Risitano Antonio M, de Castro Carlos, Han Bing, Kulasekararaj Austin, Maciejewski Jaroslaw P, Scheinberg Phillip, Ueda Yasutaka, Vallow Susan, Bermann Georgina, Dahlke Marion, Kumar Rakesh, Peffault de Latour Régis
Hematology and BMT Unit, AORN Moscati, Avellino, Italy.
Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy.
Blood Adv. 2025 Apr 22;9(8):1816-1826. doi: 10.1182/bloodadvances.2024014652.
Iptacopan, a first-in-class, oral, selective complement factor B inhibitor, demonstrated efficacy and safety as monotherapy in C5 inhibitor (C5i)-experienced (APPLY-PNH; NCT04558918) and C5i-naive (APPOINT-PNH; NCT04820530) patients with paroxysmal nocturnal hemoglobinuria (PNH). In the APPLY-PNH and APPOINT-PNH trials, changes in fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-Fatigue]) and health-related quality of life (HRQOL; European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ-C30]) from baseline to day 168 were evaluated. The proportion of patients achieving meaningful within-patient change (MWPC) on the FACIT-Fatigue and 4 EORTC QLQ-C30 subscales was evaluated using anchor-based thresholds, and correlations between FACIT-Fatigue scores, lactate dehydrogenase (LDH), and hemoglobin (Hb) levels were assessed. In APPLY-PNH (iptacopan, n = 62; C5i, n = 33), more patients in the iptacopan versus the C5i group reached the MWPC threshold for FACIT-Fatigue (51% vs 11%). More patients achieved MWPC on EORTC QLQ-C30 subscales in the iptacopan group (39%-49%) versus the C5i group (9%-20%). In APPOINT-PNH (N = 40), 56% achieved MWPC on the FACIT-Fatigue, and the proportion of patients who achieved MWPC on the EORTC QLQ-C30 ranged from 41% to 55%. In C5i-experienced patients, increased Hb levels correlated with improvement in FACIT-Fatigue scores (R = 0.48); in C5i-naive patients, increased Hb (R = 0.42) and decreased LDH (R = -0.53) (all P < .001) correlated with improved FACIT-Fatigue scores. C5i-experienced and -naive patients receiving iptacopan exhibited meaningful improvement in fatigue, HRQOL, and disease-related symptoms, which correlated with clinical improvement in hematologic markers of disease control.
依他库帕（Iptacopan）是一种一流的口服选择性补体因子B抑制剂，在阵发性夜间血红蛋白尿（PNH）患者中作为单药治疗，在既往接受过C5抑制剂（C5i）治疗的患者（APPLY-PNH研究；NCT04558918）和未接受过C5i治疗的患者（APPOINT-PNH研究；NCT04820530）中均显示出疗效和安全性。在APPLY-PNH和APPOINT-PNH试验中，评估了从基线到第168天疲劳（慢性病治疗功能评估-疲劳量表[FACIT-疲劳]）和健康相关生活质量（HRQOL；欧洲癌症研究与治疗组织生活质量问卷[EORTC QLQ-C30]）的变化。使用基于锚定的阈值评估了在FACIT-疲劳量表和EORTC QLQ-C30的4个分量表上实现有意义的患者内变化（MWPC）的患者比例，并评估了FACIT-疲劳评分、乳酸脱氢酶（LDH）和血红蛋白（Hb）水平之间的相关性。在APPLY-PNH研究中（依他库帕组，n = 62；C5i组，n = 33），与C5i组相比，依他库帕组有更多患者达到FACIT-疲劳量表的MWPC阈值（51%对11%）。依他库帕组在EORTC QLQ-C30分量表上实现MWPC的患者比例（39%-49%）高于C5i组（9%-20%）。在APPOINT-PNH研究中（N = 40），56%的患者在FACIT-疲劳量表上实现了MWPC，在EORTC QLQ-C30上实现MWPC的患者比例为41%至55%。在既往接受过C5i治疗的患者中，Hb水平升高与FACIT-疲劳评分改善相关（R = 0.48）；在未接受过C5i治疗的患者中，Hb升高（R = 0.42）和LDH降低（R = -0.53）（均P <.001）与FACIT-疲劳评分改善相关。接受依他库帕治疗的既往接受过C5i治疗和未接受过C5i治疗的患者在疲劳、HRQOL和疾病相关症状方面均有有意义的改善，这与疾病控制的血液学标志物的临床改善相关。
