Statins and immune-mediated necrotizing myopathy: Variability in the risk

Thierry Trenque; Jed Hadjoudj; Agathe Trenque; Federica Tralongo; Salomé Martin; Brahim Azzouz

doi:10.1016/j.therap.2023.07.005

Statins and immune-mediated necrotizing myopathy: Variability in the risk

Therapie. 2023 Jul 30:S0040-5957(23)00106-3. doi: 10.1016/j.therap.2023.07.005. Online ahead of print.

Authors

Thierry Trenque¹, Jed Hadjoudj², Agathe Trenque², Federica Tralongo², Salomé Martin², Brahim Azzouz³

Affiliations

¹ Reims University Hospitals, Regional Centre for Pharmacovigilance and Pharmacoepidemiology, 51092 Reims, France; University of Reims Champagne-Ardenne, Faculty of Medicine, EA 3797, 51095 Reims, France. Electronic address: ttrenque@chu-reims.fr.
² Reims University Hospitals, Regional Centre for Pharmacovigilance and Pharmacoepidemiology, 51092 Reims, France.
³ Reims University Hospitals, Regional Centre for Pharmacovigilance and Pharmacoepidemiology, 51092 Reims, France; University of Reims Champagne-Ardenne, Faculty of Medicine, EA 3797, 51095 Reims, France.

PMID: 37625939
DOI: 10.1016/j.therap.2023.07.005

Abstract

Introduction: Immune-mediated necrotizing myopathy (IMNM) is a form of statin myopathy characterized by the presence of antibodies against 3-hydroxy-3-methylglutaryl-coenzyme A reductase (anti HMGCR).

Objectives: The aim of this study was to investigate the relationship between the different statins and the risk of IMNM.

Methods: A two-time approach was used. First, we performed a descriptive analysis of the French national pharmacovigilance database (FNPV) for the period from 1985 to december2020. To identify relevant cases, we used Medical Dictionary for Regulatory Activities (MedDRA) preferred terms (PTs) related to IMNM. We performed a quantitative and qualitative review of individual case safety reports (ICSRs) recorded in the french vigilance spontaneous reporting system. In a second time, we performed a comparative analysis with the World Health Organization global individual case safety reports database (Vigibase). The association between IMNM and statins exposure was assessed by calculating the reporting odds ratio (ROR) and its 95% confidence interval.

Results: After analysis, a total of 25 ICSRs were related to IMNM in the FNPV. The suspected statins were atorvastatin (n=21), simvastatin (n=2), pravastatin (n=1) and rosuvastatin (n=1). In Vigibase, 567 notifications were identified. A significant ROR value was found for atorvastatin, pitavastatin, simvastatin, pravastatin and rosuvastatin.

Conclusion: Atorvastatin presents the highest risk of IMNM. Our data suggest that the occurrence of IMNM is a class effect.

Keywords: Antibodies; Myopathy; Pharmacovigilance; Risk; Statins.