Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, a novel class of monoclonal antibodies, reduces low-density lipoprotein cholesterol levels and improves cardiovascular outcomes. Given the short time frame, these agents have been available for use; reports of nonresponse to the PCSK9 inhibitor therapy are scarce in literature. We describe 2 cases with substantially lesser than expected low-density lipoprotein cholesterol lowering on PCSK9 therapy. Nonresponse to PCSK9 inhibition was attributed to autosomal recessive hypercholesterolemia (secondary to low-density lipoprotein receptor adaptor protein 1 mutation) and plasmapheresis after PCSK9 inhibitor drug injections. Additional PCSK9 inhibitor nonresponders are likely to emerge as the use of these agents increases overtime.

前蛋白转化酶枯草杆菌蛋白酶/ kexin 9型（PCSK9）抑制剂是一类新型的单克隆抗体，可降低低密度脂蛋白胆固醇水平并改善心血管疾病的预后。在较短的时间范围内，这些代理已可供使用。文献中对PCSK9抑制剂治疗无反应的报道很少。我们描述了2例PCSK9治疗降低的低密度脂蛋白胆固醇明显低于预期的病例。对PCSK9抑制的无反应归因于注射PCSK9抑制剂药物后常染色体隐性高胆固醇血症（继发于低密度脂蛋白受体衔接蛋白1突变）和血浆置换。随着这些试剂的使用时间的增加，可能还会出现其他PCSK9抑制剂无反应者。