复发/难治性自身免疫性溶血性贫血的新药治疗现状

Current status of new drug therapy for relapsed/refractory autoimmune hemolytic anemia

自身免疫性溶血性贫血(AIHA)是由于体内产生红细胞自身抗体破坏红细胞的一类免疫性血细胞减少症,该病具有易复发、难治愈的特点。根据自身抗体引起溶血性贫血的特性,AIHA可分为温抗体型AIHA(wAIHA)、冷抗体型AIHA(cAIHA)及温、冷双抗体混合型AIHA 3种类型。近年来,针对复发/难治性AIHA的新药发展迅速。治疗复发/难治性wAIHA的新药主要包括靶向参与AIHA发病过程的浆细胞、B细胞、T细胞和巨噬细胞等免疫细胞的药物,如硼替佐米、依鲁替尼、阿伦单抗、福他替尼等,以及抑制参与溶血过程补体活性的药物,如依库丽珠单抗等。治疗复发/难治性cAIHA的新药主要是抑制补体活性的药物,如依库丽珠单抗、TNT003、苏替莫单抗等。新药对复发/难治性AIHA具有一定疗效,但是需要大样本临床研究进一步验证。为了进一步了解复发/难治性AIHA的药物治疗,尤其是新型靶向药物的应用,笔者拟就新药治疗复发/难治性AIHA的剂量、疗效及不良反应等研究新进展进行阐述。

Autoimmune hemolytic anemia(AIHA),a kind of immune cytopenia that destroyed red blood cells by erythrocyte autoantibodies,is easy to relapse and hard to cure.AIHA can be divided into 3 groups based on the characteristics of antibody causing hemolytic anemia,including warm AIHA(wAIHA),cold AIHA(cAIHA)and mixed AIHA.In recent years,new drugs in treatment of relapsed/refractory AIHA have been developed rapidly.A variety of new drugs in treatment of relapsed/refractory wAIHA are mainly aimed at plasma cells,B cells,T cells and macrophages which involved in pathogenesis of AIHA,such as bortezomib,ibrutinib,alemtuzumab,fostamatinib,etc.,and complements which play an important role in hemolysis,such as eculizumab,etc..New drugs in treatment of relapsed/refractory cAIHA mainly inhibit complement activity,such as eculizumab,TNT003,sutimlimab,etc..All new drugs have certain efficacy on relapsed/refractory AIHA,but it need to be further verified by clinical researches with larger samples in the future.In order to fully understand drug therapy of relapsed/refractory AIHA,especially application of new drugs in targeted therapies,this review showcases advances in dosage,efficacy and adverse reactions of new drugs in treatment of relapsed/refractory AIHA.