Kostik Mikhail, Kalashnikova Elvira, Rinat Raupov, Isupova Eugenia, Gaidar Ekaterina, Soloviev Anton A, Masalova Vera, Snegireva Ludmila, Kornishina Tatyana, Abramova Natalia, Suspitsin Evgeny, Sorokina Lubov, Kaneva Maria, Dubko Margarita F, Lubimova Natalia, Kuchuinskaya Ekaterina, Kalashnikova Olga, Chasnyk Vyacheslav
Hospital Pediatry, Saint-Petersburg State Pediatric Medical University, 194100 Saint Petersburg, Russia.
Almazov National Medical Research Centre, 197341 Saint Petersburg, Russia.
Biomedicines. 2023 May 22;11(5):1503. doi: 10.3390/biomedicines11051503.
Pediatric lupus nephritis (LN) is one of the most serious manifestations of systemic lupus erythematosus (SLE) in children, determining the outcomes of the disease. There are no standardized treatment protocols for pediatric LN, and the role of biologics has not yet been conclusively defined.
analyze the safety and efficacy of rituximab biosimilar BCD020 in pediatric patients with lupus nephritis.
in a retrospective cohort study, the data from the case histories of 25 patients with LN (10 boys and 15 girls) with an onset age of 13 (9-16) years, who failed conventional non-biologic treatment or developed corticosteroid dependence/toxicity, were included. The diagnosis was made using Systemic Lupus International Collaborating Clinics (SLICC) classification criteria. Rituximab biosimilar BCD020 was prescribed in a dosage of 375 mg/m every week (2-4 infusions) with repeated courses every 6-12 months (2-4 infusions) according to disease activity, B-cell depletion, and IgG levels. The dynamics of clinical and laboratory data, the activity of the disease by SLEDAI, and corticosteroid doses were assessed at the onset and during the rituximab trial.
The main patient's characteristics were: Pre-rituximab non-biologic conventional treatment included: cyclophosphamide 15 (60%), MMF 8 (32%), azathioprine 3 (12%), hydroxychloroquine 12 (48%), and pulse therapy of methylprednisolone followed by oral methylprednisolone 25 (100%). The time before rituximab was 7.0 (3.0-24.0) months, and the whole observation period was 7.0 (0; 24) months. The initial pre-rituximab treatment slightly reduced SLEDAI levels and the proportion of patients with LN. A significant reduction of SLEDAI, the anti-dsDNA level, proteinuria, hematuria, C4 complement, ESR, and the median corticosteroid dose by 80% from the initial value, as well as the proportion of patients without corticosteroids, was observed after rituximab administration. Two deaths were observed due to catastrophic SLE with macrophage activation syndrome, accompanied by a severe infection (invasive aspergillosis, = 2). Three patients developed serious adverse events: pneumonia ( = 2), transient agranulocytosis ( = 1) after the third rituximab infusion, and meningitis, caused by Listeria monocytosis, after the first rituximab infusion. Eight patients received antibacterial treatment for different respiratory infections without hospital admissions.
Rituximab biosimilar BCD020 showed effectiveness in LN, whereas previous non-biologic treatment was insufficiently effective. Randomized controlled trials are required to evaluate the efficacy and safety of rituximab and evaluate the benefits when compared with conventional SLE treatment.
儿童狼疮性肾炎（LN）是系统性红斑狼疮（SLE）在儿童中最严重的表现之一，决定着疾病的预后。儿童LN尚无标准化治疗方案，生物制剂的作用尚未最终明确。
分析利妥昔单抗生物类似药BCD020在儿童狼疮性肾炎患者中的安全性和有效性。
在一项回顾性队列研究中，纳入了25例LN患者（10例男孩和15例女孩）的病历数据，发病年龄为13（9 - 16）岁，这些患者常规非生物治疗失败或出现皮质类固醇依赖/毒性反应。诊断采用系统性红斑狼疮国际协作临床（SLICC）分类标准。根据疾病活动度、B细胞清除情况和IgG水平，利妥昔单抗生物类似药BCD020的给药剂量为375 mg/m² 每周（2 - 4次输注），每6 - 12个月重复疗程（2 - 4次输注）。在开始使用利妥昔单抗治疗时及治疗期间评估临床和实验室数据的动态变化、SLEDAI评估的疾病活动度以及皮质类固醇剂量。
患者的主要特征如下：利妥昔单抗治疗前的非生物常规治疗包括：环磷酰胺15例（60%）、霉酚酸酯8例（32%）、硫唑嘌呤3例（12%）、羟氯喹12例（48%），以及甲泼尼龙冲击治疗后口服甲泼尼龙25例（100%）。使用利妥昔单抗前的时间为7.0（3.0 - 24.0）个月，整个观察期为7.0（0；24）个月。利妥昔单抗治疗前的初始治疗使SLEDAI水平和LN患者比例略有降低。使用利妥昔单抗后，SLEDAI、抗双链DNA水平、蛋白尿、血尿、C4补体、血沉以及皮质类固醇中位剂量较初始值显著降低80%，且无皮质类固醇治疗的患者比例增加。观察到2例因伴有巨噬细胞活化综合征的灾难性SLE死亡，伴有严重感染（侵袭性曲霉病，n = 2）。3例患者发生严重不良事件：第三次利妥昔单抗输注后出现肺炎（n = 2）、短暂性粒细胞缺乏症（n = 1），以及第一次利妥昔单抗输注后由单核细胞增生李斯特菌引起的脑膜炎。8例患者因不同的呼吸道感染接受抗菌治疗但未住院。
利妥昔单抗生物类似药BCD020在LN中显示出有效性，而之前的非生物治疗效果不佳。需要进行随机对照试验来评估利妥昔单抗的疗效和安全性，并与传统SLE治疗进行比较以评估其益处。
