Impact of PCSK9 monoclonal antibodies on circulating hs-CRP levels: a systematic review and meta-analysis of randomised controlled trials

Abstract

Objective: 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.

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

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

Eligibility criteria for selecting studies: All randomised controlled trials that reported changes of hs-CRP were included.

Results: 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).

Conclusions: 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.

Keywords: PCSk9; hs-CRP; meta-analysis; monoclonal antibody.

Figure 1

Flow diagram of selection of studies.

Figure 2

Forest plots depicting the effect of PCSK9-mAbs on hs-CRP. PCSK9-mAb, proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibody; hs-CRP, high-sensitivity C-reactive protein.

Figure 3

Subgroup analyses of the effect of PCSK9-mAbs on hs-CRP. PCSK9-mAb, proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibody; hs-CRP, high-sensitivity C-reactive protein; FH, familial hypercholesterolaemia; non-FH, non-familial hypercholesterolaemia.