Long-term treatment adherence to the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab in 6 ODYSSEY Phase III clinical studies with treatment duration of 1 to 2 years

Abstract

Nonadherence to cardiovascular medications, including daily, oral statin therapy, negatively impacts outcomes in patients requiring low-density lipoprotein cholesterol (LDL-C)-lowering therapy. The proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab also reduces LDL-C, but has a different mode of administration (subcutaneous injection). The objective of the study was to assess long-term adherence to alirocumab 75 or 150mg, given every 2weeks, in phase III trials of patients with sub-optimally controlled hypercholesterolemia. Data were pooled from 6 ODYSSEY trials (n=4212) with double-blind treatment durations of 52 to 104weeks. Adherence was reported as percentage of days receiving injections according to dosing schedule and categorized into 100% adherence, below-planned dosing, above-planned dosing, and both below- and above-planned dosing. Overall adherence was calculated as 100- (percentage of days with below-planned dosing+percentage of days with above-planned dosing). Safety of alirocumab and effect on LDL-C levels were also evaluated. Adherence was analyzed for 4197 patients (n=2786 alirocumab; n=1411 control). Mean overall adherence was high (alirocumab 98.0%; control 97.8%). Among patients receiving alirocumab, 45.7% were 100% adherent, 20.4% had below-planned dosing, 2.9% had above-planned dosing, and 31.1% had both below- and above-planned dosing. Mean percentage reduction in LDL-C (baseline to Week 52) was 45.8% to 61.9%, depending on alirocumab dose, and was comparable across adherence categories. Treatment-emergent adverse events leading to alirocumab discontinuation were infrequent and included myalgia and injection-site reactions (<1% each). Alirocumab injections were associated with a high level of adherence over ≥1year. Infrequent below- or above-planned dosing had minimal impact on LDL-C reductions.