PDF(Pubmed)
Abstract：
BACKGROUND: Although complement component 5 inhibitors (C5is) eculizumab and ravulizumab improve paroxysmal nocturnal hemoglobinuria (PNH) outcomes, patients may experience persistent anemia. This post hoc analysis investigated whether the complement component 3-targeted therapy pegcetacoplan also improved hematologic outcomes and reduced fatigue in patients with PNH and mild/moderate anemia.
METHODS: Patients with PNH and hemoglobin ≥10.0 g/dL at baseline of PADDOCK (N = 6), PRINCE (N = 8), and PEGASUS (N = 11) were included. Before receiving pegcetacoplan, PADDOCK and PRINCE patients were C5i-naive; PEGASUS patients had hemoglobin <10.5 g/dL despite stably dosed eculizumab. Hemoglobin concentrations, percentages of patients with concentrations ≥12 g/dL, and sex-specific normalization were assessed at baseline and after 16 weeks of pegcetacoplan, as were absolute reticulocyte counts (ARCs) and normalization and fatigue scores and normalization.
RESULTS: From baseline to week 16, mean (SD) hemoglobin concentrations increased in C5i-naive patients (PADDOCK: 10.5 [0.4] to 12.7 [1.1] g/dL; PRINCE: 11.3 [1.0] to 14.0 [1.3] g/dL) and those with suboptimal eculizumab responses (PEGASUS: 10.2 [0.2] to 12.8 [2.6] g/dL). Percentage of patients with hemoglobin ≥12 g/dL increased (PADDOCK: 0 to 60.0% [3 of 5 patients]; PRINCE: 25.0% [2 of 8] to 87.5% [7 of 8]; PEGASUS: 0 to 72.7% [8 of 11]). Sex-specific hemoglobin normalization at week 16 occurred in 40.0% (2 of 5) (PADDOCK), 62.5% (5 of 8) (PRINCE), and 63.6% (7 of 11) (PEGASUS). In all studies, mean ARCs decreased from above normal to normal and ARC normalization increased. Mean Functional Assessment of Chronic Illness Therapy-Fatigue scores improved from below to above or near normal. Two patients had serious adverse events (PEGASUS: post-surgery sepsis, breakthrough hemolysis); breakthrough hemolysis resolved without study discontinuation.
CONCLUSIONS: Patients with PNH and mild/moderate anemia who were C5i-naive or who had suboptimal hemoglobin concentrations despite eculizumab treatment had improved hematologic outcomes and reduced fatigue after initiating or switching to pegcetacoplan.
BACKGROUND: Trial registration numbers: PADDOCK (NCT02588833), PRINCE (NCT04085601; EudraCT, 2018-004220-11), PEGASUS (NCT03500549).
METHODS: Patients with PNH and hemoglobin ≥10.0 g/dL at baseline of PADDOCK (N = 6), PRINCE (N = 8), and PEGASUS (N = 11) were included. Before receiving pegcetacoplan, PADDOCK and PRINCE patients were C5i-naive; PEGASUS patients had hemoglobin <10.5 g/dL despite stably dosed eculizumab. Hemoglobin concentrations, percentages of patients with concentrations ≥12 g/dL, and sex-specific normalization were assessed at baseline and after 16 weeks of pegcetacoplan, as were absolute reticulocyte counts (ARCs) and normalization and fatigue scores and normalization.
RESULTS: From baseline to week 16, mean (SD) hemoglobin concentrations increased in C5i-naive patients (PADDOCK: 10.5 [0.4] to 12.7 [1.1] g/dL; PRINCE: 11.3 [1.0] to 14.0 [1.3] g/dL) and those with suboptimal eculizumab responses (PEGASUS: 10.2 [0.2] to 12.8 [2.6] g/dL). Percentage of patients with hemoglobin ≥12 g/dL increased (PADDOCK: 0 to 60.0% [3 of 5 patients]; PRINCE: 25.0% [2 of 8] to 87.5% [7 of 8]; PEGASUS: 0 to 72.7% [8 of 11]). Sex-specific hemoglobin normalization at week 16 occurred in 40.0% (2 of 5) (PADDOCK), 62.5% (5 of 8) (PRINCE), and 63.6% (7 of 11) (PEGASUS). In all studies, mean ARCs decreased from above normal to normal and ARC normalization increased. Mean Functional Assessment of Chronic Illness Therapy-Fatigue scores improved from below to above or near normal. Two patients had serious adverse events (PEGASUS: post-surgery sepsis, breakthrough hemolysis); breakthrough hemolysis resolved without study discontinuation.
CONCLUSIONS: Patients with PNH and mild/moderate anemia who were C5i-naive or who had suboptimal hemoglobin concentrations despite eculizumab treatment had improved hematologic outcomes and reduced fatigue after initiating or switching to pegcetacoplan.
BACKGROUND: Trial registration numbers: PADDOCK (NCT02588833), PRINCE (NCT04085601; EudraCT, 2018-004220-11), PEGASUS (NCT03500549).
摘要：
背景：尽管补体成分5抑制剂（C5is）依库珠单抗和雷武利珠单抗可改善阵发性夜间血红蛋白尿症（PNH）的结局，患者可能会出现持续性贫血。这项事后分析研究了补体成分3靶向治疗pegcetacoplan是否也改善了PNH和轻度/中度贫血患者的血液学结果并减少了疲劳。
方法：在PADDOCK基线时PNH和血红蛋白≥10.0g/dL的患者（N=6），王子（N=8），包括PEGASUS（N=11）。在收到pegcetacoplan之前，PADDOCK和PRINCE患者未接受C5i治疗；PEGASUS患者的血红蛋白<10.5g/dL，尽管依库珠单抗剂量稳定。血红蛋白浓度,浓度≥12g/dL的患者百分比，在基线和pegcetacoplan16周后评估性别特异性正常化，网织红细胞绝对计数(ARCs)和正常化以及疲劳评分和正常化.
结果：从基线到第16周，未接受C5i治疗的患者的平均（SD）血红蛋白浓度增加（PADDOCK：10.5[0.4]至12.7[1.1]g/dL；PRINCE：11.3[1.0]至14.0[1.3]g/dL）和具有次优依库珠单抗反应的患者（PEGASUS：10.2[0.2]至12.8血红蛋白≥12g/dL的患者百分比增加（PADDOCK：0至60.0％[5例患者中的3例];PRINCE：25.0％[2/8]至87.5％[7/8];PEGASUS：0至72.7％[8/11]）。第16周时性别特异性血红蛋白正常化的发生率为40.0％（5个中的2个）（PADDOCK），62.5%（5/8）（王子），和63.6%（11个中的7个）（PEGASUS）。在所有研究中,平均ARCs从高于正常下降到正常，ARC正常化增加。慢性病治疗的平均功能评估-疲劳评分从低到高于或接近正常。两名患者出现严重不良事件（PEGASUS：术后败血症，突破性溶血）；突破性溶血在没有停止研究的情况下解决。
结论：患有PNH和轻度/中度贫血的C5i初治或尽管依库珠单抗治疗仍未达到最佳血红蛋白浓度的患者，在开始或改用pegcetacoplan后，血液学结果改善，疲劳减轻。
背景：试验注册号：PADDOCK（NCT02588833），王子(NCT04085601;EudraCT,2018-004220-11),PEGASUS（NCT03500549）。
方法：在PADDOCK基线时PNH和血红蛋白≥10.0g/dL的患者（N=6），王子（N=8），包括PEGASUS（N=11）。在收到pegcetacoplan之前，PADDOCK和PRINCE患者未接受C5i治疗；PEGASUS患者的血红蛋白<10.5g/dL，尽管依库珠单抗剂量稳定。血红蛋白浓度,浓度≥12g/dL的患者百分比，在基线和pegcetacoplan16周后评估性别特异性正常化，网织红细胞绝对计数(ARCs)和正常化以及疲劳评分和正常化.
结果：从基线到第16周，未接受C5i治疗的患者的平均（SD）血红蛋白浓度增加（PADDOCK：10.5[0.4]至12.7[1.1]g/dL；PRINCE：11.3[1.0]至14.0[1.3]g/dL）和具有次优依库珠单抗反应的患者（PEGASUS：10.2[0.2]至12.8血红蛋白≥12g/dL的患者百分比增加（PADDOCK：0至60.0％[5例患者中的3例];PRINCE：25.0％[2/8]至87.5％[7/8];PEGASUS：0至72.7％[8/11]）。第16周时性别特异性血红蛋白正常化的发生率为40.0％（5个中的2个）（PADDOCK），62.5%（5/8）（王子），和63.6%（11个中的7个）（PEGASUS）。在所有研究中,平均ARCs从高于正常下降到正常，ARC正常化增加。慢性病治疗的平均功能评估-疲劳评分从低到高于或接近正常。两名患者出现严重不良事件（PEGASUS：术后败血症，突破性溶血）；突破性溶血在没有停止研究的情况下解决。
结论：患有PNH和轻度/中度贫血的C5i初治或尽管依库珠单抗治疗仍未达到最佳血红蛋白浓度的患者，在开始或改用pegcetacoplan后，血液学结果改善，疲劳减轻。
背景：试验注册号：PADDOCK（NCT02588833），王子(NCT04085601;EudraCT,2018-004220-11),PEGASUS（NCT03500549）。
