探讨泰它西普(telitacicept)治疗儿童难治性IgA血管炎性肾炎(IgAVN)的临床疗效及安全性。

选择2024年8月1日至2025年3月1日在西安市儿童医院肾脏科住院并接受泰它西普治疗的4例难治性IgAVN患儿(患儿1~4)为研究对象。其中，男性患儿为1例(患儿2)，女性为3例(患儿1、3、4)。这4例患儿均在原有糖皮质激素和(或)免疫抑制剂及血管紧张素转换酶抑制剂(ACEI)/血管紧张素Ⅱ受体阻滞剂(ARB)类药物等常规治疗基础上加用泰它西普，根据患儿体重分层，对其采取80 mg/次或160 mg/次皮下注射，每周1次，治疗时间≥24周。采用回顾性分析方法分析4例患儿治疗前及治疗后24 h尿蛋白定量、尿蛋白/尿肌酐比值(UPCR)、尿常规结果，以及血清白蛋白、估算肾小球滤过率(eGFR)、血脂、血清免疫球蛋白(Ig)水平及B淋巴细胞计数等指标，并记录糖皮质激素及其他免疫抑制剂用量变化。以"IgA血管炎性肾炎""IgA vasculitis with nephritis""IgAVN""泰它西普""telitacicept"分别为中、英文关键词，于中国知网、万方数据知识服务平台、中华医学期刊全文数据库及PubMed数据库中，检索关于泰它西普治疗儿童IgAVN的相关研究文献。本次检索时间设定为2021年3月至2025年3月。本研究遵循的程序通过西安市儿童医院伦理委员会批准(审批文号：2025-019-01)，并且所有患儿监护人对诊治知情同意，并签署书面临床研究知情同意书。

①这4例患儿首次应用泰它西普治疗时的年龄为10岁9个月至16岁3个月。对其采用泰它西普治疗后随访24周时，患儿1、2、4的24 h尿蛋白定量，较基线(本研究以下所称的基线，均是指患儿1~4该指标采取泰它西普治疗前的水平)下降，UPCR变化趋势与24 h尿蛋白定量总体一致；患儿3蛋白尿指标波动较大，未见持续下降趋势。治疗期内，4例患儿的eGFR总体保持稳定，血清白蛋白水平均较基线升高，升高率为2.7%~12.7%；患儿1、2、4治疗前合并高胆固醇血症，治疗后血清总胆固醇水平均较基线下降，下降率为8.5%~43.1%，患儿3治疗前血清总胆固醇水平未见明显异常，治疗后变化不明显。治疗结束随访至24周时，4例患儿的血清IgG、IgM及IgA水平，均较基线不同程度下降，下降率分别为23.5%~45.5%、53.8%~83.4%及35.9%~56.0%，其中患儿1的血清IgM及IgA水平在24周时稍低于正常值，血清IgG处于正常水平；患儿2的血清IgG、IgM及IgA水平在24周时均低于正常值，但未降至低免疫球蛋白血症水平；患儿3的Ig水平均高于正常值；患儿4的IgG及IgM水平在24周时稍低于正常值，血清IgA处于正常水平；与采取泰它西普治疗前比较，B淋巴细胞计数总体较基线呈下降趋势。这4例患儿首次应用泰它西普治疗时，采取糖皮质激素治疗的中位剂量为0.29 mg/(kg·d)，末次随访时中位剂量降至0.215 mg/(kg·d)，较基线减少25.9%，其中患儿2于泰它西普治疗24周后，各项指标好转，并停用糖皮质激素。随访期内4例患儿均发生治疗相关感染不良反应，其中患儿1~ 3发生上呼吸道感染，患儿4发生胃肠道感染，经口服抗感染治疗药物及对症治疗后均缓解；未发生注射部位不良反应及其他严重不良事件。②文献复习结果显示，采用本研究设定的检索策略，共检索到5篇关于泰它西普治疗儿童IgAVN的相关文献，纳入患儿为24例(患儿5~28)，加上本研究患儿1~4，共计28例(患儿1~28)纳入进行泰它西普治疗难治性IgAVN疗效及安全性综合分析。对这28例患儿均采取泰它西普皮下注射治疗，每周1次。治疗后，其中17例患儿24 h尿蛋白定量降至正常范围；7例采取泰它西普治疗前存在肉眼血尿者肉眼血尿改善，21例镜下血尿者不同程度减轻；16例Ig水平下降，以IgG下降较为常见。泰它西普治疗难治性IgAVN患儿的安全性方面，未见严重不良事件或因不良反应停用泰它西普者，主要不良反应包括上呼吸道感染、胃肠道感染及低免疫球蛋白血症。

泰它西普可改善难治性IgAVN患儿蛋白尿水平，并有助于糖皮质激素减量，短期安全性较好，但是其长期疗效及安全性，仍需多中心、大样本、长期随访的前瞻性对照研究进一步证实。

To evaluate the efficacy and safety of telitacicept in children with refractory IgA vasculitis with nephritis(IgAVN).

Four children with refractory IgAVN who were hospitalized and treated with telitacicept in the Department of Nephrology, Xi′an Children′s Hospital from August 1, 2024 to March 1, 2025 were enrolled, including 1 boy (case 2) and 3 girls (cases 1, 3, and 4). All 4 children received telitacicept as add-on therapy on the basis of conventional treatment with glucocorticoids and/or immunosuppressants, as well as angiotensin-converting enzyme inhibitors or angiotensin Ⅱ receptor blockers. Telitacicept was administered by subcutaneous injection once weekly at a weight-based dose of 80 mg or 160 mg per dose, with a treatment duration of no less than 24 weeks. Clinical data before and after treatment were retrospectively analyzed, including 24-hour urinary protein excretion, urine protein-to-creatinine ratio (UPCR), routine urinalysis, serum albumin, estimated glomerular filtration rate (eGFR), blood lipid levels, immunoglobulin levels, and B lymphocyte counts. Changes in the doses of glucocorticoids and other immunosuppressants were also recorded. China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, Chinese Medical Journal Full-text Database, and PubMed were searched using" IgAVN" " IgA vasculitis nephritis" and " telitacicept" as search keywords to identify studies on telitacicept in the treatment of pediatric IgAVN. The retrieval period was from March 2021 to March 2025. This study was approved by the Ethics Committee of Xi′an Children′s Hospital (Approval No. 2025-019-01), and written informed consent was obtained from the guardians of all children.

① Among these 4 cases, 1 was male (case 2) and 3 were female (cases 1, 3, and 4). The age at first administration of telitacicept ranged from 10 years and 9 months to 16 years and 3 months. At 24 weeks of follow-up, 24-hour urinary protein excretion decreased from baseline in cases 1, 2, and 4, and the changing trend of urine protein-to-creatinine ratio (UPCR) was generally consistent with that of 24-hour urinary protein excretion. In case 3, proteinuria-related indicators fluctuated markedly, without a sustained decreasing trend. During treatment, estimated glomerular filtration rate (eGFR) remained generally stable in all 4 cases, and serum albumin levels increased from baseline, with an increase ranging from 2.7% to 12.7%. Cases 1, 2, and 4 had hypercholesterolemia before treatment, and their serum total cholesterol levels decreased from baseline after treatment, with a decrease ranging from 8.5% to 43.1%. Case 3 had no obvious abnormality in serum total cholesterol level before treatment, and no obvious change was observed after treatment. At 24 weeks of treatment, serum IgG, IgM, and IgA levels decreased to varying degrees from baseline in all 4 cases, with decreases of 23.5%-45.5%, 53.8%-83.4%, and 35.9%-56.0%, respectively. B lymphocyte counts showed an overall decreasing trend. The median glucocorticoid dose at first administration of telitacicept was 0.29 mg/(kg·d), which decreased to 0.215 mg/(kg·d) at the last follow-up, representing a 25.9% reduction from baseline. Case 2 discontinued glucocorticoids after 24 weeks of treatment. During follow-up, all 4 cases developed infectious events. Cases 1-3 developed upper respiratory tract infections, and case 4 developed gastrointestinal infection. All infections resolved after oral medication and symptomatic treatment. No injection-site reactions or serious adverse events were observed. ② The literature review identified 5 relevant studies involving 24 children. Together with the 4 cases in this study, a total of 28 children were included in the summary analysis. All 28 children received subcutaneous telitacicept once weekly. Among them, 17 children had 24-hour urinary protein excretion reduced to the normal range, gross hematuria improved after treatment in 7 children who had gross hematuria before treatment, and microscopic hematuria was alleviated to varying degrees in 21 children. Immunoglobulin levels decreased after treatment in 16 children, with IgG reduction being the most common. In terms of safety, no serious adverse events or discontinuation of telitacicept due to adverse reactions were reported. The main adverse reactions included upper respiratory tract infection, gastrointestinal infection, and hypogammaglobulinemia.

Telitacicept can improve proteinuria and reduce glucocorticoid dosage in children with refractory IgAVN, with no serious adverse events were observed during short-term follow-up. However, its long-term efficacy and safety need to be further confirmed by large-sample studies with long-term follow-up.