Cladribine Tablets and Relapsing-Remitting Multiple Sclerosis: A Pragmatic, Narrative Review of What Physicians Need to Know

Abstract

Immune reconstitution therapy (IRT) is an emerging management concept for multiple sclerosis, whereby a short course of treatment provides long-lasting suppression of disease activity. "Cladribine tablets 10 mg" refers to a total cumulative dose of cladribine given over 2 years (henceforth referred to as cladribine tablets 3.5 mg/kg); it is a relatively new treatment option that is hypothesised to act as an IRT acting preferentially on the adaptive immune system. A randomised, 2-year, placebo-controlled trial (CLARITY) showed that treatment with cladribine tablets reduced indices of disease activity (relapses, lesions on magnetic resonance images, disability progression) and that this effect outlasted the pharmacologic effect of the treatment on the immune system (mainly a reduction in circulating B and T cells, with little effect on components of the innate immune system such as monocytes). CLARITY Extension, a 2-year extension to this trial, demonstrated durable efficacy, also in patients who received the standard 2-year course of cladribine tablets 3.5 mg/kg and were re-randomised to placebo for a further 2 years. Relative risk reductions for relapse rate with cladribine tablets 3.5 mg/kg were similar for patients with or without prior high disease activity. Reductions in disability progression with cladribine tablets 3.5 mg/kg were higher in patients with prior high relapse rates with or without prior treatment non-response. In this review, we describe the therapeutic profile of cladribine tablets 3.5 mg/kg and provide practical information on initiating this treatment option in the most appropriate patients.

Keywords: Cladribine tablets; Disease-modifying drugs; Immune reconstitution therapy; Relapsing–remitting multiple sclerosis.

Fig. 1

Effects of cladribine tablets 3.5 mg/kg (3.5 mg/kg cumulative dose over 2 years) vs. placebo on outcomes shown in subgroups with higher or lower multiple sclerosis disease activity at baseline in a post hoc analysis from the CLARITY (CLAdRIbine Tablets treating multiple sclerosis orallY) trial. CI Confidence interval, DAT high relapse activity before randomised treatment (see HRA) plus disease activity on treatment, EDSS Expanded Disability Status Scale, Gd⁺ gadolinium-enhancing, HRA high relapse activity before randomised treatment (≥ 2 relapses during the year prior to study entry), MRI magnetic resonance imaging; no evidence of disease activity = no relapses, no 3-month-confirmed EDSS worsening, no T1 Gd⁺ lesions, no active T2 lesions. Adapted from Giovannoni et al. [13], first published by Sage on 2 May 2018, under the terms of the Creative Commons Attribution-NonCommercial 4.0 License