TY - JOUR
T1 - Alirocumab in patients with heterozygous familial hypercholesterolaemia undergoing lipoprotein apheresis
T2 - The ODYSSEY ESCAPE trial
AU - Moriarty, Patrick M.
AU - Parhofer, Klaus G.
AU - Babirak, Stephan P.
AU - Cornier, Marc Andre
AU - Duell, P. Barton
AU - Hohenstein, Bernd
AU - Leebmann, Josef
AU - Ramlow, Wolfgang
AU - Schettler, Volker
AU - Simha, Vinaya
AU - Steinhagen-Thiessen, Elisabeth
AU - Thompson, Paul D.
AU - Vogt, Anja
AU - Von Stritzky, Berndt
AU - Du, Yunling
AU - Manvelian, Garen
N1 - Publisher Copyright:
© The Author 2016.
PY - 2016/12/21
Y1 - 2016/12/21
N2 - Aim: To evaluate the effect of alirocumab on frequency of standard apheresis treatments [weekly or every 2 weeks (Q2W)] in heterozygous familial hypercholesterolaemia (HeFH). Methods and results: ODYSSEY ESCAPE (NCT02326220) was a double-blind study in 62 HeFH patients undergoing regular weekly or Q2W lipoprotein apheresis. Patients were randomly assigned (2:1, respectively) to receive alirocumab 150mg (n=41) or placebo (n=21) Q2W subcutaneously for 18 weeks. From day 1 to week 6, apheresis rate was fixed according to the patient's established schedule; from weeks 7 to 18, apheresis rate was adjusted based on the patient's low-density lipoprotein cholesterol (LDL-C) response in a blinded fashion. Apheresis was not performed when the LDL-C value was-30% lower than the baseline (pre-apheresis) value. The primary efficacy endpoint was the rate of apheresis treatments over 12 weeks (weeks 7-18), standardized to number of planned treatments. In the alirocumab group the least square (LS) mean6SE (95% confidence interval [CI]) per cent change in pre-apheresis LDL-C from baseline at week 6 was-53.762.3 (-58.2 to-49.2) compared with 1.663.1 (-4.7 to 7.9) in the placebo group. The primary efficacy endpoint showed statistically significant benefit in favour of alirocumab (Hodges-Lehmann median estimate of treatment difference: 0.75; 95% CI 0.67-0.83; P<0.0001). Therefore, alirocumabtreated patients had a 0.75 (75%) additional reduction in the standardized rate of apheresis treatments vs. placebo-treated patients. During this period, 63.4% of patients on alirocumab avoided all and 92.7% avoided at least half of the apheresis treatments. Adverse event rates were similar (75.6% of patients on alirocumab vs. 76.2% on placebo). Conclusions: Lipoprotein apheresis was discontinued in 63.4% of patients on alirocumab who were previously undergoing regular apheresis, and the rate was at least halved in 92.7% of patients. Alirocumab was generally safe and well tolerated.
AB - Aim: To evaluate the effect of alirocumab on frequency of standard apheresis treatments [weekly or every 2 weeks (Q2W)] in heterozygous familial hypercholesterolaemia (HeFH). Methods and results: ODYSSEY ESCAPE (NCT02326220) was a double-blind study in 62 HeFH patients undergoing regular weekly or Q2W lipoprotein apheresis. Patients were randomly assigned (2:1, respectively) to receive alirocumab 150mg (n=41) or placebo (n=21) Q2W subcutaneously for 18 weeks. From day 1 to week 6, apheresis rate was fixed according to the patient's established schedule; from weeks 7 to 18, apheresis rate was adjusted based on the patient's low-density lipoprotein cholesterol (LDL-C) response in a blinded fashion. Apheresis was not performed when the LDL-C value was-30% lower than the baseline (pre-apheresis) value. The primary efficacy endpoint was the rate of apheresis treatments over 12 weeks (weeks 7-18), standardized to number of planned treatments. In the alirocumab group the least square (LS) mean6SE (95% confidence interval [CI]) per cent change in pre-apheresis LDL-C from baseline at week 6 was-53.762.3 (-58.2 to-49.2) compared with 1.663.1 (-4.7 to 7.9) in the placebo group. The primary efficacy endpoint showed statistically significant benefit in favour of alirocumab (Hodges-Lehmann median estimate of treatment difference: 0.75; 95% CI 0.67-0.83; P<0.0001). Therefore, alirocumabtreated patients had a 0.75 (75%) additional reduction in the standardized rate of apheresis treatments vs. placebo-treated patients. During this period, 63.4% of patients on alirocumab avoided all and 92.7% avoided at least half of the apheresis treatments. Adverse event rates were similar (75.6% of patients on alirocumab vs. 76.2% on placebo). Conclusions: Lipoprotein apheresis was discontinued in 63.4% of patients on alirocumab who were previously undergoing regular apheresis, and the rate was at least halved in 92.7% of patients. Alirocumab was generally safe and well tolerated.
KW - Alirocumab
KW - Familial hypercholesterolaemia
KW - Low-density lipoprotein cholesterol
KW - Low-density lipoprotein receptor
KW - Monoclonal antibody
KW - Proprotein convertase subtilisin/kexin type 9
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U2 - 10.1093/eurheartj/ehw388
DO - 10.1093/eurheartj/ehw388
M3 - Article
C2 - 27572070
AN - SCOPUS:85014503636
SN - 0195-668X
VL - 37
SP - 3588
EP - 3595
JO - European heart journal
JF - European heart journal
IS - 48
ER -