Author + information
- Robert Dufoura,b,
- G. Kees Hovingha,b,
- John Guytona,b,
- Gisle Langsleta,b,
- Marie Baccara-Dineta,b,
- Chantal Din-Bella,b,
- Garen Manveliana,b and
- Michel Farniera,b
Background: Patients with heterozygous familial hypercholesterolemia (HeFH) who completed the 78-week LONG TERM study (LT) of alirocumab (ALI) were eligible to enroll in an open-label study (OLE; NCT01954394). In contrast to previous ODYSSEY studies (where ALI dose was increased automatically if pre-specified LDL-C not achieved at Week 8), in OLE physicians were able to use their own clinical judgement when adjusting ALI dose from 75 to 150 mg every 2 weeks (Q2W).
Methods: This analysis focuses on 214 patients (safety population) who received ALI 150 mg Q2W (with background statin ± other lipid-lowering therapy) in LT then entered OLE after an 8-week off-drug wash-out period. At OLE entry, all patients received ALI 75 mg Q2W. After Week 8, ALI dose adjustment from 75 to 150 mg Q2W was possible at the physician's discretion, until end of treatment period.
Results: At the time of analysis, 103 patients (48%) had their ALI dose increased from 75 to 150 mg Q2W (mITT population). Among the 214 OLE patients, the overall mean baseline LDL-C was 163.7 mg/dL. For the cohort of patients who had the dose increase, mean baseline LDL-C was 193.0 mg/dL, on-treatment LDL-C at Week 8 (all still receiving 75 mg Q2W) was 118.2 mg/dL (38.7% reduction from baseline), and at Week 48 LDL-C (following dose increase) was 96.6 mg/dL (48.3% reduction; absolute mean LDL-C reduction 96.2 mg/dL). For patients who remained on ALI 75 mg Q2W (n=108), mean baseline LDL-C was 135.0 mg/dL, Week 8 LDL-C was 59.9 mg/dL (56.5% reduction) and Week 48 LDL-C was 64.9 mg/dL (52.6% reduction; absolute mean LDL-C reduction of 69.2 mg/dL). With the ALI dosing strategy in OLE, 2.8% of patients had two consecutive (≥21 days apart) LDL-C values <25 mg/dL; in contrast, for the same cohort during the parent LONG TERM study (150 mg Q2W only), 16.8% had two consecutive LDL-C values <25 mg/dL. Common treatment-emergent adverse events (assessed in all patients in OLE over ∼12 months) were influenza (11.2%), nasopharyngitis (10.7%), back pain (7.0%) and upper respiratory tract infection (6.5%).
Conclusions: In a real-world setting, ALI dose titration provides LDL-C lowering individualized according to patients’ baseline LDL-C, reducing the occurrence of LDL-C <25 mg/dL.
Poster Hall, Hall C
Friday, March 17, 2017, 10:00 a.m.-10:45 a.m.
Session Title: Advances in Cholesterol Measurement and Management
Abstract Category: 32. Prevention: Clinical
Presentation Number: 1106-057
- 2017 American College of Cardiology Foundation