Alirocumab and Lipid Levels, Inflammatory Biomarkers, Metabolomics, and Safety in Patients Receiving Maintenance Dialysis: The ALIrocumab in DIALysis Study (A Phase 3 Trial to Evaluate the Efficacy and Safety of Biweekly Alirocumab in Patients on a Stable Dialysis Regimen).

Rationale & Objective: The proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor alirocumab is used in the general population to treat dyslipidemia, but little is known about the effects of alirocumab on lipid levels, biomarkers, the metabolome, and safety in individuals receiving maintenance dialysis. Study Design: Patients receiving maintenance dialysis for at least 3 months and with a low-density lipoprotein cholesterol level of >70 mg/dL were treated with alirocumab for 12 weeks. Laboratory measurements, drug levels, and safety assessments were obtained at baseline and every 4 weeks during the trial. Setting & Participants: In an outpatient setting, 14 patients completed the trial. Intervention: The patients were treated with alirocumab at a full dose of 150 mg every 2 weeks for 12 weeks. The patients were asked to report any adverse events every 2 weeks. Outcomes: There were no unexpected adverse events or laboratory abnormalities in this population receiving dialysis. The drug levels were the same as those for a population not receiving dialysis. Results: Alirocumab resulted in a 45% reduction in the low-density lipoprotein cholesterol level (P = 0.005) and a 35% reduction in the apolipoprotein B level (P = 0.06). There were no significant decreases in the levels of triglycerides, C-reactive protein, fibrinogen, or other inflammatory biomarkers tested. There were significant decreases in the levels of 7 ceramide, 5 sphingomyelin, and 5 cholesterol ester species. Limitations: This study was performed in only 14 patients who were administered alirocumab for only 12 weeks. This study did not address alirocumab treatment in patients with chronic kidney disease not receiving maintenance dialysis. Conclusions: Individuals receiving maintenance dialysis had a similar response to the PCSK9 inhibitor alirocumab as patients not receiving dialysis. The levels of inflammatory biomarkers were not clearly decreased by alirocumab, but the levels of ceramides, sphingomyelins, and cholesterol esters were significantly reduced. Trial Registration: Clinical Trials.gov as NCT03480568.