RESUMO
BACKGROUND: Despite optimal treatment, a residual inflammatory risk often remains in patients with atherosclerotic cardiovascular disease. In a US-based phase 2 trial, ziltivekimab, a fully human monoclonal antibody targeting the interleukin-6 ligand, significantly reduced biomarkers of inflammation compared with placebo in patients at high atherosclerotic risk. Here, we report the efficacy and safety of ziltivekimab in Japanese patients. METHODS: RESCUE-2 was a randomized, double-blind, 12-week, phase 2 trial. Participants aged ≥20â¯years with stage 3-5 non-dialysis-dependent chronic kidney disease and high-sensitivity C-reactive protein (hsCRP) ≥2â¯mg/L were randomized to receive placebo (nâ¯=â¯13) or subcutaneous ziltivekimab 15â¯mg (nâ¯=â¯11) or 30â¯mg (nâ¯=â¯12) at Weeks 0, 4, and 8. The primary endpoint was percentage change in hsCRP levels from baseline to end of treatment (EOT; mean of Week 10 and Week 12 values). RESULTS: At EOT, median hsCRP levels were reduced by 96.2â¯% in the 15â¯mg group (pâ¯<â¯0.0001 versus placebo), by 93.4â¯% in the 30â¯mg group (pâ¯=â¯0.002 versus placebo), and by 27.0â¯% in the placebo group. Serum amyloid A and fibrinogen levels were also reduced significantly. Ziltivekimab was well tolerated and did not affect total cholesterol to high-density lipoprotein cholesterol ratios. There was a small, but statistically significant increase in triglyceride levels with ziltivekimab 15â¯mg and 30â¯mg compared with placebo. CONCLUSIONS: The efficacy and safety results support the development of ziltivekimab for secondary prevention and the treatment of patients at high atherosclerotic risk. CLINICALTRIALS: gov identifier, NCT04626505.