The Effectiveness of Statins as Potential Therapy for Multiple Sclerosis: A Systematic Review of Randomized Controlled trials

Evidence of the effectiveness of statins, the lipid-lowering agents in retarding the progression of Multiple Sclerosis (MS), a disabling neurological disease with autoimmune etiology, have been highlighted in animal studies and observational studies. The proposed immune-modulatory actions and neuroprotective effects of statins make them a promising treatment option for MS that needs to be explored further. In this systematic review, we aim to investigate the role of different statins as monotherapy or in combination with the established MS medications in improving the clinical and radiological course of MS variants, including optic neuritis, using randomized controlled trials (RCTs). We systematically searched PubMed, PubMed Central (PMC), MEDLINE, Cochrane library, and Scopus databases using regular keywords and medical subject headings terms. Randomized controlled trials of any statin used in any variants of MS, including studies on statins used in optic neuritis published up to April 2021, were included in the review. Data on the effects on the relapse rate, the Expanded Disability Status Scale (EDSS) alterations, and the changes in Magnetic Resonance Imaging (MRI) lesions were collected from the included studies. Seven studies with a total of 831 patients and an average duration of follow-up of six to 36 months were included in our review. Five trials were of statins add-on to interferon therapy in relapsing-remitting multiple sclerosis (RRMS), of which four studies were assessed to be of good quality while the remaining study featured a high risk of bias. One trial of simvastatin monotherapy in Secondary Progressive Multiple Sclerosis (SPMS) was included, which was assessed to be of good methodological quality with low risk of bias and adequate patient number. A trial of simvastatin monotherapy on patients with optic neuritis was included, which was evaluated as a good quality study. Still, it had a low number of participants and a short duration of follow-up. We used the changes in disease relapse rate and EDSS as primary outcome variables and the MRI lesions changes as a secondary outcome variable. Studies in RRMS showed no significant effects on primary and secondary outcomes. The study on SPMS featured a significant improvement in EDSS in simvastatin-treated patients with no effect on relapse rate or MRI changes. Simvastatin use in optic neuritis enhances clinical visual outcomes with no significant effect on MRI changes or the rate of progression to definite MS. In contrast to animal studies and observational studies, randomized controlled trials do not replicate the positive effects of statins used as monotherapy or combined with interferon beta in patients with RRMS and optic neuritis in relapse rate EDSS or MRI changes. However, trials of statins on SPMS showed a promising effect on disability progression (EDSS score), which might support the proposed immune-modulatory and neuroprotective role of statins and serve as a baseline for further RCTs applying statins as monotherapy or combination with other established MS therapies.