Reduced brain atrophy rates are associated with lower risk of disability progression in patients with relapsing multiple sclerosis treated with cladribine tablets

Nicola De Stefano, Antonio Giorgio, Marco Battaglini, Alessandro De Leucio, Christine Hicking, Fernando Dangond, Gavin Giovannoni, Maria Pia Sormani, Nicola De Stefano, Antonio Giorgio, Marco Battaglini, Alessandro De Leucio, Christine Hicking, Fernando Dangond, Gavin Giovannoni, Maria Pia Sormani

Abstract

Background: Neuroimaging studies have used magnetic resonance imaging-derived methods to assess brain volume loss in multiple sclerosis (MS) as a reliable measure of diffuse tissue damage.

Methods: In the CLARITY study ( ClinicalTrials.gov NCT00213135), the effect of 2 years' treatment with cladribine tablets on annualized percentage brain volume change (PBVC/y) was evaluated in patients with relapsing MS (RMS).

Results: Compared with placebo (-0.70% ± 0.79), PBVC/y was reduced in patients treated with cladribine tablets 3.5 mg/kg (-0.56% ± 0.68, p = 0.010) and 5.25 mg/kg (-0.57% ± 0.72, p = 0.019). After adjusting for treatment group, PBVC/y showed a significant correlation with the cumulative probability of disability progression (HR = 0.67, 95% CI = 0.571, 0.787; p < 0.001), with patients with lower PBVC/y showing the highest probability of remaining free from disability progression at 2 years and vice versa.

Conclusions: Cladribine tablets given annually for 2 years in short-duration courses in patients with RMS in the CLARITY study significantly reduced brain atrophy in comparison with placebo treatment, with residual rates in treated patients being close to the physiological rates.

Keywords: Brain atrophy; CLARITY; brain volume; cladribine; disease progression; relapsing multiple sclerosis.

Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: N.D.S. has received honoraria from Schering, Biogen Idec, Teva Pharmaceutical Industries Ltd, Novartis, Genzyme Corporation, Roche, and Merck for consulting services, speaking, and travel support. He serves on advisory boards for Biogen Idec, Merck, Novartis, Genzyme Corporation, and Roche. He has received research grant support from the Italian MS Society. A.G. has no conflicts of interest to declare. M.B. has no conflicts of interest to declare. A.D.L. has no conflicts of interest to declare. C.H. is an employee of Merck KGaA, Darmstadt, Germany. F.D. is an employee of EMD Serono, Inc, Billerica, MA, USA, a business of Merck KGaA, Darmstadt, Germany. G.G. serves on advisory boards for Merck, Biogen Idec, and Vertex Pharmaceuticals; has received speaker honoraria and consulting fees from Bayer Schering Pharma, FivePrime, GlaxoSmithKline, GW Pharmaceuticals, Merck, Biogen Idec, Pfizer Inc, Protein Discovery Laboratories, Teva Pharmaceutical Industries Ltd, Sanofi-Aventis, UCB, Vertex Pharmaceuticals, Genzyme Corporation, Ironwood, and Novartis; serves on the Merck speakers bureau; and received research support unrelated to this study from Biogen Idec, Merck, Novartis, and Ironwood. M.P.S. has received personal compensation for consulting services and for speaking activities from Genzyme Corporation, Merck, Teva Pharmaceutical Industries Ltd, Synthon, Actelion, Novartis, and Biogen Idec.

Figures

Figure 1.
Figure 1.
Effect of treatment on (a) mean PBVC for months 0–6, (b) mean PBVC for months 6–24, and (c) rate of disability-progression-free survival in PBVC/year tertiles in the CLARITY study.

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Source: PubMed

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