Department of Hematology and Oncology, University Hospital Regensburg, Regensburg, Germany.
Internal Medicine, Vivantes Clinic Friedrichshain, Berlin, Germany.
J Thromb Haemost. 2024 Oct;22(10):2692-2701. doi: 10.1016/j.jtha.2024.06.010. Epub 2024 Jun 25.
Acquired hemophilia A (AHA) is an autoimmune bleeding disorder caused by neutralizing antibodies against coagulation factor VIII. Immunosuppressive therapy (IST) is standard of care to eradicate autoantibody production and protect from further bleeding but carries a risk of severe infection and mortality in frail patients with AHA. Recently, emicizumab has been studied for its potential to reduce the need for early and aggressive IST.
To compare outcomes of 2 studies that used either IST (GTH-AH 01/2010; N = 101) or prophylaxis with emicizumab (GTH-AHA-EMI; N = 47) early after diagnosis of AHA.
Baseline characteristics were balanced by propensity score matching. Primary endpoint was the rate of clinically relevant new bleeds during the first 12 weeks; secondary endpoints were adverse events and overall survival.
The negative binominal model-based bleeding rate was 68% lower with emicizumab as compared with IST (incident rate ratio, 0.325; 95% CI, 0.182-0.581). No difference was apparent in the overall frequency of infections (emicizumab 21%, IST 29%) during the first 12 weeks, but infections were less often fatal in emicizumab-treated patients (0%) compared with IST-treated patients (11%). Thromboembolic events occurred less often with emicizumab (2%) than with IST (7%). Overall survival after 24 weeks was better with emicizumab (90% vs 76%; hazard ratio, 0.44; 95%, CI, 0.24-0.81).
Using emicizumab instead of IST in the early phase after initial diagnosis of AHA reduced bleeding and fatal infections and improved overall survival.
获得性血友病 A（AHA）是一种由针对凝血因子 VIII 的中和抗体引起的自身免疫性出血性疾病。免疫抑制疗法（IST）是消除自身抗体产生并防止进一步出血的标准治疗方法，但在患有 AHA 的体弱患者中，IST 会带来严重感染和死亡的风险。最近，艾美赛珠单抗已被研究用于减少早期和积极 IST 的需求。
比较两项研究的结果，这两项研究分别在 AHA 确诊后早期使用 IST（GTH-AH 01/2010；N=101）或预防性使用艾美赛珠单抗（GTH-AHA-EMI；N=47）。
通过倾向评分匹配平衡基线特征。主要终点是在最初 12 周内发生临床相关新出血的发生率；次要终点是不良事件和总生存率。
与 IST 相比，艾美赛珠单抗的出血率采用负二项式模型计算降低了 68%（发生率比，0.325；95%CI，0.182-0.581）。在最初 12 周内，两种治疗方法的感染总频率没有明显差异（艾美赛珠单抗 21%，IST 29%），但艾美赛珠单抗治疗患者的感染致死率（0%）明显低于 IST 治疗患者（11%）。艾美赛珠单抗组的血栓栓塞事件（2%）少于 IST 组（7%）。24 周后，艾美赛珠单抗组的总生存率更好（90%比 76%；风险比，0.44；95%CI，0.24-0.81）。
在 AHA 初始诊断后的早期阶段使用艾美赛珠单抗代替 IST 可减少出血和致命感染，并提高总生存率。
