Alirocumab in patients with heterozygous familial hypercholesterolaemia undergoing lipoprotein apheresis: the ODYSSEY ESCAPE trial

Patrick M. Moriarty, Klaus G. Parhofer, Stephan P. Babirak, Marc Andre Cornier, Paul Duell, Bernd Hohenstein, Josef Leebmann, Wolfgang Ramlow, Volker Schettler, Vinaya Simha, Elisabeth Steinhagen-Thiessen, Paul D. Thompson, Anja Vogt, Berndt von Stritzky, Yunling Du, Garen Manvelian

Research output: Contribution to journalArticle

97 Citations (Scopus)

Abstract

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 150 mg (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) mean ± SE (95% confidence interval [CI]) per cent change in pre-apheresis LDL-C from baseline at week 6 was -53.7 ± 2.3 (-58.2 to - 49.2) compared with 1.6 ± 3.1 (-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, alirocumab-treated 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.

Original languageEnglish (US)
Pages (from-to)3588-3595
Number of pages8
JournalEuropean Heart Journal
Volume37
Issue number48
DOIs
StatePublished - Dec 21 2016

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Hyperlipoproteinemia Type II
Blood Component Removal
Lipoproteins
Placebos
LDL Cholesterol
alirocumab
Therapeutics
Confidence Intervals
Least-Squares Analysis
Double-Blind Method
Appointments and Schedules

Keywords

  • Alirocumab
  • Familial hypercholesterolaemia
  • Low-density lipoprotein cholesterol
  • Low-density lipoprotein receptor
  • Monoclonal antibody
  • Proprotein convertase subtilisin/kexin type 9

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Alirocumab in patients with heterozygous familial hypercholesterolaemia undergoing lipoprotein apheresis : the ODYSSEY ESCAPE trial. / Moriarty, Patrick M.; Parhofer, Klaus G.; Babirak, Stephan P.; Cornier, Marc Andre; Duell, Paul; Hohenstein, Bernd; Leebmann, Josef; Ramlow, Wolfgang; Schettler, Volker; Simha, Vinaya; Steinhagen-Thiessen, Elisabeth; Thompson, Paul D.; Vogt, Anja; von Stritzky, Berndt; Du, Yunling; Manvelian, Garen.

In: European Heart Journal, Vol. 37, No. 48, 21.12.2016, p. 3588-3595.

Research output: Contribution to journalArticle

Moriarty, PM, Parhofer, KG, Babirak, SP, Cornier, MA, Duell, P, Hohenstein, B, Leebmann, J, Ramlow, W, Schettler, V, Simha, V, Steinhagen-Thiessen, E, Thompson, PD, Vogt, A, von Stritzky, B, Du, Y & Manvelian, G 2016, 'Alirocumab in patients with heterozygous familial hypercholesterolaemia undergoing lipoprotein apheresis: the ODYSSEY ESCAPE trial', European Heart Journal, vol. 37, no. 48, pp. 3588-3595. https://doi.org/10.1093/eurheartj/ehw388
Moriarty, Patrick M. ; Parhofer, Klaus G. ; Babirak, Stephan P. ; Cornier, Marc Andre ; Duell, Paul ; Hohenstein, Bernd ; Leebmann, Josef ; Ramlow, Wolfgang ; Schettler, Volker ; Simha, Vinaya ; Steinhagen-Thiessen, Elisabeth ; Thompson, Paul D. ; Vogt, Anja ; von Stritzky, Berndt ; Du, Yunling ; Manvelian, Garen. / Alirocumab in patients with heterozygous familial hypercholesterolaemia undergoing lipoprotein apheresis : the ODYSSEY ESCAPE trial. In: European Heart Journal. 2016 ; Vol. 37, No. 48. pp. 3588-3595.
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abstract = "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 150 mg (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) mean ± SE (95{\%} confidence interval [CI]) per cent change in pre-apheresis LDL-C from baseline at week 6 was -53.7 ± 2.3 (-58.2 to - 49.2) compared with 1.6 ± 3.1 (-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, alirocumab-treated 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.",
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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, Paul

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

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 150 mg (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) mean ± SE (95% confidence interval [CI]) per cent change in pre-apheresis LDL-C from baseline at week 6 was -53.7 ± 2.3 (-58.2 to - 49.2) compared with 1.6 ± 3.1 (-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, alirocumab-treated 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 150 mg (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) mean ± SE (95% confidence interval [CI]) per cent change in pre-apheresis LDL-C from baseline at week 6 was -53.7 ± 2.3 (-58.2 to - 49.2) compared with 1.6 ± 3.1 (-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, alirocumab-treated 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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