贝利尤单抗用于儿童系统性红斑狼疮的研究进展

邓伟萍

doi:10.7499/j.issn.1008-8830.2107153

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中国当代儿科杂志 ›› 2021, Vol. 23 ›› Issue (10) : 1069-1074. DOI: 10.7499/j.issn.1008-8830.2107153

综述

贝利尤单抗用于儿童系统性红斑狼疮的研究进展

邓伟萍¹

作者信息 +

Recent advances in the treatment of systemic lupus erythematosus with belimumab in children

DENG Wei-Ping

Author information +

文章历史 +

摘要

系统性红斑狼疮（systemic lupus erythematosus，SLE）是一种累及多器官的自身免疫性疾病，狼疮肾炎（lupus nephritis，LN）是其最常见的肾脏并发症。贝利尤单抗是一种完全人源化的单克隆抗体，可减少B细胞的数量，从而减少自身抗体的形成。贝利尤单抗可改善成人和儿童SLE反应指数、SLE疾病活动度评分，延缓LN的进展，对SLE及LN的治疗具有重要作用。该文综述了国内外贝利尤单抗用于治疗儿童和成人SLE的相关研究报道，并分析了其在儿童患者中的有效性及安全性，以期能对贝利尤单抗临床应用于儿童SLE的治疗提供有效的参考价值。

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple organs, and lupus nephritis (LN) is the most common renal complication of SLE. Belimumab is a fully humanized monoclonal antibody that can reduce the number of B cells, thereby reducing the formation of autoantibodies. Belimumab can improve SLE response index and SLE disease activity score and delay the progression of LN in both adults and children and thus plays an important role in the treatment of SLE and LN. This article reviews related research reports of belimumab used in the treatment of children and adults with SLE in China and overseas and analyzes the efficacy and safety of belimumab in pediatric patients, in order to provide a reference for the clinical application of belimumab in children with SLE.

导出引用

邓伟萍. 贝利尤单抗用于儿童系统性红斑狼疮的研究进展[J]. 中国当代儿科杂志. 2021, 23(10): 1069-1074 https://doi.org/10.7499/j.issn.1008-8830.2107153

DENG Wei-Ping. Recent advances in the treatment of systemic lupus erythematosus with belimumab in children[J]. Chinese Journal of Contemporary Pediatrics. 2021, 23(10): 1069-1074 https://doi.org/10.7499/j.issn.1008-8830.2107153

参考文献

1 Harry O, Yasin S, Brunner H. Childhood-onset systemic lupus erythematosus: a review and update[J]. J Pediatr, 2018, 196: 22-30.e2. PMID: 29703361. DOI: 10.1016/j.jpeds.2018.01.045.
2 Lockshin MD, Barbhaiya M, Izmirly P, et al. SLE: reconciling heterogeneity[J]. Lupus Sci Med, 2019, 6(1): e000280. PMID: 31080630. PMCID: PMC6485210. DOI: 10.1136/lupus-2018-000280.
3 Silva CA, Avcin T, Brunner HI. Taxonomy for systemic lupus erythematosus with onset before adulthood[J]. Arthritis Care Res (Hoboken), 2012, 64(12): 1787-1793. PMID: 22730317. PMCID: PMC3463746. DOI: 10.1002/acr.21757.
4 Fanouriakis A, Kostopoulou M, Alunno A, et al. 2019 update of the EULAR recommendations for the management of systemic lupus erythematosus[J]. Ann Rheum Dis, 2019, 78(6): 736-745. PMID: 30926722. DOI: 10.1136/annrheumdis-2019-215089.
5 Al Sawah S, Zhang X, Zhu BJ, et al. Effect of corticosteroid use by dose on the risk of developing organ damage over time in systemic lupus erythematosus—the Hopkins Lupus Cohort[J]. Lupus Sci Med, 2015, 2(1): e000066. PMID: 25861455. PMCID: PMC4378372. DOI: 10.1136/lupus-2014-000066.
6 Kleinmann JF, Tubach F, Le Guern V, et al. International and multidisciplinary expert recommendations for the use of biologics in systemic lupus erythematosus[J]. Autoimmun Rev, 2017, 16(6): 650-657. PMID: 28434948. DOI: 10.1016/j.autrev.2017.04.011.
7 Tsokos GC, Lo MS, Reis PC, et al. New insights into the immunopathogenesis of systemic lupus erythematosus[J]. Nat Rev Rheumatol, 2016, 12(12): 716-730. PMID: 27872476. DOI: 10.1038/nrrheum.2016.186.
8 Tipton CM, Hom JR, Fucile CF, et al. Understanding B-cell activation and autoantibody repertoire selection in systemic lupus erythematosus: a B-cell immunomics approach[J]. Immunol Rev, 2018, 284(1): 120-131. PMID:29944759. PMCID:PMC6022284. DOI: 10.1111/imr.12660.
9 Baker KP, Edwards BM, Main SH, et al. Generation and characterization of lymphostat-B, a human monoclonal antibody that antagonizes the bioactivities of B lymphocyte stimulator[J]. Arthritis Rheum, 2003, 48(11): 3253-3265. PMID: 14613291. DOI: 10.1002/art.11299.
10 Guzman M, Hui-Yuen JS. Management of pediatric systemic lupus erythematosus: focus on belimumab[J]. Drug Des Devel Ther, 2020, 14: 2503-2513. PMID: 32612353. PMCID: PMC7323799. DOI: 10.2147/DDDT.S216193.
11 佚名. 葛兰素贝利尤单抗(Belimumab)进口注册申请获国家药监批准[J]. 临床合理用药杂志, 2019, 12(20): 72.
12 Levy RA, Gonzalez-Rivera T, Khamashta M, et al. 10 Years of belimumab experience: what have we learnt?[J]. Lupus, 2021.PMID: 34238087. DOI: 10.1177/09612033211028653. Epub ahead of print.
13 Brunner HI, Abud-Mendoza C, Viola DO, et al. Safety and efficacy of intravenous belimumab in children with systemic lupus erythematosus: results from a randomised, placebo-controlled trial[J]. Ann Rheum Dis, 2020, 79(10): 1340-1348. PMID: 32699034. PMCID: PMC7509523. DOI: 10.1136/annrheumdis-2020-217101.
14 罗蕾, 黄文瀚, 任飞凤, 等. 7例贝利尤单抗治疗系统性红斑狼疮的有效性和安全性分析[J]. 重庆医科大学学报, 2021, 1-4. DOI: 10.13406/j.cnki.cyxb.002732.
15 Navarra SV, Guzmán RM, Gallacher AE, et al. Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, phase 3 trial[J]. Lancet, 2011, 377(9767): 721-731. PMID: 21296403. DOI: 10.1016/S0140-6736(10)61354-2.
16 Furie R, Petri M, Zamani O, et al. A phase III, randomized, placebo-controlled study of belimumab, a monoclonal antibody that inhibits B lymphocyte stimulator, in patients with systemic lupus erythematosus[J]. Arthritis Rheum, 2011, 63(12): 3918-3930. PMID: 22127708. PMCID: PMC5007058. DOI: 10.1002/art.30613.
17 Wallace DJ, Ginzler EM, Merrill JT, et al. Safety and efficacy of belimumab plus standard therapy for up to thirteen years in patients with systemic lupus erythematosus[J]. Arthritis Rheum, 2019, 71(7): 1125-1134. PMID: 30771238. PMCID: PMC6617785. DOI: 10.1002/art.40861.
18 Iaccarino L, Andreoli L, Bocci EB, et al. Clinical predictors of response and discontinuation of belimumab in patients with systemic lupus erythematosus in real life setting. Results of a large, multicentric, nationwide study[J]. J Autoimmun, 2018, 86: 1-8. PMID: 28935492. DOI: 10.1016/j.jaut.2017.09.004.
19 Tanaka Y, Bae SC, Bass D, et al. Long-term open-label continuation study of the safety and efficacy of belimumab for up to 7 years in patients with systemic lupus erythematosus from Japan and South Korea[J]. RMD Open, 2021, 7(2): e001629. PMID: 34215703. PMCID: PMC8256836. DOI: 10.1136/rmdopen-2021-001629.
20 Suso JP, Posso-Osorio I, Jiménez CA, et al. Profile of BAFF and its receptors' expression in lupus nephritis is associated with pathological classes[J]. Lupus, 2018, 27(5): 708-715. PMID: 29087261. DOI: 10.1177/0961203317739132.
21 Hui-Yuen JS, Reddy A, Taylor J, et al. Safety and efficacy of belimumab to treat systemic lupus erythematosus in academic clinical practices[J]. J Rheumatol, 2015, 42(12): 2288-2295. PMID: 26523030. PMCID: PMC5031077. DOI: 10.3899/jrheum.150470.
22 Furie R, Rovin BH, Houssiau F, et al. Two-year, randomized, controlled trial of belimumab in lupus nephritis[J]. N Engl J Med, 2020, 383(12): 1117-1128. PMID: 32937045. DOI: 10.1056/NEJMoa2001180.
23 徐甜, 施璇, 谢筱彤, 等. 贝利尤单抗在一例活动性狼疮肾炎年轻女性患者中的应用[J]. 中华肾脏病杂志, 2021, 37(4): 366-368. DOI: 10.3760/cma.j.cn441217-20200707-00053.
24 Kraaij T, Arends EJ, van Dam LS, et al. Long-term effects of combined B-cell immunomodulation with rituximab and belimumab in severe, refractory systemic lupus erythematosus: 2-year results[J]. Nephrol Dial Transplant, 2021, 36(8): 1474-1483. PMID: 32591783. PMCID: PMC8311580. DOI: 10.1093/ndt/gfaa117.
25 Tarr T, Dérfalvi B, Gy?ri N, et al. Similarities and differences between pediatric and adult patients with systemic lupus erythematosus[J]. Lupus, 2015, 24(8): 796-803. PMID: 25516474. DOI: 10.1177/0961203314563817.
26 Zhang FC, Bae SC, Bass D, et al. A pivotal phase III, randomised, placebo-controlled study of belimumab in patients with systemic lupus erythematosus located in China, Japan and South Korea[J]. Ann Rheum Dis, 2018, 77(3): 355-363. PMID: 29295825. PMCID: PMC5867402. DOI: 10.1136/annrheumdis-2017-211631.
27 Ferreira JCOA , Trindade VC, Espada G, et al. Epidemiology and management practices for childhood-onset systemic lupus erythematosus patients: a survey in Latin America[J]. Clin Rheumatol, 2018, 37(12): 3299-3307. PMID: 30094748. DOI: 10.1007/s10067-018-4254-4.
28 Fontana F, Alfano G, Leonelli M, et al. Efficacy of belimumab for active lupus nephritis in a young Hispanic woman intolerant to standard treatment: a case report[J]. BMC Nephrol, 2018, 19(1): 276. PMID: 30342482. PMCID: PMC6196012. DOI: 10.1186/s12882-018-1066-3.
29 张涛, 李国民, 刘海梅, 等. 贝利尤单抗治疗儿童神经精神狼疮1例病例报告[J]. 中国循证儿科杂志, 2020, 15(5): 391-393. DOI: 10.3969/j.issn.1673-5501.2020.05.015.
30 朱万红, 王秀丽, 赵成广, 等. 贝利尤单抗治疗以呕吐尿频为首发症状的儿童系统性红斑狼疮一例[J]. 国际儿科学杂志, 2021, 48(3): 214-216. DOI: 10.3760/cma.j.issn.1673-4408.2021.03.016.
31 Dimelow R, Ji B, Struemper H. Pharmacokinetics of belimumab in children with systemic lupus erythematosus[J]. Clin Pharmacol Drug Dev, 2021, 10(6): 622-633. PMID: 33245847. PMCID: PMC8246766. DOI: 10.1002/cpdd.889.
32 Nino A, Bass DL, Eriksson G, et al. Efficacy and safety of intravenous belimumab in children with systemic lupus erythematosus: an across-trial comparison with the adult belimumab studies[J]. Arthritis Rheum, 2019, 71(suppl 10): 5083-5085.
33 Sheikh S, Scheinberg M, Wei JCC, et al. Headline results for a phase 4, 52-week, randomised, double-blind, placebo-controlled study to assess adverse envents of special interest (AESI) in adults with active, autoantibody-positive system lupus erythematosus (SLE) receiving belimumab[J]. Ann Rheum Dis, 2019, 78: 266.
34 佚名. 英国警示贝利木单抗严重精神不良事件发生增加的风险[J]. 中国医药导刊, 2019, 21(8): 487.
35 Wallace DJ, Navarra S, Petri MA, et al. Safety profile of belimumab: pooled data from placebo-controlled phase 2 and 3 studies in patients with systemic lupus erythematosus[J]. Lupus, 2013, 22(2): 144-154. PMID: 23213069. DOI: 10.1177/0961203312469259.
36 Fredericks CA, Kvam KA, Bear J, et al. A case of progressive multifocal leukoencephalopathy in a lupus patient treated with belimumab[J]. Lupus, 2014, 23(7): 711-713. PMID: 24531080. DOI: 10.1177/0961203314524292.
37 Leblanc-Trudeau C, Masetto A, Bocti C. Progressive multifocal leukoencephalopathy associated with belimumab in a patient with systemic lupus erythematosus[J]. J Rheumatol, 2015, 42(3): 551-552. PMID: 25729044. DOI: 10.3899/jrheum.140577.
38 Benvenuti F, Gatto M, Doria A. A case of progressive multifocal leukoencephalopathy in a lupus patient treated with belimumab—comments on article by Fredericks et al[J]. Lupus, 2014, 23(13): 1445-1446. PMID: 25107935. DOI: 10.1177/0961203314545800.
39 Fanouriakis A, Kostopoulou M, Cheema K, et al. 2019 Update of the Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of lupus nephritis[J]. Ann Rheum Dis, 2020, 79(6): 713-723. PMID: 32220834. DOI: 10.1136/annrheumdis-2020-216924.
40 中华医学会风湿病学分会, 国家皮肤与免疫疾病临床医学研究中心, 中国系统性红斑狼疮研究协作组. 2020中国系统性红斑狼疮诊疗指南[J]. 中华内科杂志, 2020, 59(3): 172-185. PMID: 32146743. DOI: 10.3760/cma.j.issn.0578-1426.2020.03.002.
41 Trindade VC, Carneiro-Sampaio M, Bonfa E, et al. An update on the management of childhood-onset systemic lupus erythematosus[J]. Paediatr Drugs, 2021, 23(4): 331-347. PMID: 34244988. PMCID: PMC8270778. DOI: 10.1007/s40272-021-00457-z.