Cladribine Tablets Improve MRI Outcomes in Patients With Highly Active Relapsing-Remitting MS

NASHVILLE—Treatment with cladribine tablets 3.5 mg/kg reduces MRI markers of disease activity in patients with highly active relapsing-remitting multiple sclerosis (MS), according to research described at the 2018 CMSC Annual Meeting. Results of a post hoc analysis of the CLARITY study indicated that in patients with relapsing MS who were selected for further study based on high disease activity, treatment with cladribine tablets 3.5 mg/kg showed efficacy in reducing MRI markers of disease activity comparable with the overall CLARITY study population.

In the CLARITY study, treatment with cladribine tablets versus placebo showed strong efficacy in a large cohort of patients with relapsing MS over two years. Because patients with high disease activity have a high risk of relapses and disability, Gavin Giovannoni, MBBCh, PhD, and his CLARITY collaborators conducted a post hoc analysis to compare the effects of cladribine tablets 3.5 mg/kg versus placebo on outcomes assessed by MRI in subgroups of CLARITY patients with evidence of high disease activity at study entry. Professor Giovannoni is Chair of Neurology at the Blizard Institute of Cell and Molecular Science, Barts and the London School of Medicine and Dentistry at Queen Mary University of London.

Gavin Giovannoni, MBBCh,PhD

The researchers retrospectively analyzed CLARITY participants randomized to cladribine tablets 3.5 mg/kg or placebo using the following two sets of high disease activity criteria based on relapse history, prior treatment, and MRI characteristics: 1) high relapse activity, which was defined as two or more relapses during the year before study entry whether on disease-modifying therapy or not; 2) high relapse activity plus treatment nonresponse, in which treatment nonresponse was defined as one or more relapses and one or more T1 gadolinium-enhancing lesions or nine or more T2 lesions during the year before study entry and while on therapy with other disease-modifying therapy.

For cumulative new T1 gadolinium-enhancing lesions, the relative risk ratio in the high relapse activity subgroup (0.087) was significantly lower in favor of cladribine tablets 3.5 mg/kg (n = 130) over placebo (n = 131). In the high relapse activity plus treatment nonresponse subgroup, the relative risk ratio (0.077) also significantly favored cladribine tablets 3.5 mg/kg (n = 140) versus placebo (n = 149). The risk reductions (91% and 92%, respectively) were similar to the 90% reduction in the overall CLARITY population (0.097), said the researchers.

For cumulative active T2 lesions, the relative risk ratio also significantly favored cladribine tablets 3.5 mg/kg versus placebo for the high relapse activity (0.263) and the high relapse activity plus treatment nonresponse subgroups (0.254), with risk reductions of 74% and 75%, reflecting the 73% reduction in the overall population (0.272).

The relative risk ratio for cumulative combined unique active lesions significantly favored cladribine tablets 3.5 mg/kg versus placebo for high relapse activity (0.212) and high relapse activity plus treatment nonresponse (0.203) with risk reductions of 79% and 80%, reflecting the 77% overall population reduction (0.234). Comparable results were observed in the non-high-disease activity counterparts, with no significant treatment-subgroup interactions.

—Erica Tricarico

Suggested Reading

Giovannoni G, Soelberg Sorensen P, Cook S, et al. Efficacy of cladribine tablets in high disease activity subgroups of patients with relapsing multiple sclerosis: A post hoc analysis of the CLARITY Study. Mult Scler. 2018 April 1 [Epub ahead of print].