| 16 | 0 | 11 |
| 下载次数 | 被引频次 | 阅读次数 |
目的 分析探讨依洛尤单抗与阿利西尤单抗所致药品不良反应（ADR）的发生情况与临床特征，为促进临床合理用药提供依据。方法 检索中国知网、万方、维普、PubMed和Web of Science数据库中依洛尤单抗和阿利西尤单抗导致ADR的病例报道，检索时限为2015年7月至2024年2月，提取病例性别、年龄、原发疾病与合并症、依洛尤单抗与阿利西尤单抗的用法用量、ADR类型、ADR发生时间、ADR处理与转归等信息。结果 纳入病例报道16篇，包括17例病例，年龄（61.9±15.2）岁，28～81岁，其中年龄为61～90岁的病例占比最高（占70.6%）。17例病例中有合并症的有11例（占64.7%），有合并用药的有7例（占41.2%），合并用药均为慢性疾病治疗用药。17例病例的给药途径、适应证和给药剂量均与药品说明书相符。ADR发生的时间主要集中在用药后1～15 d（占52.9%），主要表现为皮肤及软组织损害、呼吸系统障碍及全身性损害等。16例病例经停药或对症处理后ADR好转或治愈，1例病例在主动脉植入术后因反复感染而死亡。结论 临床使用依洛尤单抗与阿利西尤单抗时须密切监测ADR，特别是对于高龄患者，发生ADR后须及时处理，保障患者的用药安全。
Abstract：AIM To analyze the occurrence and clinical characteristics of adverse reactions(ADR) caused by evolocumab and alirocumab, to provide a basis for promoting rational clinical medication. METHODS Case literature on ADR caused by evolocumab and alirocumab was screened and analyzed by searching CNKI databases, Wanfang databases, VIP databases, PubMed, and Web of Science from July 2015 to February 2024. The extracted data included patient sex, age, primary diseases and comorbidities, administration details(dosage and regimen) of evolocumab/alirocumab, type of ADR, time to ADR onset, management of ADR, and patient outcomes. RESULTS A total of 16 literature reports on ADR were retrieved, with 17 patients included. Patients had a mean age of 61.9 ± 15.2 years, with ages ranging from 28 to 81 years. The age group with the highest proportion was 61-90 years, accounting for 70.6%. Comorbidities were present in 11 patients(64.7%), and concomitant medications(all indicated for chronic conditions) were used in 7 patients(41.2%). The route of administration, indications, and dosages of the implicated drugs were consistent with prescribing information. The occurrence of ADR mainly occurred within 1-15 days(52.9%), mainly involving skin and soft tissue, respiratory system disorders and systemic damage. ADR resolved or improved following drug discontinuation or symptomatic treatment in 16 patients; one patient died due to recurrent infection after aortic implantation, unrelated to the ADR.CONCLUSION During clinical use of evolocumab and alirocumab, close monitoring for ADR is essential, especially in elderly patients. Timely discontinuation and management should be ensured upon occurrence to enhance patients' medication safety.
[1] BONACA M P, NAULT P, GIUGLIANO R P, et al. Low-density lipoprotein cholesterol lowering with evolocumab and outcomes in patients with peripheral artery disease:insights from the FOURIER trial(further cardiovascular outcomes research with PCSK9inhibition in subjects with elevated risk)[J]. Circulation, 2018,137(4):338.
[2] AHAMAD S, MATHEW S, KHAN W A, et al. Development of small-molecule PCSK9 inhibitors for the treatment of hypercholesterolemia[J]. Drug Discovery Today, 2022, 27(5):1332.
[3] FITZGERALD G, KIERNAN T. PCSK9 inhibitors and LDL reduction:pharmacology, clinical implications, and future perspectives[J]. Expert Rev Cardiovas, 2018, 16(8):567.
[4] O’DONOGHUE M L, GIUGLIANO R P, WIVIOTT S D, et al.Long-term evolocumab in patients with established atherosclerotic cardiovascular disease[J]. Circulation, 2022, 146(15):1109.
[5] JI C M, BAI J M, ZHOU J C, et al. Adverse event profiles of PCSK9 inhibitors alirocumab and evolocumab:data mining of the FDA adverse event reporting system[J]. Br J Clin Pharmacol,2022, 88(12):5317.
[6] TANTIKUL C, DHANA N, JONGJAREARNPRASERT K, et al. The utility of the World Health Organization-The Uppsala Monitoring Centre(WHO-UMC)system for the assessment of adverse drug reactions in hospitalized children[J]. Asian Pac J Allergy Immunol, 2008, 26(2-3):77.
[7] FAHY E F, MCCARTHY E, STEINHAGEN-THIESSEN E, et al.A case of autosomal recessive hypercholesterolemia responsive to proprotein convertase subtilisin/kexin 9 inhibition[J]. J Clin Lipidol, 2017, 11(1):287.
[8] JHAVERI K D, BARTA V S, PULLMAN J. Praluent(alirocumab)-induced renal injury[J]. J Pharm Pract, 2017, 30(1):7.
[9] BENEDICT P A, ABDOU R M, DION G R, et al. Association of alirocumab therapy with inflammatory lesions of the vocal folds:a case report[J]. Laryngoscope, 2017, 127(7):1652.
[10] MEMON R, MALEK R, MUNIR K M. Doubling of hemoglobin A1c on PCSK9 inhibitor therapy[J]. Am J Med, 2019, 132(1):e17.
[11] KANDA N, OKAJIMA F. Atopic dermatitis-like rash during evolocumab treatment of familial hypercholesterolemia[J]. J Nippon Med Sch, 2019, 86(3):187.
[12] ST?LLBERGER C, MERTIKIAN G, STAHL D, et al. Fatal recurrent Staphylococcus aureus infection in a patient with an aortic endostent under alirocumab[J]. Infect Dis(Auckl), 2019,12:1178633719885387.
[13] THERMOS G, TOSIOS K I. Gingival ischemia and petechiae in a patient medicated with PCSK9 inhibitor for hypercholesterolemia:an adverse drug event?[J]. Clin Adv Periodontics, 2019, 9(1):20.
[14] INOUE I, TAKENAKA Y, KIN Y, et al. A sudden onset of severe thrombocytopenia while using evolocumab[J]. Case Rep Hematol, 2020, 2020:3281626.
[15] A L K H AT I B A A , A N G L A D E P. A l i r o c u m a b-i n d u c e d hyperlipasemia and hyperamylasemia[J]. Ann Pharmacother,2020, 54(7):720.
[16] BREAZZANO M P, CHEN R W S. Scleritis with uveal effusion from alirocumab[J]. Ann Intern Med, 2020, 172(12):834.
[17] LAM S S Y, CHIANG V, LAM K, et al. First confirmed case of IgE-mediated hypersensitivity to evolucumab with cross-reactivity to alirocumab[J]. J Allergy Clin Immunol Pract, 2021, 9(9):3481.
[18] ABDELMASEIH R, ABDELMASIH R, HASAN M, et al. Atrial fibrillation as a possible adverse reaction to evolocumab[J].Cureus, 2021, 13(6):e15467.
[19] GHERNAUTAN V, AMINI M, SACHMECHI I. Maculopapular exanthema after the second dose of evolocumab[J]. Cureus,2021, 13(5):e15249.
[20] B?R S, R?BER I, KOSKINAS K C, et al. Transient injection site reaction to alirocumab during immune system activation:a case series[J]. Eur Heart J Case Rep, 2022, 6(5):ytac187.
[21] ALLEVI M, SARNARI S, GIULIETTI F, et al. Painful and recurring injection site reaction to alirocumab and evolocumab in a young woman with familial hypercholesterolemia and effective therapeutic alternative based on inclisiran:a case report[J].Front Cardiovasc Med, 2023, 10:1181720.
[22] SALEH K, BADAW AKI H, BAZ M, et al. First report of an evolocumab induced nephrotic syndrome[J]. Nephrol Dial Transpl, 2023, 38:403.
[23] SABATINE M S, GIUGLIANO R P, KEECH A C, et al.Evolocumab and clinical outcomes in patients with cardiovascular disease[J]. N Engl J Med, 2017, 376(18):1713.
[24]李颖，王远敏.基于FAERS数据库的他汀类药物血糖相关不良反应事件信号挖掘[J].临床合理用药，2024,17(14):1.
[25] AVENA-WOODS C. Overview of atopic dermatitis[J]. Am J Manag Care, 2017, 23(8 suppl):S115.
[26] SROKA-TOMASZEWSKA J, TRZECIAK M. Molecular mechanisms of atopic dermatitis pathogenesis[J]. Int J Mol Sci,2021, 22(8):4130.
[27] KRISHNA M, NADLER S G. Immunogenicity to biotherapeuticsthe role of anti-drug immune complexes[J]. Front Immunol,2016, 7:21.
[28] KAM T, ALEXANDER M. Drug-induced immune thrombocytopenia[J]. J Pharm Pract, 2014, 27(5):430.
[29] PACIULLO F, MOMI S, GRESELE P. PCSK9 in haemostasis and thrombosis:possible pleiotropic effects of PCSK9 inhibitors in cardiovascular prevention[J]. Thromb Haemost, 2019, 119(3):359.
基本信息:
DOI：10.19577/j.1007-4406.2025.09.009
中图分类号:R969.3
引用信息:
[1]裴亚敏,申梦丽.依洛尤单抗与阿利西尤单抗致不良反应文献分析[J].中国临床药学杂志,2025,34(09):692-696.DOI:10.19577/j.1007-4406.2025.09.009.
基金信息: