High-dose simvastatin does not slow disability progression in SPMS

The highly anticipated primary results of the phase 3 MS-STAT2 trial failed to show that high-dose simvastatin slows disability progression in secondary progressive MS (SPMS). Simvastatin treatment was safe and well tolerated.

Previously, the phase 2b MS-STAT trial (NCT00647348) demonstrated a reduction of 43% in the mean rate of whole brain atrophy over 2 years in patients with SPMS, with simvastatin at a dose of 80 mg/day [1]. Stimulated by those outcomes, Dr Jeremy Chataway (University College London, UK) and colleagues designed the randomised-controlled MS-STAT2 trial (NCT03387670) [2].

MS-STAT2 was conducted at 31 hospital sites in the UK. Participants had SPMS with steady progression rather than relapse as the major cause of increasing disability in the preceding 2 years. They had to be 25 to 65 years of age and have an Expanded Disability Status Scale (EDSS) score of 4.0 to 6.5. The participants were randomised to simvastatin 80 mg (40 mg in the first month) or matching placebo for up to 4.5 years. The primary outcome was confirmed disability progression (CDP).

The mean age of the 964 participants was 54 years, 73% were women, and the mean MS duration was 23 years. Only 5% had had relapse activity in the previous year. Compliance was over 80%. “There was no effect of simvastatin on the progression rate in this population of patients with progressing MS,” Prof. Chataway said. “The cumulative incidence of progression was around 40%.” The hazard ratio versus placebo was 1.13 (95% CI 0.91–1.31; P=0.26). A total of 365 progression events were confirmed.

Since the study was conducted during the COVID-19 crisis, the researchers did a sensitivity analysis to detect possible differences in treatment effect during 3 distinct periods (before, during, and after COVID-19-related restrictions). No evidence for a difference was found in treatment effect or relapse rate. However, there was a markedly confirmed increase in progression events during COVID-19 restrictions, which might be explained by, for example, deconditioning or loss of access to physiotherapy.

Prof. Chataway added that the safety data was generally “excellent.” He announced that many more (secondary) outcomes will be reported in the months to come, including analyses of patient-reported outcomes, biofluid markers, and MRI.

1. Chataway J, et al. Lancet. 2014;383(9936):2213-21.
2. Chataway J, et al. Evaluating the effectiveness of simvastatin in slowing the progression of disability in secondary progressive multiple sclerosis (MS-STAT2 trial): a multicentre, randomised, placebo-controlled, double-blind phase 3 clinical trial. Abstract O134, ECTRIMS 2024, 18–20 September, Copenhagen, Denmark.

 

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Posted on 18 November 202418 November 2024