Schrezenmeier Hubert, Kulasekararaj Austin, Mitchell Lindsay, Sicre de Fontbrune Flore, Devos Timothy, Okamoto Shinichiro, Wells Richard, Rottinghaus Scott T, Liu Peng, Ortiz Stephan, Lee Jong Wook, Socié Gérard
Institute of Transfusion Medicine, University of Ulm and Institute for Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service and University Hospital Ulm, Ulm, Germany.
Department of Haematological Medicine, King's College Hospital, NIHR/Wellcome King's Clinical Research Facility, London, UK.
Ther Adv Hematol. 2020 Oct 24;11:2040620720966137. doi: 10.1177/2040620720966137. eCollection 2020.
Ravulizumab, the only long-acting complement C5 inhibitor for adults with paroxysmal nocturnal hemoglobinuria (PNH), demonstrated non-inferiority to eculizumab after 26 weeks of treatment in complement inhibitor-naïve patients during a phase III randomized controlled trial. We present open-label extension results with up to 52 weeks of treatment.
Patients assigned to ravulizumab every 8 weeks (q8w) or eculizumab every 2 weeks during the randomized primary evaluation period received ravulizumab q8w during the 26-week extension. Efficacy endpoints were lactate dehydrogenase (LDH) normalization, transfusion avoidance, breakthrough hemolysis (BTH), LDH levels, Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale, and stabilized hemoglobin. Serum free C5 levels and safety were assessed. Outcomes as of the data cut-off (4 September 2018) were summarized using descriptive statistics.
Overall, 124 patients continued ravulizumab, and 119 switched from eculizumab to ravulizumab. During the extension, 43.5% and 40.3% of patients in the ravulizumab-ravulizumab and eculizumab-ravulizumab arms, respectively, achieved LDH normalization; 76.6% and 67.2% avoided transfusion. BTH decreased in the eculizumab-ravulizumab arm; no events were associated with free C5 ⩾0.5 μg/mL while receiving ravulizumab. Overall, 73.4% and 65.5% of patients in the ravulizumab-ravulizumab and eculizumab-ravulizumab arms, respectively, achieved stabilized hemoglobin. Similar proportions of patients achieved ⩾3-point improvement in FACIT-Fatigue at week 52 (ravulizumab-ravulizumab, 64.5%; eculizumab-ravulizumab, 57.1%). All patients maintained free C5 <0.5 μg/mL during the ravulizumab extension, including those who experienced C5 excursions ⩾0.5 μg/mL while receiving eculizumab during the primary evaluation period. Adverse events were comparable between groups and decreased over time.
In adult, complement inhibitor-naïve patients with PNH, ravulizumab q8w for up to 52 weeks demonstrated durable efficacy and was well tolerated, with complete and sustained free C5 inhibition and a decreased incidence of BTH with no events associated with loss of free C5 control.
ClinicalTrials.gov identifier, NCT02946463.
ravulizumab是唯一一种用于阵发性夜间血红蛋白尿（PNH）成人患者的长效补体C5抑制剂，在一项III期随机对照试验中，对于初治补体抑制剂的患者，治疗26周后，其疗效不劣于依库珠单抗。我们展示了长达52周治疗的开放标签扩展结果。
在随机化的主要评估期内每8周（q8w）接受ravulizumab或每2周接受依库珠单抗治疗的患者，在26周的扩展期内接受ravulizumab q8w治疗。疗效终点包括乳酸脱氢酶（LDH）正常化、避免输血、突破性溶血（BTH）、LDH水平、慢性病治疗功能评估（FACIT）-疲劳量表以及稳定血红蛋白水平。评估血清游离C5水平和安全性。使用描述性统计总结截至数据截止日期（2018年9月4日）的结果。
总体而言，124例患者继续接受ravulizumab治疗，119例从依库珠单抗转换为ravulizumab治疗。在扩展期，ravulizumab-ravulizumab组和依库珠单抗-ravulizumab组分别有43.5%和40.3%的患者实现LDH正常化；76.6%和67.2%的患者避免了输血。依库珠单抗-ravulizumab组的BTH有所减少；接受ravulizumab治疗期间，游离C5≥0.5μg/mL时未发生相关事件。总体而言，ravulizumab-ravulizumab组和依库珠单抗-ravulizumab组分别有73.4%和65.5%的患者实现了稳定血红蛋白水平。在第52周时，FACIT-疲劳量表改善≥3分的患者比例相似（ravulizumab-ravulizumab组为64.5%；依库珠单抗-ravulizumab组为57.1%）。在ravulizumab扩展期内，所有患者的游离C5均维持＜0.5μg/mL，包括在主要评估期接受依库珠单抗治疗时游离C5水平曾≥0.5μg/mL的患者。两组不良事件相当，且随时间减少。
在初治补体抑制剂的PNH成年患者中，长达52周的ravulizumab q8w治疗显示出持久疗效且耐受性良好，可实现完全且持续的游离C5抑制，BTH发生率降低，且未发生与游离C5控制丧失相关的事件。
ClinicalTrials.gov标识符，NCT02946463
