Effects on lipids and pharmacokinetics parameters of PCSK9 mabs in a real life setting high CV risk patients

Abstract

Background and Aims : To investigate PCSK9-inhibitor mAbs kinetics and possible correlations between blood levels of total, free and monoclonal antibodies (mAbs)-bound forms of PCSK9 in a group of high CV risk patients.Methods: Blood samples were obtained from 56 patients (32 men, 24 women) 7 days after administration of PCSK9-i mAbs (Evolocumab or Alirocumab), and again after a wash-out period of 3-4 weeks or before starting therapy. Full lipid profile and total/free-PCSK9 plasma levels were measured by two ELISA assays: a standard ELISA assay for total PCSK9, and in house developed ELISA assay for free-PCSK9. The treatment effects were evaluated as Δ and Δ% of the means. Data were analyzed by paired t-test and the Wilcoxon test.Results: PCSK9 mAbs decreased TC by 38%; LDL-C by 53%; TG by 17%; non-HDL-C by 50%, and Lp(a) by 15% (p<0.05 for all variables); HDL-C increased by 5%. On treatment circulating total PCSK9 values increased by 3.34 fold (p<0.05), and free-PCSK9 decreased by 20% (p<0.05) with some differences between the two drugs. Four patients were “hypo-responders” with an LDL-C reduction <15%.Conclusions: In a real-life setting, mAbs effects on LDL-C, non-HDL-C and Lp(a) were comparable to those observed in large clinical trials (FOURIER, ODYSSEY OUTCOMES). Interestingly, PCSK9 plasma values measured 3-4 weeks after last injection show a significant residual effect of PCSK9 mAbs. It is plausible to hypothesize the development of an algorithm using total/free/bound PCSK9 assays to define both adherence to therapy and hypo-responders patients. Background and Aims : To investigate PCSK9-inhibitor mAbs kinetics and possible correlations between blood levels of total, free and monoclonal antibodies (mAbs)-bound forms of PCSK9 in a group of high CV risk patients. Methods: Blood samples were obtained from 56 patients (32 men, 24 women) 7 days after administration of PCSK9-i mAbs (Evolocumab or Alirocumab), and again after a wash-out period of 3-4 weeks or before starting therapy. Full lipid profile and total/free-PCSK9 plasma levels were measured by two ELISA assays: a standard ELISA assay for total PCSK9, and in house developed ELISA assay for free-PCSK9. The treatment effects were evaluated as Δ and Δ% of the means. Data were analyzed by paired t-test and the Wilcoxon test. Results: PCSK9 mAbs decreased TC by 38%; LDL-C by 53%; TG by 17%; non-HDL-C by 50%, and Lp(a) by 15% (p<0.05 for all variables); HDL-C increased by 5%. On treatment circulating total PCSK9 values increased by 3.34 fold (p<0.05), and free-PCSK9 decreased by 20% (p<0.05) with some differences between the two drugs. Four patients were “hypo-responders” with an LDL-C reduction <15%. Conclusions: In a real-life setting, mAbs effects on LDL-C, non-HDL-C and Lp(a) were comparable to those observed in large clinical trials (FOURIER, ODYSSEY OUTCOMES). Interestingly, PCSK9 plasma values measured 3-4 weeks after last injection show a significant residual effect of PCSK9 mAbs. It is plausible to hypothesize the development of an algorithm using total/free/bound PCSK9 assays to define both adherence to therapy and hypo-responders patients.