Cugno Massimo, Capone Valentina, Griffini Samantha, Grovetti Elena, Pintarelli Giulia, Porcaro Luigi, Clementi Emilio, Ardissino Gianluigi
Medicina Interna, Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Università Degli Studi di Milano, Via Pace, 9, 20122, Milano, Italy.
Center for HUS Prevention, Control and Management at Pediatric Nephrology, Dialysis and Transplant Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milano, Italy.
J Nephrol. 2022 May;35(4):1205-1211. doi: 10.1007/s40620-021-01187-8. Epub 2022 Jan 11.
Atypical hemolytic uremic syndrome (aHUS) is characterized by platelet consumption, hemolysis, and renal injury. Eculizumab, a humanized antibody that blocks complement activity, has been successfully used in aHUS, but the best treatment schedule has not yet been clearly defined.
Herein we report our experience with eculizumab maintenance treatment, in which the interval between subsequent doses was adjusted based on classical complement pathway (CCP) activity, targeted to < 30% for the prevention of relapses. Trough circulating levels of free eculizumab were determined by an immunoenzymatic method. Genetic and serologic characteristics of the patients were also assessed.
We report on 38 patients with aHUS with a median age of 25.0 years (range 0.5-60.0 years) treated with eculizumab. Once stable disease remission was obtained, the interval between eculizumab doses was extended based on target CCP activity. With this approach, presently, 22 patients regularly receive eculizumab infusion every 28 days and 16 receive it every 21. During a median observation period of 32.3 months (range 4.0-92.4 months) and a cumulative period of 1295 months, no patient relapsed. An inverse correlation between CCP activity and eculizumab circulating levels was present (r = - 0.690, p = 0.0001), with CCP activity being inhibited as long as free eculizumab was measurable in serum.
In patients with aHUS on eculizumab maintenance treatment, complement activity measurement can be used as a proxy for circulating levels of the drug. Monitoring complement activity allows for safe tailoring of the frequency of eculizumab administration, thus avoiding excessive drug exposure while keeping the disease in remission.
非典型溶血尿毒综合征（aHUS）的特征是血小板消耗、溶血和肾损伤。依库珠单抗是一种阻断补体活性的人源化抗体，已成功用于aHUS的治疗，但最佳治疗方案尚未明确界定。
在此，我们报告依库珠单抗维持治疗的经验，其中后续剂量之间的间隔根据经典补体途径（CCP）活性进行调整，目标是<30%以预防复发。采用免疫酶法测定游离依库珠单抗的谷循环水平。还评估了患者的基因和血清学特征。
我们报告了38例接受依库珠单抗治疗的aHUS患者，中位年龄为25.0岁（范围0.5 - 60.0岁）。一旦获得稳定的疾病缓解，依库珠单抗剂量之间的间隔根据目标CCP活性延长。采用这种方法，目前，22例患者每28天定期接受依库珠单抗输注，16例患者每21天接受一次。在中位观察期32.3个月（范围4.0 - 92.4个月）和累积1295个月期间，无患者复发。CCP活性与依库珠单抗循环水平之间存在负相关（r = - 0.690，p = 0.0001），只要血清中可检测到游离依库珠单抗，CCP活性就会受到抑制。
在接受依库珠单抗维持治疗的aHUS患者中，补体活性测量可作为药物循环水平的替代指标。监测补体活性有助于安全调整依库珠单抗给药频率，从而避免药物过度暴露，同时使疾病保持缓解状态。
