Dataset Information

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.

SUBMITTER: Cao YX

PROVIDER: S-EPMC6173233 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Cao Ye-Xuan YX Li Sha S Liu Hui-Hui HH Li Jian-Jun JJ

BMJ open 20181004 9

<h4>Objective</h4>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.<h4>Design</h4>A systematic review and meta-analysis of randomised controlled trials.<h4>Data sources</h4>PubMed, MEDLINE, the Cochrane Library databases, ClinicalTrials.gov and recent conferences were searched from inception to May 2018.<h4>Eligibility criteria for selecting studies</h4>All randomised ...[more]

PMID: 30287608

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Project description:IntroductionConventional lipid-lowering agents, including statins, ezetimibe, fibrates, bile acid sequestrants, nicotinic acid, bempedoic acid and Omega-3, are essential to the management of dyslipidaemia. However, these agents have been shown to increase the level of plasma proprotein convertase subtilisin/kexin 9 (PCSK9), a serine protease associated with increased cardiovascular risk. This review aims to investigate the impact of commonly available conventional lipid-lowering agents on circulating PCSK9 levels and lipid profiles.Methods and analysisThis protocol is conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines. A systematic search will be conducted in the following databases: MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, Web of Science, SCOPUS and ScienceDirect. Additional information will be retrieved from clinical trial registries or from reference list searches. Published and peer-reviewed randomised controlled trials with adults receiving statin, ezetimibe, fibrate, bile acid sequestrant, nicotinic acid, bempedoic acid or Omega-3 monotherapy or in combination for at least 2 weeks, with availability of plasma PCSK9 at the beginning and end of treatment or the net changes in values, will be included. Study selection, data extraction and assessment of the risk of bias will be independently conducted by two investigators. Continuous data will be presented as a standardised mean difference with 95% confidence interval (CI) and dichotomous data as risk ratios with 95% CI. Subgroup analysis and sensitivity analysis will be performed when sufficient studies are included. Publication bias will be assessed with a funnel plot and Egger's test.Ethics and disseminationEthics approval is not required as this review will only include data from published sources. The results will be published in a peer-reviewed journal.Patient and public involvementNo patient or members of the general public are involved.Prospero registration numberCRD42022297942.

Project description:BackgroundAnti-drug antibodies (ADAs) to bococizumab were detected in > 40% of subjects in the SPIRE lipid-lowering trials. The risk of cross-reactivity between anti-bococizumab antibodies and other approved anti-proprotein convertase subtilisin/kexin type-9 (PCSK9) monoclonal antibodies (mAbs) was investigated using a single-assay approach.MethodsBococizumab immunogenicity was assessed in SPIRE-HR, a 52-week study. The highest ADA titer sample from each ADA-positive subject (n = 155) was tested in vitro for cross-reactivity to alirocumab and evolocumab using a novel ADA assay approach. Additional specificity tiers within the bococizumab ADA assay against each drug were validated using recombinant PCSK9 as a surrogate cross-reactive positive control. If the highest ADA titer sample showed cross-reactivity, additional samples from that subject were analyzed. Cross-reactivity was determined by the ability of alirocumab or evolocumab to inhibit the sample signal greater than or equal to the cross-reactivity cut-points.ResultsADAs were detected in 44.0% (155/352) of bococizumab-treated subjects, and 27.0% also developed neutralizing antibodies (NAbs). Median ADA and NAb titers ranged from 276 to 526 and 8 to 12 over the course of the study, respectively. From 155 ADA-positive subjects tested for cross-reactivity, one (0.6%) subject showed weak cross-reactivity to both alirocumab and evolocumab. This cross-reactivity signal was transient (from Days 337 to 373) and undetectable at the last ADA-positive timepoint (Day 407).ConclusionA novel, single-assay approach was validated to assess the potential cross-reactivity of anti-bococizumab antibodies to alirocumab and evolocumab. In subjects who developed ADAs to bococizumab, the likelihood of clinically relevant cross-reactivity to marketed anti-PCSK9 mAbs is remote, based on the low frequency of cross-reactivity observed, which was weak in signal inhibition and transient in nature.Clinical trial registrationThe SPIRE-HR study is registered on ClinicalTrials.gov under the identifier NCT01968954.

Dataset Information

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

Objective

Design

Data sources

Eligibility criteria for selecting studies

Results

Conclusions

Publications

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

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