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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 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.

Background The treatment effects in multiple sclerosis (MS) clinical trials are often estimated by monitoring disease activity by the count of “active” plaques on T2-weighted or gadolinium (Gd)-enhanced T1-weighted magnetic resonance imaging (MRI). Objective To evaluate the relationship between the treatment effects estimated on T2-weighted or Gd-enhanced T1-weighted MRI. Methods Data were extracted from published randomized clinical trials in relapsing-remitting MS with frequent MRI, reporting both active T2 and Gd-enhancing lesions. A regression analysis was performed between the treatment effects estimated on the two different MRI endpoints. Results A strong association was found between the treatment effect on Gd-enhancing lesions and on active T2 lesions (R2 = 0.93), and the treatment effect estimates were almost the same (slope = 0.96). Conclusion Defining either active T2 or Gd-enhancing lesions as MRI endpoint seems to be not crucial for monitoring MRI activity in MS clinical trials. The choice of the best MRI endpoint should be based on different considerations (e.g., sensitivity, reproducibility, time for assessment, safety, and patients’ comfort). Further monitoring active T2 lesions could allow less expensive trials, without requiring injection of Gd-based contrast agents.

This study aimed at evaluating the influence of a different slice orientation on brain magnetic resonance imaging (MRI) lesion load in multiple sclerosis (MS). Fifteen MS patients were scanned obtaining both axial and sagittal conventional spin echo (24 slices; TR 2400, TE 30/80) brain MRI. The total lesion load (TLL) was assessed twice for each scan, using a semi-automated local thresholding technique and the same marked hardcopies. The mean TLL was 22734 mm3 for axial and 22003 mm3 for sagittal scans. The mean intra-observer coefficient of variation (COV) was 4.65% for the axial acquisitions and 4.52% for the sagittal acquisitions. This difference was not statistically significant (one-way ANOVA, P> 0.1). The lesion load was significantly higher from axial MRI as compared to the intra-observer variability (two-way ANOVA, P =0.01), but the fluctuations around this average difference between axial and sagittal scan TLL were significantly large (test for interaction, P < 0.00I). Our data indicate that the use of sagittal conventional MRI scans does not seem to be worthwhile for the quantitative assessment of lesion load in MS patients.