Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by uncontrolled terminal complement activation leading to intravascular hemolysis (IVH), thrombosis, and impairments in quality of life (QoL). The aim of this study was to identify the clinical drivers of improvement in patient-reported outcomes (PROs) in patients with PNH receiving the complement component 5 (C5) inhibitors eculizumab and ravulizumab.

This post hoc analysis assessed clinical outcomes and PROs from 246 complement inhibitor-naive patients with PNH enrolled in a phase 3 randomized non-inferiority study that compared the C5 inhibitors ravulizumab and eculizumab (study 301; NCT02946463). The variables of interest were lactate dehydrogenase (LDH) levels, a surrogate measure of IVH, and hemoglobin (Hb) levels. PROs were collected using Functional Assessment of Chronic Illness Therapy—Fatigue (FACIT-F) and European Organisation for Research and Treatment of Cancer, Quality of Life Questionnaire—Core 30 (EORTC QLQ-C30) to assess fatigue and QoL, respectively.

Improvements in absolute mean LDH levels were significantly associated with improvements in mean FACIT-F score (p = 0.0024) and EORTC QLQ-C30 global health (GH) score (p < 0.0001) from baseline to day 183. Improvements in scores were achieved despite a non-significant increase in Hb levels. To understand the interaction between LDH and Hb, a regression analysis was performed: LDH response with Hb improvements was a significant predictor of improvement in fatigue. The independent effect of improved Hb did not significantly affect FACIT-F or EORTC QLQ-C30 GH scores.

These findings suggest that LDH levels are an important determinant of fatigue and QoL outcomes in patients with PNH. CTR: NCT02946463, October 27, 2016.

阵发性睡眠性血红蛋白尿 (PNH) 的特点是不受控制的终末补体激活，导致血管内溶血 (IVH)、血栓形成和生活质量 (QoL) 受损。本研究的目的是确定接受补体成分 5 (C5) 抑制剂依库珠单抗和拉维珠单抗的 PNH 患者改善患者报告结果 (PRO) 的临床驱动因素。

这项事后分析评估了 246 名未使用补体抑制剂的 PNH 患者的临床结果和 PRO，这些患者参加了一项 3 期随机非劣效性研究，该研究比较了 C5 抑制剂 ravulizumab 和 eculizumab（研究 301；NCT02946463）。感兴趣的变量是乳酸脱氢酶 (LDH) 水平（IVH 的替代指标）和血红蛋白 (Hb) 水平。使用慢性病治疗功能评估——疲劳 (FACIT-F) 和欧洲癌症研究和治疗组织生活质量问卷——核心 30 (EORTC QLQ-C30) 收集 PRO，分别评估疲劳和生活质量。

从基线到第 183 天，绝对平均 LDH 水平的改善与平均 FACIT-F 评分 ( p = 0.0024) 和 EORTC QLQ-C30 全球健康 (GH) 评分 ( p < 0.0001) 的改善显着相关。 Hb 水平无显着增加。为了了解 LDH 和 Hb 之间的相互作用，进行了回归分析：LDH 响应与 Hb 的改善是疲劳改善的重要预测因素。 Hb 改善的独立效应并未显着影响 FACIT-F 或 EORTC QLQ-C30 GH 评分。

这些发现表明，LDH 水平是 PNH 患者疲劳和生活质量结果的重要决定因素。点击率： NCT02946463，2016 年 10 月 27 日。