Dirk Essers1,2, Martina Schäublin1, Gerd A Kullak-Ublick2, Stefan Weiler3,4. 1. Swissmedic, Swiss Agency for Therapeutic Products, Bern, Switzerland. 2. Department of Clinical Pharmacology and Toxicology and Regional Pharmacovigilance Centre, University Hospital Zurich, University of Zurich, Zurich, Switzerland. 3. Department of Clinical Pharmacology and Toxicology and Regional Pharmacovigilance Centre, University Hospital Zurich, University of Zurich, Zurich, Switzerland. stefan.weiler@usz.ch. 4. National Poisons Centre, Tox Info Suisse, Associated Institute of the University of Zurich, Zurich, Switzerland. stefan.weiler@usz.ch.
Abstract
PURPOSE: Statins represent an effective treatment for hyperlipidaemia. Immune-mediated necrotising myopathy (IMNM), a form of statin myopathy, has recently been described, and is characterized by elevated creatine kinase, presence of antibodies against HMG-CoA and no improvement after drug discontinuation, even with immunosuppressive treatment. Information on IMNM is mainly from case reports and small case series. Therefore, all reported cases of IMNM in VigiBase, the WHO global database of individual case safety reports (ICSRs) including the underlying reporting patterns, were analysed to characterize more detailed this adverse drug reaction. METHODS: ICSRs of IMNM up to October 1, 2016 were extracted from VigiBase. Corresponding case narratives were requested from responsible national authorities to maximize the available data. The reports were analysed in terms of reporting criteria, co-reported terms, patient demographics, clinical data, administered medication, latency time, seriousness of the reaction and outcome. RESULTS: One hundred one deduplicated ICSRs of IMNM were reported from 17 countries until October 2016. Approximately two thirds of the cases were from the year 2016. Slightly more males than females were affected (52 [57%] males vs 39 [42%] females). Median reported patient age was 68 years (range 16 - 87 years). Ninety-one cases (99%) were classified as serious. Median latency time was 26 months (range 1 - 288 months). Median creatine kinase value was 6860 U/L (range 576 - 35,000 U/L). In total, eight patients (9%) had recovered from IMNM. Atorvastatin was the most frequently reported statin in 80% of cases. CONCLUSIONS: The number of IMNM reports has increased in recent years. IMNM associated with statin treatment seems to occur worldwide. Most IMNM cases were reported with atorvastatin. No dose dependency of statin-associated IMNM pathogenesis was identified.
PURPOSE: Statins represent an effective treatment for hyperlipidaemia. Immune-mediated necrotising myopathy (IMNM), a form of statin myopathy, has recently been described, and is characterized by elevated creatine kinase, presence of antibodies against HMG-CoA and no improvement after drug discontinuation, even with immunosuppressive treatment. Information on IMNM is mainly from case reports and small case series. Therefore, all reported cases of IMNM in VigiBase, the WHO global database of individual case safety reports (ICSRs) including the underlying reporting patterns, were analysed to characterize more detailed this adverse drug reaction. METHODS: ICSRs of IMNM up to October 1, 2016 were extracted from VigiBase. Corresponding case narratives were requested from responsible national authorities to maximize the available data. The reports were analysed in terms of reporting criteria, co-reported terms, patient demographics, clinical data, administered medication, latency time, seriousness of the reaction and outcome. RESULTS: One hundred one deduplicated ICSRs of IMNM were reported from 17 countries until October 2016. Approximately two thirds of the cases were from the year 2016. Slightly more males than females were affected (52 [57%] males vs 39 [42%] females). Median reported patient age was 68 years (range 16 - 87 years). Ninety-one cases (99%) were classified as serious. Median latency time was 26 months (range 1 - 288 months). Median creatine kinase value was 6860 U/L (range 576 - 35,000 U/L). In total, eight patients (9%) had recovered from IMNM. Atorvastatin was the most frequently reported statin in 80% of cases. CONCLUSIONS: The number of IMNM reports has increased in recent years. IMNM associated with statin treatment seems to occur worldwide. Most IMNM cases were reported with atorvastatin. No dose dependency of statin-associated IMNM pathogenesis was identified.
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