Inflammation
IL-6 inhibition lowers Lp(a), meta-analysis of 10 studies and 1,201 patients (Am J Prev Cardiol 2026)
Original title: Effect of IL-6 inhibition on lipoprotein(a) levels: A systematic review and meta-analysis
Systematic review and meta-analysis of 10 studies (1,201 participants, from 96 records screened) assessing the effect of anti-IL-6/IL-6 receptor monoclonal antibodies on Lp(a). IL-6 inhibition significantly reduced Lp(a) versus baseline at 2-3 months (standardised mean difference -0.29, 95% CI -0.44 to -0.14, I2 33%) and 6 months (SMD -0.33, 95% CI -0.51 to -0.15, I2 0%). Compared with TNF inhibitors or placebo, IL-6 inhibition produced larger Lp(a) reductions at 2-3 months (SMD -0.49, 95% CI -0.73 to -0.24, I2 63%) and 6 months (SMD -0.97, 95% CI -1.16 to -0.77, I2 0%). The authors conclude anti-IL-6/IL-6R therapy meaningfully lowers Lp(a) relative to controls, a finding that warrants testing in dedicated cardiovascular outcome trials.
Original abstract
Background: Inhibition of interleukin (IL)-6 signaling by monoclonal antibodies (mAb) inhibits apolipoprotein(a) synthesis and reduces circulating lipoprotein(a) [Lp(a)] levels.
Aims: The aims of this systematic literature review and meta-analysis were to summarize clinical evidence for and quantify the effect of anti-IL--6/IL-6 receptor (IL-6R) treatment on Lp(a) levels. Secondary inflammatory and lipid endpoints were also examined.
Methods: Searches were conducted using Embase, PubMed and Cochrane Library databases to identify studies reporting changes in Lp(a) levels following repeat doses of anti-IL-6/IL-6R mAbs. A random-effects meta-analysis compared the effect of IL-6 inhibition vs comparator on Lp(a) levels. A pre--post analysis assessed the effect of IL-6 inhibition on Lp(a) levels before and after treatment. Subgroup analyses by disease type, IL-6 inhibition agent, and comparators were conducted.
Results: Out of 96 records, 10 studies with 1,201 participants were included. IL-6 inhibition was associated with significant reductions in Lp(a) levels vs baseline at 2-3 months (standardized mean difference [SMD] -0.29; 95% CI -0.44 to -0.14; P = .0002; I2 = 33%) and 6 months (SMD -0.33; 95% CI -0.51 to -0.15; P = .0003; I2 = 0%). Compared with tumor necrosis factor inhibitors or placebo, IL-6 inhibition showed greater Lp(a) reductions at 2-3 months (SMD -0.49; 95% CI -0.73 to -0.24; P = .0001; I2 = 63%) and 6 months (SMD --0.97; 95% CI -1.16 to -0.77; P < .00001; I2 = 0%).
Conclusions: This meta-analysis demonstrates significant reductions in Lp(a) levels with anti-IL--6/IL-6R therapy vs controls. The relevance of these findings warrants investigation in cardiovascular outcome trials.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 17 August 2026. Methods.