of relapsing multiple sclerosis (RMS) differ importantly between younger and older patients. Older patients usually suffer fewer MS relapses but present with a chronically inflammatory phenotype (inflammaging) associated with accelerated age-related changes to the adaptive and innate immune systems (immunosenescence). The efficacy of most disease-modifying therapies (DMTs) appears to decline with increasing age, likely because of a shift away from focal inflammation as the main driving force for progression of MS. These observations led to suggestions that DMT may be withdrawn for an older person with very stable MS. However, this approach risks the resumption of MS disease activity. In contrast, analyses of evaluations of immune reconstitution therapy with cladribine tablets (CladT) show that this high-efficacy DMT appears to be effective and well tolerated irrespective of age. Achieving long-term freedom from MS disease activity for an older patient with MS is feasible using this approach. Switching to CladT is a rational option for reducing the dual burdens of continuous treatment (including side effects associated with continuous immunosuppression with some DMTs) and monitoring for older people with RMS. This includes possible use as an “exit therapy”, beyond which some patients may not need pharmacological therapy for their RMS in the future.

PMID:40381137 | DOI:10.1007/s40120-025-00767-1