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

被引：151

作者：

Moriarty, Patrick M. ^{[1
]}

Parhofer, Klaus G. ^{[2
]}

Babirak, Stephan P. ^{[3
]}

Cornier, Marc-Andre ^{[4
]}

Duell, P. Barton ^{[5
]}

Hohenstein, Bernd ^{[6
]}

Leebmann, Josef ^{[7
]}

Ramlow, Wolfgang ^{[8
]}

Schettler, Volker ^{[9
]}

Simha, Vinaya ^{[10
]}

Steinhagen-Thiessen, Elisabeth ^{[11
]}

Thompson, Paul D. ^{[12
]}

Vogt, Anja ^{[13
]}

von Stritzky, Berndt ^{[14
]}

Du, Yunling ^{[15
]}

Manvelian, Garen ^{[16
]}

机构：

[1] Univ Kansas, Div Clin Pharmacol, Dept Internal Med, Med Ctr, 3901 Rainbow Blvd, Kansas City, KS 66160 USA

[2] Univ Munich, Med Dept 2, Marchioninistr 15, D-81377 Munich, Germany

[3] Metab Leader LLC, 71 US Route 1 Suite J, Scarborough, ME 04074 USA

[4] Anschutz Hlth & Wellness Ctr, Div Endocrinol Metab & Diabet, Anschutz Med Campus, Aurora, CO 80045 USA

[5] Oregon Hlth & Sci Univ, Knight Cardiovasc Inst, 3181 SW Sam Jackson Pk Rd,L607, Portland, OR 97239 USA

[6] Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Dept Internal Med 3, Extracorporeal Treatment & Lipoprot Apheresis Ctr, D-01069 Dresden, Germany

[7] Apherese Zentrum Passau, Innstr 76, D-94032 Passau, Germany

[8] Apheresis Ctr Rostock, Nobelstr 53, D-18059 Rostock, Germany

[9] Nehrol Zentrum Gottingen GbR, Apheresis Ctr, Lutter 24, D-37075 Gottingen, Germany

[10] Mayo Clin, 200 First St SW, Rochester, MN 55905 USA

[11] Charite, Campus Virchow Klinikum, Augustenburger Pl 1,Ostring 3, D-13353 Berlin, Germany

[12] Hartford Hosp, Cardiol, 80 Seymour St,JB722, Hartford, CT 06102 USA

[13] Univ Munich, LMU Klinikum, Med Klin & Poliklin 4, D-81377 Munich, Germany

[14] Sanofi Aventis Deutschland GmbH, Dept Med, Potsdamer Str 8, D-10785 Berlin, Germany

[15] Regeneron Pharmaceut Inc, 110 Allen Rd, Basking Ridge, NJ 07920 USA

[16] Regeneron Pharmaceut Inc, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA

来源：

EUROPEAN HEART JOURNAL | 2016年 / 37卷 / 48期

关键词：

Alirocumab; Familial hypercholesterolaemia; Low-density lipoprotein cholesterol; Monoclonal antibody; Proprotein convertase subtilisin/kexin type 9; Low-density lipoprotein receptor; RANDOMIZED CONTROLLED-TRIAL; MONOCLONAL-ANTIBODY; LDL-APHERESIS; ATORVASTATIN; CHOLESTEROL; EFFICACY; SAFETY; PCSK9; MANAGEMENT; EZETIMIBE;

D O I：

10.1093/eurheartj/ehw388

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 1.663.1 (-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, 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.

引用

页码：3588 / 3595

页数：8