Evaluating the effectiveness of simvastatin in slowing the progression of disability in secondary progressive multiple sclerosis: a synopsis of MS-STAT2, a multicentre, randomised controlled, double-blind, phase 3 clinical trial

Williams T, Blackstone J, John N, Braisher M, De Angelis F, Bianchi A, Calvi A, Doshi A, Mangion SA, Wade C, Bordea E, Merry R, Garton G, Lyle D, Jarman E, Mahad D, Shehu A, Arun T, McDonnell G, Geraldes R, Craner M, Hillier C, Ganesalingam J, Fisniku L, Hobart J, Spilker C, Robertson NP, Kalra S, Pluchino S, Harikrishnan S, Mattoscio M, Harrower T, Young C, Lee M, Kumar Chhetri S, Ahmed F, Rog D, Silber E, Gallagher P, Duddy M, Straukiene A, Nicholas R, Rice C, Tebbs S, Hawton A, Hunter R, Giovannoni G, Ciccarelli O, Beveridge J, Nixon S, Thompson AJ, Greenwood J, Pearson O, Evangelou N, Sharrack B, Galea I, Pavitt S, Chandran S, Ford HL, Nicholas JM, Chataway J
Record ID 32018015741
English
Authors' objectives: Despite the relative success of immuno-modulatory disease-modifying therapy in relapsing remitting multiple sclerosis, progressive worsening of disability remains a major problem, particularly for those with secondary progressive multiple sclerosis. Various underlying mechanisms are likely to contribute, augmented by comorbidities (such as vascular risk) and ageing. In the phase 2b MS-STAT trial, simvastatin (80 mg) (Sandoz Ltd, Camberley, UK) reduced the mean annualised whole brain atrophy rate by 43% compared to placebo in patients with secondary progressive multiple sclerosis (p = 0.003). We now report the phase 3, MS-STAT2 trial, with confirmed progression of disability as the primary outcome.
Authors' methods: A multicentre, phase 3, randomised, double-blind, placebo-controlled clinical trial was conducted at 31 UK neuroscience centres and district general hospitals. Secondary progressive multiple sclerosis participants aged 18–65 years were randomised 1 : 1 to oral simvastatin (80 mg), or matched placebo, based on a minimisation algorithm that incorporated the following factors: sex (male/female); age (< or ≥ 45 years); Expanded Disability Status Scale baseline score (≤ 5.5 or ≥ 6); whether participants were taking newly licensed (2017 onward) disease-modifying treatments for secondary progressive multiple sclerosis; and trial site. An independent and secure online randomisation service was used. All participants, site investigators and the trial co-ordinating team were blinded to treatment allocation. The Expanded Disability Status Scale was measured every 6 months and was compared to baseline scores, with remote data collection used when enforced by the COVID-19 pandemic. The primary outcome was time to Expanded Disability Status Scale-confirmed disability progression. Progression of disability was defined as an increase of at least one point on the Expanded Disability Status Scale if the baseline score was
Details
Project Status: Completed
URL for project: https://www.journalslibrary.nihr.ac.uk/programmes/hta/15/57/143
Year Published: 2026
URL for published report: https://www.journalslibrary.nihr.ac.uk/hta/GJJC5820
URL for additional information: English
English language abstract: An English language summary is available
Publication Type: Full HTA
Country: England, United Kingdom
DOI: 10.3310/GJJC5820
MeSH Terms
  • Multiple Sclerosis
  • Multiple Sclerosis, Chronic Progressive
  • Simvastatin
  • Disease Progression
Contact
Organisation Name: NIHR Health Technology Assessment programme
Contact Address: NIHR Journals Library, National Institute for Health and Care Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK
Contact Name: journals.library@nihr.ac.uk
Contact Email: journals.library@nihr.ac.uk
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