Simvastatin fails as disease-modifying treatment for Parkinson's disease patients: JAMA
UK: Findings from a recent randomized clinical trial published in JAMA Neurology have shown simvastatin to be ineffective as a disease-modifying therapy in patients with Parkinson's disease (PD) of moderate severity.
Parkinson's disease is the fastest-growing neurological condition globally, affecting more than 6.2 million people. Current treatments manage symptoms of Parkinson's disease, but no known treatment slows disease progression. Preclinical and epidemiological studies support statins' potential use as disease-modifying therapy.
Considering the above, Kara N. Stevens, Faculty of Health, University of Plymouth, Plymouth, United Kingdom, and colleagues aimed to determine whether simvastatin has the potential as a disease-modifying treatment for moderate PD patients.
For this purpose, the researchers conducted a randomized clinical trial, a double-blind, parallel-group, placebo-controlled futility trial between March 2016 and May 2020, within 23 National Health Service Trusts in England. The trial included participants aged 40 to 90 years with an idiopathic PD diagnosis. They had a modified Hoehn and Yahr stage of 3.0 or less while taking medication and were taking dopaminergic medication with a wearing-off phenomenon. Data analysis was performed with additional research in February 2021.
Participants were allocated 1:1 to receive simvastatin or matched placebo, stratified by site and Hoehn and Yahr stage. In the simvastatin group, the patients entered a 1-month phase of simvastatin, 40 mg daily, followed by 23 months of simvastatin, 80 mg daily, before a 2-month washout.
A 24-month change in the Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UPDRS) part III score (prespecified primary outcome) was measured while not taking medication (a high score implies worse results). The participants who commenced the 80-mg phase and had valid primary outcome data were included in the preliminary futility analysis. All participants who began trial treatment were included in the safety analysis and reported by dose at the time of the event.
The study led to the following findings:
- Of 332 patients assessed for eligibility, 32 declined, and 65 were ineligible. Of 235 recruited participants, 41% were female, 99% were White, and the mean age was 65.4 years. A total of 216 patients progressed to the 80-mg dose.
- Primary outcome analysis (n = 178) indicated the simvastatin group had an additional deterioration in MDS-UPDRS III score while not taking medication at 24 months versus the placebo group (1.52 points).
- A total of 37 serious adverse events (AEs), including three deaths, and 171 AEs were reported for participants receiving 0 mg of simvastatin; 37 serious AEs and 150 AEs were reported for participants taking 40 mg or 80 mg of simvastatin.
- Four participants withdrew from the trial because of an AE.
"Our findings have robustly shown the futility of simvastatin for slowing motor progression in moderate severity Parkinson's disease patients, providing no evidence to support proceeding to a phase 3 trial," the researchers wrote in their study. "The relationship between PD and cardiovascular factors is complicated."
Reference:
Stevens KN, Creanor S, Jeffery A, et al. Evaluation of Simvastatin as a Disease-Modifying Treatment for Patients With Parkinson Disease: A Randomized Clinical Trial. JAMA Neurol. Published online October 31, 2022. doi:10.1001/jamaneurol.2022.3718
