P5382PEARL, a non-interventional study on real-world use of alirocumab in German clinical practice: final study and cardiovascular subgroup data

Abstract

Background: The updated 2017 ESC/EAS Task Force guidance recommends that PCSK9 inhibitors should be considered for patients with atherosclerotic cardiovascular (CV) disease who are not adequately treated with maximally tolerated statins. Purpose: The PEARL (Prospektive Nicht-Interventionelle Studie zur Erfassung der WirksAmkeit und VeRträgLichkeit des PCSK9-Inhibitors PRALUENT) study assessed efficacy and safety of the PCSK9 inhibitor alirocumab (ALI) in patients with hypercholesterolaemia in a real-world setting. Here, we present data from the overall PEARL population and from those with coronary heart disease (CHD) or acute coronary syndrome (ACS). Methods: PEARL was an open, prospective, multicentre, non-interventional study conducted in Germany. Enrolled patients (n=619) had LDL-C >1.81 or 2.59 mmol/L (70 or 100 mg/dL; depending on CV risk) despite maximal tolerated non-ALI lipid-lowering therapies (LLTs), and subsequently received >1 dose of ALI 75 or 150 mg every 2 weeks (Q2W) prior to study enrolment. All patients received ALI. ALI dose was adjusted based on physicians' clinical judgment throughout the study (duration: 24 weeks). Data were documented based on case report forms. The primary efficacy endpoint was LDL-C reduction from baseline (LDL-C prior to ALI therapy) to Week 24. Results: Most patients (72.4%) had a history of CHD and 33.0% were post-ACS. Overall, 45.3% were statin intolerant (unable to tolerate >2 statins) and 27.6% were partially statin intolerant (unable to tolerate sufficient statin dose to reach treatment target). Before the start of ALI therapy, 23.5% of patients were on statin therapy only, 47.8% were on LLT (ezetimibe, fibrates and/or bile acid seques-trants) combined with statin, 10.1% were on non-statin LLT combination therapy and 1.9% were on other LLTs; no information was available for 16.7%. In total, 13.7% of patients with CHD and 16.7% with ACS received >1 statin. Overall, ini-tial ALI dose was 75 mg Q2W in 72.9% of patients and 150 mg Q2W in 24.5%, with similar percentages observed for patients with CHD (72.2% and 25.3%, respectively) and ACS (74.3% and 23.8%). Week 24 LDL-C levels are presented in Figure 1. Least-squares mean percentage changes from baseline to Week 24 in LDL-C were-48.6% for all patients,-50.0% for those with CHD and-50.4% for those with ACS. During the study, 20.4% of all patients received dose increase from 75 mg to 150 mg Q2W and 4.0% had a dose decrease from 150 mg to [Figure Presented] 75 mg Q2W. Similar percentages were seen for patients with CHD (20.5% and 1.8%, respectively) and ACS (19.8% and 2.0%). Treatment-emergent adverse events were reported in 10.3% of patients, with myalgia (7.3%) the most com-mon; 13.4% of patients discontinued therapy. Conclusions: PEARL showed that, in a real-world setting, ALI significantly re-duced LDL-C levels in patients with high CV risk, including those with CHD and ACS. ALI efficacy and safety were consistent with those observed in the ODYSSEY Phase 3 programme. Funding Acknowledgements: Sanofi and Regeneron Pharmaceuticals, Inc.