Cladribine Tablets for Relapsing-Remitting Multiple Sclerosis: A Clinician's Review

Abstract

Multiple sclerosis (MS) is a chronic neurodegenerative disease characterized by inflammation and demyelination for which there is currently no cure; therefore, the aim of therapy is to reduce the risk of relapse and disability progression. The treatment options for MS have increased greatly in recent years with the development of several disease-modifying therapies (DMTs) and the advent of immune reconstitution therapy (IRT). IRTs are administered in short-dosing periods to produce long-term effects on the immune system. Treatment with an IRT is based on the 3Rs: reduction, repopulation, and reconstitution of lymphocytes, which leads to restoration of immune effector functions. Cladribine tablets represent a selective, high-efficacy, oral form of IRT for patients with MS that targets lymphocytes and spares innate immune cells. Patients require only two weekly treatment courses, with each course comprising two treatment weeks, in Years 1 and 2; therefore, cladribine tablets are associated with a lower monitoring burden than many other DMTs, while short dosing periods can help to improve adherence. This review provides an overview of IRT and offers the clinician's perspective on the current MS treatment landscape, with a focus on practical advice for the management of patients undergoing treatment with cladribine tablets based on the most recent evidence available, including risks associated with COVID-19 and recommendations for vaccination in patients with MS.

Keywords: Cladribine; Disease-modifying therapy; Immune reconstitution therapy; Multiple sclerosis.

Fig. 1

Mode of action of IRT: reduction, repopulation, and reconstitution of lymphocytes—the 3Rs. CMV Cytomegalovirus, HSV herpes simplex virus, IRR infusion-related reaction, IRT immune reconstitution therapy, LLN lower limit of normal, Tregs regulatory T cells, VZV varicella-zoster virus

Fig. 2

a Treatment and monitoring burden of cladribine tablets. b Yearly treatment burden for cladribine tablets and other DMTs. ^aTotal number of administrations over the first 12 months of treatment. ^b10 mg tablets given as a cumulative dose of 3.5 mg/kg over 2 years, administered as 1 treatment course of 1.75 mg/kg per year for 2 years. DMTs Disease-modifying therapies, IFNβ interferon-beta, MRI magnetic resonance imaging, sc subcutaneous

Fig. 3

Treat-2-target algorithm of NEDA in relapsing forms of MS (adapted from Giovannoni et al. [39]). MS Multiple sclerosis, NABs neutralizing antibodies, NEDA no evidence of disease reactivation, Rx treatment

Fig. 4

Yearly monitoring burden for cladribine tablets and other DMTs [, , , –148]. CV Cardiovascular, DMTs disease-modifying therapies, HBV hepatitis B virus, HCV hepatitis C virus, MRI magnetic resonance imaging, TB tuberculosis

Fig. 5

Incidence of herpes zoster per 1000 patient years, across different multiple sclerosis treatments [107, 149, 150]. BID Twice daily, MS multiple sclerosis