Safety of Repeated Open-Label Treatment Courses of Intravenous Ofatumumab, a Human Anti-CD20 Monoclonal Antibody, in Rheumatoid Arthritis: Results from Three Clinical Trials.
Safety of Repeated Open-Label Treatment Courses of Intravenous Ofatumumab, a Human Anti-CD20 Monoclonal Antibody, in Rheumatoid Arthritis: Results from Three Clinical Trials.
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类风湿关节炎中静脉注射术的重复开放标签治疗课程，一种人类抗CD20单克隆抗体：三项临床试验的结果。
DOI：
10.1371/journal.pone.0157961
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Kurrasch R
中科院分区：
文献类型：
--
作者：
Quattrocchi E;Østergaard M;Taylor PC;van Vollenhoven RF;Chu M;Mallett S;Perry H;Kurrasch R
探讨奥法木单抗再治疗类风湿关节炎的安全性。参加两项 III 期试验（OFA110635 和 OFA110634）和一项 II 期扩展试验（OFA111752）的活动性类风湿关节炎患者在第一个疗程后 ≥24 周和进一步疗程后 ≥16 周接受个体化开放标签奥法木单抗再治疗（700 mg X 2 次静脉输注，间隔两周）。重新治疗需要临床反应的证据，然后疾病复发。这些研究被申办者提前终止，以重新将开发重点放在皮下给药上。由于研究设计和人群的差异，每项研究的数据均单独汇总。 483 例患者（OFA110635、OFA110634 和 OFA111752 中分别为 243、148 和 92 例）接受了最多 7 个静脉奥法木单抗治疗疗程；累积暴露时间分别为 463、182 和 175 患者年。课程之间的平均时间为 17-47 周。奥法木单抗引起外周 B 淋巴细胞的严重消耗。接受治疗的患者因 DAS28 的改善而获益。报告不良事件的比例为 93% (226/243)、91% (134/148) 和 76% (70/92)，严重不良事件的比例为 18% (44/243)、20% (30/148) 和 12% (11/92)，严重感染的比例为 3% (8/243)、5% (7/148) 和 1% (1/92) 的患者 分别为 OFA110635、OFA110634 和 OFA111752。最常见的不良事件是第一个疗程的第一次输注期间的输注相关反应（48-79%）；严重的输液相关反应很少见（<1% [1/243]、5% [8/148] 和 1% [1/92] 的患者）。发生两例死亡（暴发性乙型肝炎病毒感染和间质性肺疾病）。奥法木单抗通常耐受性良好，没有证据表明多次治疗会增加安全风险。严重感染并不常见，并且不会随着时间的推移而增加。临床试验.gov 110635 临床试验.gov 110634 临床试验.gov 111752
To investigate the safety of ofatumumab retreatment in rheumatoid arthritis. Patients with active rheumatoid arthritis participating in two phase III trials (OFA110635 and OFA110634) and a phase II extension trial (OFA111752) received individualised open-label ofatumumab retreatment (700 mg X 2 intravenous infusions two weeks apart) ≥24 weeks following the first course and ≥16 weeks following further courses. Retreatment required evidence of clinical response followed by disease relapse. These studies were prematurely terminated by the sponsor to refocus development on subcutaneous delivery. Due to differences in study designs and populations, data are summarised separately for each study. 483 patients (243, 148 and 92 in OFA110635, OFA110634 and OFA111752 respectively) received up to 7 treatment courses of intravenous ofatumumab; cumulative duration of exposure was 463, 182 and 175 patient-years, respectively. Mean time between courses was 17–47 weeks. Ofatumumab induced a profound depletion of peripheral B-lymphocytes. Retreated patients derived benefit based on improvement in DAS28. Adverse events were reported for 93% (226/243), 91% (134/148) and 76% (70/92), serious adverse events for 18% (44/243), 20% (30/148) and 12% (11/92) and serious infections for 3% (8/243), 5% (7/148) and 1% (1/92) of patients in OFA110635, OFA110634 and OFA111752, respectively. The most common adverse events were infusion-related reactions during the first infusion of the first course (48–79%); serious infusion-related reactions were rare (<1% [1/243], 5% [8/148], and 1% [1/92] of patients). Two deaths occurred (fulminant hepatitis B virus infection and interstitial lung disease). Ofatumumab was generally well tolerated with no evidence of increased safety risks with multiple retreatments. Serious infections were uncommon and did not increase over time. ClinicalTrials.gov 110635 ClinicalTrials.gov 110634 ClinicalTrials.gov 111752