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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.
BACKGROUND: NCT04074187.
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.
BACKGROUND: NCT04074187.
摘要：
背景：最近一项针对日本患者的2/3期研究表明，卡普拉斯单抗可有效治疗免疫介导的血栓性血小板减少性紫癜（iTTP），iTTP复发率低。在caplacizumab治疗期间每周监测ADAMTS13活性以指导停止caplacizumab并因此避免恶化或复发。这项研究的目的是评估该患者人群在卡普拉斯珠单抗治疗期间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iTTP的≥18岁的患者在TPE后30天每天接受10mgcaplacizumab联合治疗性血浆置换（TPE）和免疫抑制。结果包括恢复ADAMTS13活性的时间，治疗结束时的ADAMTS13活性水平，ADAMTS13抑制剂再升高的发生率(即，抑制剂增强)在治疗期间，血小板计数恢复的时间，TPE的天数，和安全。还评估了根据抑制剂加强的存在的结果。
结果：19例患者证实iTTP并纳入本分析。ADAMTS13活性恢复至≥10%的中位数（95%置信区间）时间，≥20%,≥60%为14.6（5.9-24.8），18.5（5.9-31.8），和47.5（18.5-60.9）天，分别。在caplacizumab治疗结束时,ADAMTS13活性水平的中位数(范围)为62.0%(29.0-101.0)。9例患者有ADAMTS13抑制剂增强。在抑制剂增强的患者中观察到ADAMTS13活性的延迟反应。与不使用抑制剂的患者相比，使用抑制剂的患者的血小板计数反应的中位时间和TPE天数的中位时间更短。利妥昔单抗用于几乎所有使用抑制剂加强的患者（88.9％），完成TPE后。用利妥昔单抗治疗的无抑制剂增强的患者在TPE完成之前接受了它。只有一个病人经历了复发,在因不良事件而停用caplacizumab后不久发生.
结论：在iTTP患者中，如果利妥昔单抗在iTTP治疗期早期给药,卡普拉斯单抗联合TPE和免疫抑制可能会降低ADAMTS13抑制剂增强的风险.除卡普拉斯单抗外，早期服用利妥昔单抗可以预防iTTP复发，并增强抑制剂。
背景：NCT04074187。
方法：对日本患者的2/3期研究进行事后分析。确诊iTTP的≥18岁的患者在TPE后30天每天接受10mgcaplacizumab联合治疗性血浆置换（TPE）和免疫抑制。结果包括恢复ADAMTS13活性的时间，治疗结束时的ADAMTS13活性水平，ADAMTS13抑制剂再升高的发生率(即，抑制剂增强)在治疗期间，血小板计数恢复的时间，TPE的天数，和安全。还评估了根据抑制剂加强的存在的结果。
结果：19例患者证实iTTP并纳入本分析。ADAMTS13活性恢复至≥10%的中位数（95%置信区间）时间，≥20%,≥60%为14.6（5.9-24.8），18.5（5.9-31.8），和47.5（18.5-60.9）天，分别。在caplacizumab治疗结束时,ADAMTS13活性水平的中位数(范围)为62.0%(29.0-101.0)。9例患者有ADAMTS13抑制剂增强。在抑制剂增强的患者中观察到ADAMTS13活性的延迟反应。与不使用抑制剂的患者相比，使用抑制剂的患者的血小板计数反应的中位时间和TPE天数的中位时间更短。利妥昔单抗用于几乎所有使用抑制剂加强的患者（88.9％），完成TPE后。用利妥昔单抗治疗的无抑制剂增强的患者在TPE完成之前接受了它。只有一个病人经历了复发,在因不良事件而停用caplacizumab后不久发生.
结论：在iTTP患者中，如果利妥昔单抗在iTTP治疗期早期给药,卡普拉斯单抗联合TPE和免疫抑制可能会降低ADAMTS13抑制剂增强的风险.除卡普拉斯单抗外，早期服用利妥昔单抗可以预防iTTP复发，并增强抑制剂。
背景：NCT04074187。
