Mancuso Maria Cristina, Cugno Massimo, Griffini Samantha, Grovetti Elena, Nittoli Teresa, Mastrangelo Antonio, Tedesco Francesco, Montini Giovanni, Ardissino Gianluigi
Center for HUS Prevention, Control and Management at the Pediatric Nephrology, Dialysis and Transplantation Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Medicina Interna, Dipartimento Di Fisiopatologia Medico-Chirurgica E Dei Trapianti, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Università Degli Studi Di Milano, Milan, Italy.
Pediatr Nephrol. 2025 Jun;40(6):1959-1963. doi: 10.1007/s00467-025-06673-w. Epub 2025 Jan 22.
C3 glomerulopathy (C3G) is a rare kidney disease due to a dysregulation of the alternative complement pathway, orphan of specific treatment. Pegcetacoplan is an inhibitor of the third complement component C3, currently on a phase III registration protocol in C3G. Here we describe our experience with the off-label use of pegcetacoplan in pediatric patients with C3G.
This retrospective, observational study evaluated the efficacy and safety of pegcetacoplan in five pediatric patients, not eligible in the registration protocol, over a 12-week treatment period. The drug was given subcutaneously, twice a week for the first month, then weekly. The change in urinary protein-to-urinary creatinine ratio (mean of three samples) was the primary endpoint. We also evaluated the changes in serum C3, albumin, sC5-b9, creatinine, and urinary erythrocytes (number/µL).
At baseline, median proteinuria/creatininuria ratio (mean of three samples) was 4.97 mg/mg (3.53-7.69), and after 12 weeks of treatment with pegcetacoplan, it decreased to less than 30% of baseline (p = 0.043) as did erythrocyturia (p = 0.043). C3 levels increased more than 600% of baseline (p = 0.043), whereas the levels of sC5-b9 decreased to normal range (p = 0.043). Three of four patients with impaired kidney function showed an improvement in eGFR. No adverse event was recorded.
In C3G patients, pegcetacoplan therapy improves clinical and laboratory features during a 12-week treatment. The present study, although small and with a limited follow-up, supports the use of complement-targeted therapy in C3G. Further studies with a larger number of patients and longer follow-up are needed.
C3肾小球病（C3G）是一种由于替代补体途径失调导致的罕见肾病，缺乏特异性治疗方法。培克妥昔单抗是补体第三成分C3的抑制剂，目前正处于C3G的III期注册试验阶段。在此，我们描述了培克妥昔单抗在儿童C3G患者中进行非标签使用的经验。
这项回顾性观察研究评估了培克妥昔单抗在5名不符合注册试验标准的儿科患者中，为期12周的治疗期内的疗效和安全性。药物采用皮下注射，第一个月每周两次，之后每周一次。尿蛋白与尿肌酐比值（三个样本的平均值）的变化是主要终点。我们还评估了血清C3、白蛋白、sC5-b9、肌酐和尿红细胞（数量/微升）的变化。
基线时，蛋白尿/肌酐尿比值（三个样本的平均值）中位数为4.97mg/mg（3.53 - 7.69），培克妥昔单抗治疗12周后，该比值降至基线的30%以下（p = 0.043），血尿情况亦是如此（p = 0.043）。C3水平升高至基线的600%以上（p = 0.043），而sC5-b9水平降至正常范围（p = 0.043）。4名肾功能受损的患者中有3名的估算肾小球滤过率有所改善。未记录到不良事件。
在C3G患者中，培克妥昔单抗治疗在12周的治疗期内改善了临床和实验室指标。本研究虽然规模较小且随访有限，但支持在C3G中使用补体靶向治疗。需要开展更多患者数量和更长随访时间的进一步研究。
