Short-term combination of glatiramer acetate with IV steroid treatment preceding treatment with GA alone assessed by MRI-disease activity in patients with relapsing–remitting multiple sclerosis Nicola De Stefano a, ⁎ , Massimo Filippi b , Clive Hawkins c (and the 9011 study group) a Department of Neurological and Behavioral Sciences, University of Siena, Italy b Neuroimaging Research Unit, Department of Neurology, Scientific Institute and University Ospedale San Raffaele, Milan, Italy c Keele University Medical School/University Hospital of North Staffordshire, Stoke-on-Trent, UK Received 12 June 2007; received in revised form 22 August 2007; accepted 27 August 2007 Available online 25 September 2007 Abstract Objectives: To assess if short-term combination of glatiramer acetate (GA) and IV steroid in patients with relapsing–remitting multiple sclerosis (RRMS) is safe and sustains the effect of GA treatment on MRI-disease activity. Methods: RRMS patients with ≥ 2 gadolinium (Gd)-enhancing lesions on screening MRI and EDSS score ≤ 4.0 received GA injection (20 mg subcutaneously once daily) and monthly 1 g IV Methylprednisolone (IVMP) for 6 months. Afterwards, all subjects received GA injections daily alone for additional 6 months. Neurological evaluations were performed at screening, baseline and every 3 months. Laboratory tests for safety were performed at screening, baseline, months 1, 6 and 12. Brain MRIs were performed at screening, baseline, months 5, 6, 11, and 12 to assess the change in the number of Gd-enhancing lesions i) from baseline to month 6, and ii) from baseline to month 12 compared with the change from baseline to month 6. Results: 89 subjects were eligible for the study. In this group, GA in combination with IVMP resulted in 65% (95% CI=0.25–0.49, p b 0.0001) reduction in the number of Gd-enhancing lesions. This reduction was sustained for additional 6 months when patients received GA alone. The analysis for change achieved in the second 6 month period showed no difference from the change achieved in the first six months (ratio 0.75, 90% CI = 0.468–1.197). Overall, treatment was well tolerated and adverse events reported were similar to the known safety profile of GA. Conclusions: Short-term combination of GA with 1 g monthly IVMP, preceding treatment with GA alone, is safe. MRI data suggest that this combination therapy may result in an early and sustained reduction of disease activity in RRMS patients. © 2007 Elsevier B.V. All rights reserved. Keywords: Multiple sclerosis; MRI; Glatiramer acetate; Methylprednisolone 1. Introduction All current available disease-modifying treatments (DMT) for relapsing–remitting multiple sclerosis (RRMS) are only partially effective on clinical measures of disease activity and evolution [1]. Three pivotal trials [2–5] and a meta-analysis of those studies [6] support the benefit of glatiramer acetate (Copaxone®, GA) 20 mg by daily subcutaneous injections on relapse rate and magnetic resonance imaging (MRI) lesion activity in RRMS patients. A trend toward a potential effect on accumulation of disability has also been shown [6]. In addition, a long-term open-label study also demonstrated the safety and tolerability of GA [7]. Journal of the Neurological Sciences 266 (2008) 44 – 50 www.elsevier.com/locate/jns ⁎ Corresponding author. Department of Neurological and Behavioral Sciences, Viale Bracci 2, 53100, Siena, Italy. Tel.: +39 0577 233432; fax: +39 0577 233411. E-mail address: destefano@unisi.it (N. De Stefano). 0022-510X/$ - see front matter © 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.jns.2007.08.036