The effect of daclizumab on brain atrophy in relapsing-remitting multiple sclerosis

Abstract

Daclizumab is a monoclonal antibody that reduces inflammation in multiple sclerosis (MS). Through a retrospective analysis, our objective was to determine whether daclizumab treatment reduces the rate of brain structure atrophy in comparison to a mixture of other disease-modifying therapies (mainly different interferon β preparations). We analyzed MRI examinations (1332 scans from 70 MS cases) obtained between 2000 and 2011 in a single center and processed with an automated brain segmentation method. We used mixed-effects multivariable linear regression models to determine whether a median of 4.3 years of daclizumab therapy in 26 patients altered rates of brain-volume change, controlling for variations in MRI protocol. The control group consisted of 44 patients not treated with daclizumab. We found that supratentorial brain volume declined by 5.17 ml per year (95% confidence limits: 3.58-6.77) off daclizumab therapy. On daclizumab, the annual rate of volume loss decreased to 3.72 ml (p=0.01). The rate of ventricular enlargement decreased from 1.26 to 0.42 ml per year (p<0.001). Focused analysis suggests that reduction in gray matter atrophy rate most likely underlies these results. In summary, in this retrospective analysis, daclizumab therapy substantially decreased the rate of brain atrophy in relapsing-remitting MS in comparison to other disease-modifying therapies, predominantly interferon β.

Keywords: Brain atrophy; Brain volume; Daclizumab; Gray matter; Interferon beta; Multiple sclerosis.

Fig. 1

Distribution of non-daclizumab disease-modifying therapies: IFN, interferon; SC, subcutaneous; IM, intramuscular.

Fig. 2

Schematic depiction of the segmentation process, which uses T2-FLAIR and T1-weighted images to derive tissue segmentation including lesions (red), cerebral white matter (white), cerebral cortex (dark orange), caudate (light orange), putamen (light yellow), thalamus (dark yellow), and ventricles (brown). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

Fig. 3

Supratentorial brain volume (A, small points) and ventricular volume (B, small points), with corresponding model fits (solid lines), for each participant. In both, a change in slope can be seen in the daclizumab cases (red points and lines), beginning 90 days after initiation of therapy and ending 90 days after cessation. Data points are corrected for differences relating to acquisition protocols, as described in Section 2.