The burden of illness of patients with paroxysmal nocturnal haemoglobinuria receiving C5 inhibitors: clinical outcomes and medical encounters from the patient perspective

To assess the clinical and healthcare resource burden among C5 inhibitor (C5i)-treated patients with paroxysmal nocturnal haemoglobinuria (PNH), using patient-reported data. This web-based, cross-sectional survey (01FEB2021–31MAR2021) of adults with PNH treated with eculizumab (France, Germany, UK) or ravulizumab (Germany) included: patient characteristics; treatment patterns/dosage; haematological outcomes (haemoglobin [Hb] levels, transfusions, thrombotic events, breakthrough haemolysis); and medical encounters. Treatment and Hb-level subgroup differences were assessed with statistical significance tests. Among 71 patients, 98.6% were C5i-treated for ≥3 months. The majority (with reported Hb levels) had levels ≤12.0 g/dL (85.7%; <i>n</i> = 54/63). The mean Hb level was 10.2 g/dL (standard deviation [SD]: 2.0; median 10.0 g/dL). Treatment with above label-recommended doses was reported by 30.4% (eculizumab) and 5.3% (ravulizumab) of patients. Within the past 12 months among patients treated with C5i for ≥1 year: 24.1% had ≥1 transfusion; 3.2% had ≥1 thrombosis; and 28.6% had ≥1 breakthrough haemolysis. Among all patients, 26.8% and 31.0% reported emergency department/room [ER] and inpatient visits, respectively. Mean annual, per-patient all-cause medical encounters were: 0.5 (ER); 1.9 (inpatient); and overall outpatient visits ranged by setting from 2.0 to 6.4. Most encounters were PNH-related, with means of 0.4 (ER); 1.8 (inpatient); and 1.6–5.4 (outpatient). Primary haematological and medical encounter outcomes were similar between treatment as well as Hb-level subgroups, with almost no statistically significant differences. Despite at least 3 months of C5i treatment, high proportions of patients with PNH reported low haemoglobin levels and required transfusions and hospitalizations, which suggests remaining unmet needs.

本研究利用患者报告的临床数据，评估接受C5抑制剂（C5 inhibitor，C5i）治疗的阵发性睡眠性血红蛋白尿症（paroxysmal nocturnal haemoglobinuria，PNH）患者的临床结局与医疗资源负担情况。本项基于网络的横断面调查（2021年2月1日—2021年3月31日）纳入了接受依库珠单抗（eculizumab，法国、德国、英国）或瑞武利单抗（ravulizumab，德国）治疗的PNH成年患者，调查内容包括患者基线特征、治疗模式与给药剂量、血液学结局（血红蛋白[Hb]水平、输血情况、血栓事件、突破性溶血）以及医疗就诊情况。研究通过统计学显著性检验评估了治疗方案与血红蛋白水平亚组间的差异。共纳入71例患者，其中98.6%接受C5i治疗时长≥3个月。在报告了血红蛋白水平的患者中，多数（85.7%，n=54/63）的血红蛋白水平≤12.0g/dL。受试者的平均血红蛋白水平为10.2g/dL（标准差[SD]：2.0；中位数10.0g/dL）。据报告，30.4%接受依库珠单抗治疗的患者、5.3%接受瑞武利单抗治疗的患者采用了超出药品说明书推荐剂量的给药方案。在接受C5i治疗≥1年的患者中，过去12个月内：24.1%至少接受过1次输血；3.2%至少发生过1次血栓事件；28.6%至少出现过1次突破性溶血。所有受试者中，分别有26.8%、31.0%报告过急诊室（emergency department/room，ER）就诊与住院治疗经历。每位患者的年全因医疗就诊次数均值为：急诊0.5次、住院1.9次；不同场景下的门诊就诊总次数区间为2.0~6.4次。多数就诊与PNH相关，相关就诊的均值为：急诊0.4次、住院1.8次、门诊1.6~5.4次。血液学与医疗就诊的主要结局在不同治疗方案亚组及不同血红蛋白水平亚组间均较为相似，几乎无统计学显著性差异。尽管接受了至少3个月的C5i治疗，仍有较高比例的PNH患者报告存在低血红蛋白水平、需要输血及住院治疗，这提示目前仍存在未被满足的临床需求。