RG-7652

Objectives. The aim of this study was to provide the first study to systematically analyze the efficacy and safety of PCSK9‐mAbs in the treatment of familial hypercholesterolemia (FH). Methods. A computer was used to search the electronic Cochrane Library, PubMed/MEDLINE, and Embase databases for clinical trials using the following search terms: “AMG 145”, “evolocumab”, “SAR236553/REGN727”, “alirocumab”, “RG7652”, “LY3015014”, “RN316/bococizumab”, “PCSK9”, and “familial hypercholesterolemia” up to November 2020. Study quality was assessed with the Cochrane Collaboration’s tool, and publication bias was evaluated by a contour‐enhanced funnel plot and the Harbord modification of the Egger test. After obtaining the data, a meta‐analysis was performed using R software, version 4.0.3. Results. A meta‐analysis was performed on 7 clinical trials (926 total patients). The results showed that PCSK9‐mAbs reduced the LDL‐C level by the greatest margin, WMD −49.14%, 95% CI: −55.81 to −42.47%, on FH versus control groups. PCSK9‐mAbs also significantly reduced lipoprotein (a) (Lp (a)), total cholesterol (TC), triglycerides (TG), apolipoprotein‐B (Apo‐B), and non‐high‐density lipoprotein cholesterol (non‐HDL‐C) levels and increased HDL‐C and apolipoprotein‐A1 (Apo‐A1) levels of beneficial lipoproteins. Moreover, no significant difference was found between PCSK9‐mAbs treatment and placebo in common adverse events, serious events, and laboratory adverse events. Conclusion. PCSK9‐mAbs significantly decreased LDL‐C and other lipid levels with satisfactory safety and tolerability in FH treatment.

To evaluate the potential effects of proprotein convertase subtilisin/kexin type 9 monoclonal antibody (PCSK9-mAb) on high-sensitivity C reactive protein (hs-CRP) concentrations.

A systematic review and meta-analysis of randomised controlled trials.

PubMed, MEDLINE, the Cochrane Library databases, ClinicalTrials.gov and recent conferences were searched from inception to May 2018.

All randomised controlled trials that reported changes of hs-CRP were included.

Ten studies involving 4198 participants were identified. PCSK9-mAbs showed a slight efficacy in reducing hs-CRP (−0.04 mg/L, 95% CI: −0.17 to 0.01) which was not statistically different. The results did not altered when subgroup analyses were performed including PCSK9-mAb types (alirocumab: 0.12 mg/L, 95% CI: −0.18 to 0.43; evolocumab: 0.00 mg/L, 95% CI: −0.07 to 0.07; LY3015014: −0.48 mg/L, 95% CI: −1.28 to 0.32; RG7652: 0.35 mg/L, 95% CI: −0.26 to 0.96), treatment duration (≤12w: 0.00 mg/L, 95% CI: −0.07 to 0.07; >12w: −0.11 mg/L, 95% CI: −0.45 to −0.23), participant characteristics (familial hypercholesterolaemia: 0.00 mg/L, 95% CI: −0.07 to 0.07; non-familial hypercholesterolaemia: 0.07 mg/L, 95% CI: −0.12 to 0.26; mix: −0.48 mg/L, 95% CI: −1.28 to 0.32) and treatment methods (monotherapy: 0.00 mg/L, −0.08 to 0.07; combination therapy: −0.08 mg/L, −0.37 to 0.21). Meta-regression analyses suggested no significant linear correlation between baseline age (p=0.673), sex (p=0.645) and low-density lipoprotein cholesterol reduction (p=0.339).

Our updated meta-analysis suggested that PCSK9-mAbs had no significant impact on circulating hs-CRP levels irrespective of PCSK9-mAb types, participant characteristics and treatment duration or methods.