Comparative Efficacy and Safety of Four Novel Monoclonal Antibody PCSK9 Inhibitors: A Bayesian Network Meta‐Analysis of Lipid and Safety Outcomes

BACKGROUND: Four novel monoclonal antibody proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors-tafolecimab, ongericimab, ebronucimab, and recaticimab-lower low-density lipoprotein cholesterol (LDL-C) in placebo-controlled trials but have never been compared head to head. METHODS: We searched PubMed, Embase, Scopus, CENTRAL, and ClinicalTrials.gov from inception to 8 June 2026 and performed a Bayesian random-effects network meta-analysis of randomized placebo-controlled trials across eight lipid outcomes, analyzed by dose-interval regimen, and adverse events, analyzed by drug (PROSPERO CRD420261422519). Risk of bias was assessed with RoB 2 and certainty of evidence with CINeMA. Lipid effects are placebo-adjusted differences in percentage change from baseline with 95% credible intervals (CrIs). RESULTS: Thirteen trials were included. In the LDL-C network (4,517 patients; 16 regimens), every regimen lowered LDL-C (-45.2% to -80.2%), with concordant reductions in non-high-density lipoprotein cholesterol, apolipoprotein B, and total cholesterol. Most between-agent differences were small, but some indirect contrasts had CrIs excluding zero; most consistently, ongericimab 150 mg every 2 weeks lowered LDL-C more than the three phase 3 recaticimab regimens (differences -14.4% to -18.6%), robust to adjustment for background statin therapy and baseline LDL-C. Rank intervals were wide. The largest triglyceride and high-density lipoprotein cholesterol effects of recaticimab were confined to small phase 1b/2 regimens. No agent differed from placebo for any adverse event or serious adverse events, although information was limited; injection-site reactions were more frequent with active treatment. Certainty of evidence was moderate to very low versus placebo and very low between agents. CONCLUSIONS: All four antibodies produced substantial reductions in atherogenic lipids without a detected safety signal beyond injection-site reactions. Indirect between-agent differences are hypothesis-generating and do not establish a hierarchy; head-to-head and cardiovascular outcome trials are needed.