The effects of HMG-CoA reductase inhibitors on disease activity in multiple sclerosis: A systematic review and meta-analysis

• Published in: Multiple sclerosis and related disorders 2022-02, Vol.58, p.103395-103395, Article 103395
• Main Authors: Stefanou, Maria-Ioanna, Palaiodimou, Lina, Katsanos, Aristeidis H., Milionis, Haralampos, Kosmidou, Maria, Lambadiari, Vaia, Halvatsiotis, Panagiotis, Ferentinos, Panagiotis, Andreadou, Elizabeth, Marinos, Georgios, Theodorou, Aikaterini, Tzartos, John S, Voumvourakis, Konstantinos, Tsivgoulis, Georgios, Giannopoulos, Sotirios
• Format: Article
• Language: English
• Subjects: Disease activity; HMG-COA reductase inhibitors; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; Interferon-beta - therapeutic use; Multiple sclerosis; Multiple Sclerosis - drug therapy; Multiple Sclerosis - pathology; Multiple Sclerosis, Chronic Progressive - drug therapy; Multiple Sclerosis, Relapsing-Remitting - diagnostic imaging; Multiple Sclerosis, Relapsing-Remitting - drug therapy; Multiple Sclerosis, Relapsing-Remitting - pathology; pleiotropic effects; Randomized Controlled Trials as Topic; Statins
• ISSN: 2211-0348; 2211-0356
• DOI: 10.1016/j.msard.2021.103395

•In RRMS we detected no benefit from statin treatment as add-on to IFN-β.•Combination of statins with IFN-β was safe and well-tolerated.•Potential beneficial effects in SPMS, CIS and ON warrant further evaluation in future RCTs. To assess whether statins (3‑hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) exert disease-modifying effects in multiple sclerosis (MS). A systematic review and meta-analysis was performed including randomized-controlled clinical trials (RCTs) on statin use in MS. A random-effects model was applied to calculate pooled estimates and odds ratios (ORs) with corresponding 95% confidence intervals (CIs), when comparing patients treated with statins alone or adjunct to disease modifying treatment (DMT) to non-statin-treated patients. We identified 7 RCTs including 789 patients with relapsing-remitting MS (RRMS), all of whom received additional DMT with IFN-β. Single identified RCTs in secondary-progressive MS (SPMS), clinically isolated syndrome (CIS) and optic neuritis (ON) were not meta-analyzed. In RRMS, add-on statin use was not associated with the risk of clinical relapse (OR=1.30, 95%CI: 0.901.87) or EDSS-progression from baseline, neither appeared related to the risk of new contrast-enhancing or T2 lesions (OR=1.28, 95%CI: 0.364.58), and the risk of whole-brain volume reduction on MRI. Add-on statins to IFN-β were safe and well-tolerated. In SPMS, stand-alone simvastatin led to significantly reduced annualized rate of whole-brain volume reduction. In CIS and ON, statins were associated with reduced risk for new T2 lesions and improved visual recovery, respectively. We detected no benefit from statin treatment as add-on to IFN-β in RRMS. However, a potential beneficial effect in SPMS, CIS and ON deserves independent confirmation and further evaluation within adequately powered RCTs.