在日本进行的一项2/3期研究的事后分析：利妥昔单抗的一线使用可能预防免疫性血小板减少性紫癜患者在接受卡泊西单抗治疗期间ADAMTS13抑制剂活性增强。

Frontline use of rituximab may prevent ADAMTS13 inhibitor boosting during caplacizumab treatment in patients with iTTP: post hoc analysis of a phase 2/3 study in Japan.

作者信息

Imada Kazunori, Miyakawa Yoshitaka, Ichikawa Satoshi, Uchiyama Hitoji, Ueda Yasunori, Hashimoto Yasuhiro, Nishimi Masashi, Tsukamoto Masako, Tahara Sayaka, Matsumoto Masanori

机构信息

Department of Hematology, Japanese Red Cross Osaka Hospital, Osaka, Japan.

Department of Hematology, Saitama Medical University Hospital, Saitama, Japan.

出版信息

Thromb J. 2024 Aug 2;22(1):72. doi: 10.1186/s12959-024-00642-3.

DOI:10.1186/s12959-024-00642-3

PMID:39095866

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11297770/

Abstract

BACKGROUND

A recent Phase 2/3 study in Japanese patients showed that caplacizumab was effective in treating immune-mediated thrombotic thrombocytopenic purpura (iTTP), with a low rate of iTTP recurrence. ADAMTS13 activity is monitored weekly during caplacizumab treatment to guide discontinuation of caplacizumab and consequently avoid exacerbations or relapse. The aim of this study was to assess changes in ADAMTS13 activity/inhibitor levels during caplacizumab treatment in this patient population.

METHODS

A post hoc analysis of the Phase 2/3 study in Japanese patients was conducted. Patients ≥ 18 years old with confirmed iTTP received 10 mg of caplacizumab daily in conjunction with therapeutic plasma exchange (TPE) and immunosuppression for 30 days post-TPE. Outcomes included time to recovery of ADAMTS13 activity, ADAMTS13 activity level at treatment end, incidence of ADAMTS13 inhibitor re-elevation (ie, inhibitor boosting) during treatment, time to platelet count recovery, number of days of TPE, and safety. Outcomes according to presence of inhibitor boosting were also assessed.

RESULTS

Nineteen patients had confirmed iTTP and were included in this analysis. Median (95% confidence interval) time to recovery of ADAMTS13 activity to ≥ 10%, ≥ 20%, and ≥ 60% was 14.6 (5.9-24.8), 18.5 (5.9-31.8), and 47.5 (18.5-60.9) days, respectively. Median (range) ADAMTS13 activity level at caplacizumab treatment end was 62.0% (29.0-101.0). Nine patients had ADAMTS13 inhibitor boosting. Delayed response of ADAMTS13 activity was observed in patients with inhibitor boosting. The median time to platelet count response and median number of TPE days were shorter in patients with inhibitor boosting compared with patients without inhibitor boosting. Rituximab was administered to almost all patients with inhibitor boosting (88.9%), after completion of TPE. Patients without inhibitor boosting who were treated with rituximab received it prior to completion of TPE. Only one patient experienced a recurrence, which occurred shortly after caplacizumab discontinuation due to an adverse event.

CONCLUSIONS

In patients with iTTP, caplacizumab with TPE and immunosuppression may reduce the risk of ADAMTS13 inhibitor boosting if rituximab is administered early in the iTTP treatment period. Early administration of rituximab in addition to caplacizumab may prevent iTTP recurrence with inhibitor boosting.

TRIAL REGISTRATION

NCT04074187.

摘要

背景

最近一项针对日本患者的2/3期研究表明，卡泊单抗在治疗免疫性血栓性血小板减少性紫癜（iTTP）方面有效，iTTP复发率较低。在卡泊单抗治疗期间，每周监测ADAMTS13活性，以指导停用卡泊单抗，从而避免病情加重或复发。本研究的目的是评估该患者群体在卡泊单抗治疗期间ADAMTS13活性/抑制剂水平的变化。

方法

对日本患者的2/3期研究进行事后分析。确诊为iTTP的≥18岁患者每天接受10 mg卡泊单抗治疗，并结合治疗性血浆置换（TPE）和免疫抑制治疗30天（TPE后）。观察指标包括ADAMTS13活性恢复时间、治疗结束时ADAMTS13活性水平、治疗期间ADAMTS13抑制剂再次升高（即抑制剂增强）的发生率、血小板计数恢复时间、TPE天数以及安全性。还评估了根据抑制剂增强情况的观察指标。

结果

19例患者确诊为iTTP并纳入本分析。ADAMTS13活性恢复至≥10%、≥20%和≥60%的中位（95%置信区间）时间分别为14.6（5.9 - 24.8）天、18.5（5.9 - 31.8）天和47.5（18.5 - 60.9）天。卡泊单抗治疗结束时ADAMTS13活性水平的中位（范围）为62.0%（29.0 - 101.0）。9例患者出现ADAMTS13抑制剂增强。在出现抑制剂增强的患者中观察到ADAMTS13活性的延迟反应。与未出现抑制剂增强的患者相比，出现抑制剂增强的患者血小板计数反应的中位时间和TPE天数的中位数较短。在几乎所有出现抑制剂增强的患者（88.9%）中，在TPE完成后给予了利妥昔单抗。未出现抑制剂增强且接受利妥昔单抗治疗的患者在TPE完成前接受了该药物。只有1例患者复发，发生在因不良事件停用卡泊单抗后不久。