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<p>Immune-mediated necrotizing myopathy (IMNM), a type of inflammatory myopathy, is associated with anti-SRP or anti-3-hydroxy-3-methylglutaryl coenzyme A reductase (anti-HMGCR) antibodies, with statin use potentially inducing statin-associated IMNM (SAIMNM) due to HMGCR targeting. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors may offer a safer alternative for lipid-lowering in these patients. This study aims to describe the clinical characteristics of SAIMNM patients and evaluate the safety of PCSK9 inhibitors after myositis onset. We present the clinical characteristics of five SAIMNM patients and evaluate the safety of PCSK9 inhibitors in these cases. Additionally, we conducted a literature review using four different databases (Medline/PubMed, Scopus, Cochrane and DOAJ) to summarize the available data on IMNM. While numerous articles discussed statin-induced myositis, we selected only those studies that addressed the treatment of dyslipidemia after the management of IMNM. All five patients were women, with four having a history of statin use. One statin-naïve patient was positive for anti-SRP antibodies, while the others had anti-HMGCR antibodies. After a mean follow-up of 18.2&#xa0;months, creatine phosphokinase (CPK) levels dropped from 1028.6&#xa0;IU/L to 135&#xa0;IU/L, and LDL cholesterol levels decreased from 206.2&#xa0;mg/dL to 87.2&#xa0;mg/dL. All patients were treated with steroids (with a gradual dosage reduction), and four of the five received second line immunosuppressive therapy, such as intravenous immunoglobulin, methotrexate, azathioprine, and mycophenolate mofetil. No disease recurrence occurred after starting PCSK9 inhibitors. A review of seven studies (15 patients) showed a mean CPK of 1531.9&#xa0;IU/L. 40% received steroids and another immunosuppressant. Statin rechallenge caused relapse in two cases, but PCSK9 inhibitors were well tolerated, with only one patient needing additional immunosuppression. Additionally, ezetimibe and bempedoic acid were used successfully in some patients. Finally, lipid levels appeared to be lower after treatment with PCSK9 inhibitors. Administration of PCSK9 inhibitors appears to be an effective and safe option for the treatment of dyslipidaemia in patients with IMNM.</p>

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Effectiveness of proprotein convertase subtilisin/kexin type 9 inhibitors in managing hypercholesterolemia post-statin-associated immune-mediated necrotizing myopathy: report of five cases and literature review

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年4月18日

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  • Melina Yerolatsite,
  • Nanteznta Torounidou,
  • Nafsika Gerolymatou,
  • Aikaterini Panteli,
  • Nikolaos Koletsos,
  • Maria Karakosta,
  • George Zarkavelis,
  • Paraskevi V. Voulgari

摘要

Immune-mediated necrotizing myopathy (IMNM), a type of inflammatory myopathy, is associated with anti-SRP or anti-3-hydroxy-3-methylglutaryl coenzyme A reductase (anti-HMGCR) antibodies, with statin use potentially inducing statin-associated IMNM (SAIMNM) due to HMGCR targeting. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors may offer a safer alternative for lipid-lowering in these patients. This study aims to describe the clinical characteristics of SAIMNM patients and evaluate the safety of PCSK9 inhibitors after myositis onset. We present the clinical characteristics of five SAIMNM patients and evaluate the safety of PCSK9 inhibitors in these cases. Additionally, we conducted a literature review using four different databases (Medline/PubMed, Scopus, Cochrane and DOAJ) to summarize the available data on IMNM. While numerous articles discussed statin-induced myositis, we selected only those studies that addressed the treatment of dyslipidemia after the management of IMNM. All five patients were women, with four having a history of statin use. One statin-naïve patient was positive for anti-SRP antibodies, while the others had anti-HMGCR antibodies. After a mean follow-up of 18.2 months, creatine phosphokinase (CPK) levels dropped from 1028.6 IU/L to 135 IU/L, and LDL cholesterol levels decreased from 206.2 mg/dL to 87.2 mg/dL. All patients were treated with steroids (with a gradual dosage reduction), and four of the five received second line immunosuppressive therapy, such as intravenous immunoglobulin, methotrexate, azathioprine, and mycophenolate mofetil. No disease recurrence occurred after starting PCSK9 inhibitors. A review of seven studies (15 patients) showed a mean CPK of 1531.9 IU/L. 40% received steroids and another immunosuppressant. Statin rechallenge caused relapse in two cases, but PCSK9 inhibitors were well tolerated, with only one patient needing additional immunosuppression. Additionally, ezetimibe and bempedoic acid were used successfully in some patients. Finally, lipid levels appeared to be lower after treatment with PCSK9 inhibitors. Administration of PCSK9 inhibitors appears to be an effective and safe option for the treatment of dyslipidaemia in patients with IMNM.