Caplacizumab prevents refractoriness and mortality in acquired thrombotic thrombocytopenic purpura: integrated analysis
Caplacizumab prevents refractoriness and mortality in acquired thrombotic thrombocytopenic purpura: integrated analysis
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DOI：
10.1182/bloodadvances.2020001834
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发表时间：
2021-04-22
期刊：
影响因子：
7.5
通讯作者：
Callewaert, Filip
中科院分区：
文献类型：
--
作者：
Peyvandi, Flora;Cataland, Spero;Callewaert, Filip
已在II期TITAN和III期HERCULES试验中确定caplacizumab在获得性血栓性血小板减少性紫癜（aTTP）患者中的疗效和安全性。对两项试验的数据进行了综合分析，以增加评估疗效和安全性结局治疗差异的统计学把握度。与安慰剂相比，Caplacizumab治疗期间死亡人数显著减少（0 vs 4; P < .05），难治性TTP发生率显著降低（0 vs 8; P < .05）。与个体试验一致，caplacizumab治疗导致血小板计数应答时间更快（风险比，1.65; P <0.001），在治疗期间，具有TTP相关死亡、RIP恶化或发生至少1起治疗后出现的重大血栓栓塞事件的复合终点的患者比例降低72.6%（13.0%对47.3%; P <0.001），治疗性血浆置换天数中位数（5.0对7.5天）比安慰剂减少33.3%。未发现新的安全性信号;轻度皮肤粘膜出血是主要安全性结果。这项综合分析提供了新的证据，证明caplacizumab可预防获得性UP患者的死亡率和难治性疾病，并强化了个体试验结果，证实了良好的安全性和耐受性特征。这些试验在www.clinicaltrials.gov上注册为#NCT 01151423和#NCT 02553317。
The efficacy and safety of caplacizumab in individuals with acquired thrombotic thrombocytopenic purpura (aTTP) have been established in the phase 2 TITAN and phase 3 HERCULES trials. Integrated analysis of data from both trials was conducted to increase statistical power for assessing treatment differences in efficacy and safety outcomes. Caplacizumab was associated with a significant reduction in the number of deaths (0 vs 4; P < .05) and a significantly lower incidence of refractory TTP (0 vs 8; P < .05) vs placebo during the treatment period. Consistent with the individual trials, treatment with caplacizumab resulted in a faster time to platelet count response (hazard ratio, 1.65; P < .001), a 72.6% reduction in the proportion of patients with the composite end point of TTP-related death, rip exacerbation, or occurrence of at least 1 treatment-emergent major thromboembolic event during the treatment period (13.0% vs 47.3%; P < .001), and a 33.3% reduction in the median number of therapeutic plasma exchange days (5.0 vs 7.5 days) vs placebo. No new safety signals were identified; mild mucocutaneous bleeding was the main safety finding. This integrated analysis provided new evidence that caplacizumab prevents mortality and refractory disease in acquired UP and strengthened individual trial findings, with a confirmed favorable safety and tolerability profile. These trials were registered at www.clinicaltrials.gov as #NCT01151423 and #NCT02553317.