Алирокумаб: новые перспективы липидснижающей терапии


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Аннотация

Аннотация Алирокумаб (Пралуэнт) — полностью человеческое моноклональное антитело к пропротеинконвертазе субтилизин/кексин 9-го типа (PCSK9). Согласно данным клинических исследований II и III фазы программы ODYSSEY алирокумаб демонстрирует высокую эффективность в снижении уровня холестерина (ХС) липопротеинов низкой плотности (ЛПНП) у пациентов с первичной гиперхолестеринемией со значительным преимуществом над контрольными группами (плацебо, эзетимиба или модификации терапии статинами) как в монотерапии, так и в комбинации со статинами и другими липидснижающими препаратами. Алирокумаб дает дополнительные гиполипидемические эффекты в отношении других атерогенных фракций ХС, в том числе ХС не липопротеинов высокой плотности, аполипопротеина В и липопротеина (а). Алирокумаб характеризуется высокой безопасностью и хорошей переносимостью и может рассматриваться в качестве препарата выбора у пациентов с недостижением целевых уровней ХС ЛПНП на фоне терапии статинами, непереносимостью статинов и семейной гетерозиготной гиперхолестеринемией. В настоящее время имеются предварительные результаты вторичного анализа данных, полученных в исследовании ODYSSEY LONG TERM, свидетельствующие, что терапия алирокумабом может сопровождаться снижением риска развития сердечно-сосудистых осложнений. Окончательные результаты будут предоставлены после публикации данных исследования по изучению сердечно-сосудистых исходов на фоне терапии алирокумабом по сравнению с плацебо (ODYSSEY OUTCOMES).

Об авторах

Ж Д Кобалава

ФГАОУ ВО «Российский университет дружбы народов»

Москва, Россия

С В Виллевальде

ФГАОУ ВО «Российский университет дружбы народов»

Москва, Россия

М А Воробьева

ФГАОУ ВО «Российский университет дружбы народов»

Москва, Россия

Список литературы

  1. World Health Organization (WHO). Cardiovascular diseases (CVDs) Fact Sheet No. 317. Geneva, Switzerland: WHO; 2015. Reviewed September 2016. http://www.who.int/mediacentre/factsheets/fs317/en/
  2. Olsson AG, Lindahl C, Holme I, et al. LDL cholesterol goals and cardiovascular risk during statin treatment: the IDEAL study. Eur J Cardiovasc Prev Rehabil. 2011;18:262-269. https://doi.org/10.1177/1741826710389391
  3. Martin SS, Blumenthal RS, Miller M. LDL cholesterol: the lower the better. Med Clin North Am. 2012;96:13-26. https://doi.org/10.1016/j.mcna.2012.01.009
  4. Кухарчук В.В., Коновалов Г.А., Галявич А.С. и др. Диагностика и коррекция нарушений липидного обмена с целью профилактики и лечения атеросклероза. Российские рекомендации. V пересмотр. Атеросклероз и дислипидемии. 2012;4:5-61.
  5. Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129:S1-S45. https://doi.org/10.1161/01.cir.0000437738.63853.7a
  6. Catapano AL, De Backer G, Wiklund O, et al. ESC/EAS Guidelines for the management of dyslipidaemias. Eur Heart J. https://doi.org/10.1093/eurheartj/ehw272
  7. Кобалава Ж.Д., Виллевальде С.В., Воробьева М.А. Предикторы раннего ответа на стартовую высокодозовую липидснижающую терапию у пациентов очень высокого сердечно-сосудистого риска. Клиническая фармакология и терапия. 2016; 25(3):37-41.
  8. Zhao S, Wang Y, Mu Y, et al. Prevalence of dyslipidaemia in patients treated with lipid-lowering agents in China: results of the DYSlipidemia International Study (DYSIS). Atherosclerosis. 2014; 235(2):463e9. https://doi.org/10.1016/j.atherosclerosis.2014.05.916
  9. Gitt AK, Drexel H, Feely J, et al. Persistent lipid abnormalities in statin-treated patients and predictors of LDL-cholesterol goal achievement in clinical practice in Europe and Canada. Eur J Prevent Cardiol. 2012;19:221-230. https://doi.org/10.1177/1741826711400545
  10. Boekholdt SM, Hovingh GK, Mora S, et al. Very low levels of atherogenic lipoproteins and the risk for cardiovascular events: a meta-analysis of statin trials. J Am Coll Cardiol. 2014;64:485-94. https://doi.org/10.1016/j.jacc.2014.02.615
  11. Оганов Р.Г., Кухарчук В.В., Арутюнов Г.П., и др. Сохраняющиеся нарушения показателей липидного спектра у пациентов с дислипидемией, получающих статины, в реальной клинической практике в Российской Федерации (российская часть исследования DYSIS). Кардиоваскулярная терапия и профилактика. 2012;11(4):70-78.
  12. Arca M, Pigna G. Treating statin-intolerant patients. Diabetes Metab Syndr Obes. 2011;4:155-166. https://doi.org/10.2147/DMSO.S11244.
  13. Ridker PM, Danielson E, Fonseca FA, et al. Rosuvastatin to Prevent Vascular Events in Men and Women with Elevated C-Reactive Protein. N Engl J Med. 2008;359:2195-2207. https://doi.org/10.1056/NEJMoa0807646
  14. Abd TT, Jacobson TA. Statin-induced myopathy: a review and update. Expert Opin Drug Saf. 2011;10:373-387. https://doi.org/10.1517/14740338.2011.540568
  15. Cohen JD, BrintonEA, ItoMK, et al. Understanding Statin Use in America and Gaps in Patient Education (USAGE): an internet-based survey of 10,138 current and former statin users. J Clin Lipidol. 2012;6:208-215. https://doi.org/10.1016/j.jacl.2012.03.003
  16. Stein, E, Stender, S, Mata P, et al. Achieving lipoprotein goals in patients at high risk with severe hypercholesterolemia: efficacy and safety of ezetimibe co-administered with atorvastatin. Am Heart J. 2004;148:447-455. https://doi.org/10.1016/j.ahj.2004.03.052
  17. Abifadel M, Varret M, Rabes JP, et al. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat Genet. 2003;34: 154-156. https://doi.org/10.1038/ng1161
  18. Cohen J, Pertsemlidis A, Korowski IK, et al. Low LDL cholesterol in individuals of African descent resulting from frequent nonsense mutations in PCSK9. Nat Genet. 2005;37:161-165. https://doi.org/10.1038/ng1509
  19. Cohen JC, Boerwinkle E, Mosley TH Jr, et al. Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N Engl J Med. 2006;354:1264-1272. https://doi.org/10.1056/NEJMoa054013
  20. Benn M, Nordestgaard BG, Grande P, et al. PCSK9 R46L, low-density lipoprotein cholesterol levels, and risk of ischemic heart disease: 3 independent studies and meta-analyses. J Am Coll Cardiol. 2010;55: 2833-2842. https://doi.org/10.1016/j.jacc.2010.02.044
  21. Goldstein J L, Brown M S. History of discovery: the LDL receptor. Arterioscler Thromb Vasc Biol. 2009;29:431-438. https://doi.org/10.1161/ATVBAHA.108.179564
  22. Horton J D, Cohen J C, Hobbs H H. PCSK9: a convertase that coordinates LDL catabolism. J Lipid Res. 2009;50:S172-S177. https://doi.org/10.1194/jlr.R800091-JLR200
  23. Praluent prescribing information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/125559Orig1s000lbledt.pdf
  24. Roth EM, Diller P. Alirocumab for hyperlipidemia: physiology of PCSK9 inhibition, pharmacodynamics and phase I and II clinical trial results of a PCSK9 monoclonal antibody. Future Cardiol. 2014;10:183-199. https://doi.org/10.2217/fca.13.107
  25. Stein EA, Mellis S, Yancopoulos GD, et al. Effect of a monoclonal antibody to PCSK9 on LDL cholesterol. N Engl J Med. 2012; 366(12):1108-1118. https://doi.org/10.1056/NEJMoa1105803
  26. Kűhnast S, van der Hoorn JWA, Pieterman EJ, et al. Alirocumab inhibits atherosclerosis, improves the plaque morphology, and enhances the effects of a statin. J Lipid Res. 2014;55(10):2103-2112. https://doi.org/10.1194/jlr.M051326
  27. Waldmann TA, Strober W. Metabolism of immunoglobulins. Prog Allergy. 1969;13:1-110.
  28. Lunven C, Paehler T, Poitiers F, et al. A randomized study of the relative pharmacokinetics, pharmacodynamics, and safety of alirocumab, a fully human monoclonal antibody to PCSK9, after single subcutaneous administration at three different injection sites in healthy subjects. Cardiovasc Ther. 2014;32(6):297-301. https://doi.org/10.1111/1755-5922.12093
  29. Roth EM, McKenney JM, Hanotin C, et al. Atorvastatin with or without an antibody to PCSK9 in primary hypercholesterolemia. N Engl J Med. 2012;367(20):1891-900. https://doi.org/10.1056/NEJMoa1201832
  30. McKenney JM, Koren MJ, Kereiakes DJ, et al. Safety and efficacy of a monoclonal antibody to proproteinconvertasesubtilisin/kexin type 9 serine protease, SAR236553/REGN727, in patients with primary hypercholesterolemia receiving ongoing stable atorvastatin therapy. J Am Coll Cardiol. 2012;59(25):2344-2353. https://doi.org/10.1016/j.jacc.2012.03.007
  31. Stein EA, Gipe D, Bergeron J, et al. Effect of a monoclonal antibody to PCSK9, REGN727/SAR236553, to reduce low-density lipoprotein cholesterol in patients with heterozygous familial hypercholesterolaemia on stable statin dose with or without ezetimibe therapy: a phase 2 randomised controlled trial. Lancet. 2012; 380(9836):29-36. https://doi.org/10.1016/S0140-6736(12)60771-5
  32. Teramoto T, Kobayashi M, Uno K, et al. Efficacy and Safety of Alirocumab in Japanese Subjects (Phase 1 and 2 Studies). Am J Cardiol. 2016;118(1):56-63. https://doi.org/10.1016/j.amjcard.2016.04.011
  33. Robinson JG, Farnier M, Krempf M, et al. for the ODYSSEY LONG TERM investigators. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N Engl J Med. 2015;372:1489-1499. https://doi.org/10.1056/NEJMoa1501031
  34. Roth EM, Taskinen MR, Ginsberg HN, et al. Monotherapy with the PCSK9 inhibitor alirocumab versus ezetimibe in patients with hypercholesterolemia: results of a 24 week, double-blind, randomized phase 3 trial. Int J Cardiol. 2014;176(1):55-61. https://doi.org/10.1016/j.ijcard.2014.06.049
  35. Kereiakes DJ, Robinson JG, Cannon CP, et al. Efficacy and safety of the proproteinconvertasesubtilisin/kexin type 9 inhibitor alirocumab among high cardiovascular risk patients on maximally tolerated statin therapy: the ODYSSEY COMBO I study. Am Heart J. 2015;169(6):906-915.e13. https://doi.org/10.1016/j.ahj.2015.03.004
  36. Cannon CP, Cariou B, Blom D, et al. Efficacy and safety of alirocumab in high cardiovascular risk patients with inadequately controlled hypercholesterolaemia on maximally tolerated doses of statins: the ODYSSEY COMBO II randomized controlled trial. Eur Heart J. 2015;36(19):1186-1194. https://doi.org/10.1093/eurheartj/ehv028
  37. Bays H, Gaudet D, Weiss R, et al. Alirocumab as add-on to atorvastatin versus other lipid treatment strategies: ODYSSEY OPTIONS I randomized trial. J Clin Endocrinol Metab. 2015;100(8):3140-3148. https://doi.org/10.1210/jc.2015-1520
  38. Farnier M, Jones P, Severance R, et al. Efficacy and safety of adding alirocumab to rosuvastatin versus adding ezetimibe or doubling the rosuvastatin dose in high cardiovascular-risk patients: the ODYSSEY OPTIONS II randomized trial. Atherosclerosis. 2016; 244:138-146. https://doi.org/10.1016/j.atherosclerosis.2015.11.010
  39. Ginsberg HN, Rader DJ, Raal FJ, et al. Efficacy and safety of alirocumab in patients with severe heterozygous familial hypercholesterolemia. Cardiovasc Drugs Ther. 2016;30(5):473-483. https://doi.org/10.1007/s10557-016-6685-y
  40. Kastelein JJ, Ginsberg HN, Langslet G, et al. ODYSSEY FH I and FH II: 78 week results with alirocumab treatment in 735 patients with heterozygous familial hypercholesterolaemia. Eur Heart J. 2015;36(43):2996-3003. https://doi.org/10.1093/eurheartj/ehv370
  41. Moriarty PM, Thompson PD, Cannon CP, et al. Efficacy and safety of alirocumab versus ezetimibe in statin-intolerant patients, with a statin rechallenge arm: the ODYSSEY ALTERNATIVE randomized trial. J Clin Lipidol. 2015;9(6):758-769. https://doi.org/10.1016/j.jacl.2015.08.006
  42. Kastelein JJ, Robinson JG, Farnier M, et al. Efficacy and safety of alirocumab in patients with heterozygous familial hypercholes- terolemia not adequately controlled with current lipid-lowering therapy: design and rationale of the ODYSSEY FH studies. Cardiovasc Drugs Ther. 2014;28(3):281-9. https://doi.org/10.1007/s10557-014-6523-z
  43. Robinson JG, Colhoun HM, Bays HE, et al. Efficacy and safety of alirocumab as add-on therapy in high-cardiovascular-risk patients with hypercholesterolemia not adequately controlled with atorvastatin (20 or 40 mg) or rosuvastatin (10 or 20 mg): design and rationale of the ODYSSEY OPTIONS Studies. Clin Cardiol. 2014; 37(10):597-604. https://doi.org/10.1002/clc.22327
  44. Stroes E, Guyton JR, Farnier M, et al. for the ODYSSEY CHOICE II investigators. Efficacy and safety of alirocumab 150 mg every 4 weeks in patients with hypercholesterolemia not on statin therapy: the ODYSSEY CHOICE II study. J Am Heart Assoc. 2016; 5(9):e003421. https://doi.org/10.1161/JAHA.116.003421
  45. Schwartz GG, Bessac L, Berdan LG, et al. Effect of alirocumab, a monoclonal anti-body to PCSK9, on long-term cardiovascular outcomes following acute coronary syndromes: rationale and design of the ODYSSEY outcomes trial. Am Heart J. 2014;168:682-689. https://doi.org/10.1016/j.ahj.2014.07.028
  46. Kastelein JJP, Farnier M, Hovingh GK, et al. Efficacy and safety of the PCSK9 monoclonal antibody alirocumab vs placebo in 1254 patients with heterozygous familial hypercholesterolemia (HeFH): analyses up to 78 weeks from four ODYSSEY trials. Presented at European Society of Cardiology Sessions; 2014 Sept; London, UK; abstract. http://congress365.escardio.org/Search-Results?vgnextkeyword=C365PRESENTATION124437#.WbLu2LJJaUk
  47. Hopkins PN, Defesche J, Fouchier SW, et al. Characterization of autosomal dominant hypercholesterolemia caused by PCSK9 gain of function mutations and its specific treatment with alirocumab, a PCSK9 monoclonal antibody. Circ Cardiovasc Genet. 2015; 8(6): 823-831. https://doi.org/10.1161/CIRCGENETICS.115.001129
  48. Moriarty PM, Parhofer KG, Babirak SP, et al. Alirocumab in patients with heterozygous familial hypercholesterolaemia undergoing lipoprotein apheresis: the ODYSSEY ESCAPE trial. Eur Heart J. 2016; 37 (48): 3588-3595. https://doi.org/10.1093/eurheartj/ehw388
  49. Robinson J, Farnier M, Chaudhari U, et al. Adverse events in patients with low-density lipoprotein cholesterol levels <25 or <15 mg/dL on at least two consecutive visits in fourteen randomized, controlled, clinical trials of alirocumab. Presented at American College of Cardiology Sessions; 2015 Mar 17; San Diego, CA; abstract 1164M-05. http://www.athero.org/isa2015/ClinicalBreak/Robinson.pdf
  50. Sabatine MS, Giugliano RP, Wiviott SD, et al. for the open-label study of long-term evaluation against LDL-cholesterol (OSLER) investigators. Efficacy and safety of evolocumab in reducing lipids and cardiovascular events. N Engl J Med. 2015;372:1500-1509. https://doi.org/10.1056/NEJMoa1500858
  51. McDonagh M, Peterson K, Holzhammer B, Fazio S. A Systematic Review of PCSK9 Inhibitors Alirocumab and Evolocumab. J Manag Care Spec Pharm. 2016;22(6):641-653. https://doi.org/10.18553/jmcp.2016.22.6.641
  52. Sabatine MS, Giugliano RP, Keech A, et al. Rationale and design of the Further cardiovascular OUtcomes Research with PCSK9 Inhibition in subjects with Elevated Risk trial. AmHeart J.2016;173:94-101. https://doi.org/10.1016/j.ahj.2015.11.015

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