Yerolatsite Melina, Torounidou Nanteznta, Gerolymatou Nafsika, Panteli Aikaterini, Koletsos Nikolaos, Karakosta Maria, Zarkavelis George, Voulgari Paraskevi V
Department of Medical Oncology, School of Health Sciences, Faculty of Medicine, University of Ioannina, Ioannina, Greece.
Department of Rheumatology, School of Health Sciences, Faculty of Medicine, University of Ioannina, 45110, Ioannina, Greece.
Rheumatol Int. 2025 Apr 18;45(5):109. doi: 10.1007/s00296-025-05860-0.
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.
免疫介导性坏死性肌病（IMNM）是一种炎性肌病，与抗信号识别颗粒（anti-SRP）抗体或抗3-羟基-3-甲基戊二酰辅酶A还原酶（抗HMGCR）抗体相关，他汀类药物的使用可能由于靶向HMGCR而诱发他汀类药物相关的IMNM（SAIMNM）。前蛋白转化酶枯草溶菌素/kexin 9型（PCSK9）抑制剂可能为这些患者提供更安全的降脂替代方案。本研究旨在描述SAIMNM患者的临床特征，并评估肌炎发作后PCSK9抑制剂的安全性。我们介绍了5例SAIMNM患者的临床特征，并评估了PCSK9抑制剂在这些病例中的安全性。此外，我们使用四个不同的数据库（Medline/PubMed、Scopus、Cochrane和DOAJ）进行了文献综述，以总结关于IMNM的现有数据。虽然众多文章讨论了他汀类药物引起的肌炎，但我们仅选择了那些涉及IMNM治疗后血脂异常治疗的研究。所有5例患者均为女性，其中4例有他汀类药物使用史。1例未使用过他汀类药物的患者抗SRP抗体呈阳性，其他患者抗HMGCR抗体呈阳性。平均随访18.2个月后，肌酸磷酸激酶（CPK）水平从1028.6 IU/L降至135 IU/L，低密度脂蛋白胆固醇水平从206.2 mg/dL降至87.2 mg/dL。所有患者均接受了类固醇治疗（剂量逐渐减少），5例患者中有4例接受了二线免疫抑制治疗，如静脉注射免疫球蛋白、甲氨蝶呤、硫唑嘌呤和霉酚酸酯。开始使用PCSK9抑制剂后未发生疾病复发。对7项研究（15例患者）的综述显示，平均CPK为1531.9 IU/L。40%的患者接受了类固醇和另一种免疫抑制剂治疗。他汀类药物再次激发试验在2例患者中导致复发，但PCSK9抑制剂耐受性良好，只有1例患者需要额外的免疫抑制治疗。此外，依折麦布和贝派地酸在一些患者中成功使用。最后，使用PCSK9抑制剂治疗后血脂水平似乎更低。对于IMNM患者，PCSK9抑制剂的给药似乎是治疗血脂异常的一种有效且安全的选择。
