移植物抗宿主病治疗药物临床研发与评价的思考

Reflections on clinical development and evaluation of drugs for graft-versushost disease treatment

移植物抗宿主病(GvHD)是异基因造血干细胞移植(Allo-HSCT)后主要的并发症和死亡原因。根据临床特征GvHD主要分为急性GvHD和慢性GvHD,可累及皮肤、肝脏、胃肠道等全身多个器官,是一种严重且异质性高的疾病。糖皮质激素是GvHD一线系统治疗,激素难治GvHD的患者预后较差。近年来,GvHD新药研发成为热点,伊布替尼、芦可替尼、贝舒地尔相继在国际获批用于GvHD二线和/或后线治疗用药,国内也有多个创新药正处于临床研发阶段。在总结近年上市药物临床研发经验以及国外监管考量的基础上,从技术审评角度,结合GvHD临床需求、疾病和药物特点、国内外差异等,对GvHD治疗药物的临床研发和评价中关注的重点内容进行讨论,以期为此类药物的临床研发和评价提供参考,加快创新药物研发。

Graft-versus-host disease(GvHD)is a major complication and cause of death in allogeneic hematopoietic stem cell transplantation recipients.According to clinical characteristics,it is mainly divided into acute GvHD and chronic GvHD,which may impair multiple organs such as skin,liver,and gastrointestinal tract.GvHD is a serious and highly heterogeneous disease.Corticosteroids are the first-line systemic treatment for GvHD,and steroid refractory GvHD patients have a poor prognosis.In recent years,the development of GvHD new drugs has become a hot topic.Ibrutinib,ruxolitinib,and belumosudil have been approved for the treatment of GvHD over the world.There are also several innovative drugs in different phases of clinical trials in China.This paper summarizes the clinical development experiences of recently listed drugs and the regulatory considerations of foreign countries.Some considerations are put forward from the perspective of drug evaluation based on clinical needs,disease and drug characteristics,differences at home and abroad,in order to provide reference for the clinical research and evaluation.