Institute of Transfusion Medicine, University of Ulm, and Institute for Clinical Transfusion Medicine and Immunogenetics, German Red Cross Blood Transfusion Service Baden-Württemberg-Hessen and University Hospital Ulm, Ulm, Germany.
Hôpital Saint Louis, Paris, France.
Eur J Haematol. 2022 Sep;109(3):197-204. doi: 10.1111/ejh.13773. Epub 2022 Jun 21.
The effects of eculizumab treatment in paroxysmal nocturnal hemoglobinuria (PNH) patients with or without high-disease activity (HDA), defined by LDH ≥ 1.5 × ULN and history of major adverse vascular events (MAVEs; including thrombotic events [TEs]); anemia; and/or physician-reported abdominal pain, dyspnea, dysphagia, erectile dysfunction, fatigue, and/or hemoglobinuria, in the International PNH Registry were evaluated.
Registry patients were stratified by baseline HDA and eculizumab-treatment status. Longitudinal changes in laboratory and clinical PNH-related endpoints were evaluated using linear mixed models (continuous variables) or Poisson regression (incidence rates).
As of May 1, 2017, 3009 patients (HDA/eculizumab-treated, n = 913; HDA/never-treated, n = 651; no-HDA/eculizumab-treated, n = 173; no-HDA/never-treated, n = 1272) were analyzed. Higher proportions of eculizumab-treated patients had HDA and history of MAVEs. In patients with and without HDA, respectively, eculizumab treatment resulted in reductions from baseline for (1) LDH ratio (mean [SD]: -5.3 [4.0] and -2.3 [3.8]); (2) incidence rate ratio (IRR) for MAVEs (-80% and -70%); (3) IRR for TEs (-80% for both); and (4) units of red blood cell transfusions per year (from 6.8 to 2.8 and 3.6 to 2.5 units).
Eculizumab treatment in a real-world setting improved outcomes, including substantial decreases in hemolysis, MAVE rates, TEs, and transfusions in PNH patients regardless of HDA.
在国际阵发性睡眠性血红蛋白尿症(PNH)登记处,评估了依库珠单抗治疗伴有或不伴有高疾病活动度(HDA)的 PNH 患者的效果,HDA 的定义为乳酸脱氢酶(LDH)≥1.5×正常值上限(ULN),且有重大血管不良事件(MAVE;包括血栓形成事件[TEs])、贫血和/或医生报告的腹痛、呼吸困难、吞咽困难、勃起功能障碍、疲劳和/或血红蛋白尿的病史。
根据基线 HDA 和依库珠单抗治疗情况对登记处患者进行分层。使用线性混合模型(连续变量)或泊松回归(发病率)评估实验室和临床 PNH 相关终点的纵向变化。
截至 2017 年 5 月 1 日,共分析了 3009 例患者(HDA/依库珠单抗治疗,n=913;HDA/从未治疗,n=651;无 HDA/依库珠单抗治疗,n=173;无 HDA/从未治疗,n=1272)。接受依库珠单抗治疗的患者中 HDA 和 MAVE 病史的比例更高。在有和没有 HDA 的患者中,依库珠单抗治疗分别导致以下指标从基线下降:(1)LDH 比值(平均值[标准差]:-5.3[4.0]和-2.3[3.8]);(2)MAVE 发病率比(IRR)(-80%和-70%);(3)TE 的 IRR(-80%,两者相同);和(4)每年红细胞输注单位数(从 6.8 降至 2.8 和 3.6 降至 2.5 单位)。
在真实世界环境中,依库珠单抗治疗改善了结局,包括无论 HDA 情况如何,PNH 患者的溶血、MAVE 发生率、TEs 和输血均显著减少。