Опыт применения российского биоаналога оригинального препарата экулизумаба для лечения больных атипичным гемолитико-уремическим синдромом

1. Yoshida Y, Kato H, Ikeda Y, Nangaku M. Pathogenesis of Atypical Hemolytic Uremic Syndrome. J Atheroscler Thromb. 2019;26(2):99-110. doi: 10.5551/jat.RV17026
2. Schramm EC, Roumenina LT, Rybkine T, et al. Mapping interactions between complement C3 and regulators using mutations in atypical hemolytic uremic syndrome. Blood. 2015;125:2359-69. doi: 10.1182/blood-2014-10-609073
3. Frimat M, Tabarin F, Dimitrov JD, et al. Complement activation by heme as a secondary hit for atypical hemolytic uremic syndrome. Blood. 2013;122:282-92. doi: 10.1182/ blood-2013-03-489245
4. Marinozzi MC, Vergoz L, Rybkine T, et al. Complement factor B mutations in atypical hemolytic uremic syndrome-diseaserelevant or benign? J Am Soc Nephrol. 2014; 25:2053-65. doi: 10.1681/ASN.2013070796
5. Bernabeu-Herrero ME, Jimenez-Alcazar M, Anter J, et al. Complement factor H, FHR-3 and FHR-1 variants associate in an extended haplotype conferring increased risk of atypical hemolytic uremic syndrome. Mol Immunol. 2015;67:276-86. doi: 10.1016/j.molimm.2015.06.021
6. Raina R, Krishnappa V, Blaha T, et al. Atypical Hemolytic-Uremic Syndrome: An Update on Pathophysiology, Diagnosis, and Treatment. Ther Apher Dial. 2019;23(1):4-21. doi: 10.1111/1744-9987.12763
7. Sansbury FH, Cordell HJ, Bingham C, et al. Factors determining penetrance in familial atypical haemolytic uraemic syndrome. J Med Genet. 2014;51:756-64. doi: 10.1136/jmedgenet-2014-102498
8. Bresin E, Rurali E, Caprioli J, et al. Combined complement gene mutations in atypical hemolytic uremic syndrome influence clinical phenotype. J Am Soc Nephrol. 2013;24:475-86. doi: 10.1681/ASN.2012090884
9. Fremeaux-Bacchi V, Fakhouri F, Garnier A, et al. Genetics and outcome of atypical hemolytic uremic syndrome: a nationwide French series comparing children and adults. Clin J Am Soc Nephrol. 2013;8:554-62. doi: 10.2215/CJN.04760512
10. Couzi L, Contin-Bordes C, Marliot F, et al. Inherited deficiency of membrane cofactor protein expression and varying manifestations of recurrent atypical hemolytic uremic syndrome in a sibling pair. Am J Kidney Dis. 2008;52(2):e5-9. doi: 10.1053/j.ajkd.2008.02.359
11. Almalki AH, Sadagah LF, Qureshi M, et al. Atypical hemolytic-uremic syndrome due to complement factor I mutation. World J Nephrol. 2017;6(6):243-50. doi: 10.5527/wjn.v6.i6.243
12. Zhang K, Lu Y, Harley KT, Tran MH. Atypical Hemolytic Uremic Syndrome: A Brief Review. Hematol Rep. 2017;9(2):7053. doi: 10.4081/hr.2017.7053
13. Sridharan M, Go RS, Willrich MAV. Atypical hemolytic uremic syndrome: Review of clinical presentation, diagnosis and management. J Immunol Methods. 2018;461:15-22. doi: 10.1016/j.jim.2018.07.006
14. Knoop M, Haller H, Menne J. Human genetics in atypical hemolytic uremic syndrome-its role in diagnosis and treatment. Internist (Berl). 2018;59(8):799-804. doi: 10.1007/s00108-018-0455-9
15. Smith-Jackson K, Yang Y, Denton H, et al. Hyperfunctional complement C3 promotes C5-dependent atypical hemolytic uremic syndrome in mice. J Clin Invest. 2019;12(3):1061-75. doi: 10.1172/JCI99296
16. Loirat C, Frémeaux-Bacchi V. Atypical hemolytic uremic syndrome. Orphanet J Rare Dis. 2011;6:60. doi: 10.1186/1750-1172-6-60
17. Fakhouri F, Zuber J, Frémeaux-Bacchi V, Loirat C. Haemolytic uraemic syndrome. Lancet. 2017;390(10095):681-96. doi: 10.1016/S0140-6736(17)30062-4
18. Rieger M, Mannucci PM, Kremer Hovinga JA, et al. ADAMTS13 autoantibodies in patients with thrombotic microangiopathies and other immunomediated diseases. Blood. 2005;106(4):1262-7. doi: 10.1182/blood-2004-11-4490
19. Sepúlveda RA, Tagle R, Jara A. Atypical hemolytic uremic syndrome. Rev Med Chil. 2018;146(6):770-9. doi: 10.4067/s0034-98872018000600770
20. Waters AM, Licht C. aHUS caused by complement dysregulation: new therapies on the horizon. Pediatr Nephrol. 2011;26(1):41-57. 
doi: 10.1007/s00467-010-1556-4
21. Wijnsma KL, Duineveld C, Wetzels JFM, van de Kar NCAJ. Eculizumab in atypical hemolytic uremic syndrome: strategies toward restrictive use. Pediatr Nephrol. 2019;34(11):2261-77. doi: 10.1007/s00467-018-4091-3
22. Fakhouri F, Hourmant M, Campistol JM, et al.  Terminal Complement Inhibitor Eculizumab in Adult Patients With Atypical Hemolytic Uremic Syndrome: A Single-Arm, Open-Label Trial. Am J Kidney Dis. 2016;68(1):84-93. doi: 10.1053/j.ajkd.2015.12.034
23. Kato H, Miyakawa Y, Hidaka Y, et al. Safety and effectiveness of eculizumab for adult patients with atypical hemolytic-uremic syndrome in Japan: interim analysis of post-marketing surveillance. Clin Exp Nephrol. 2019;23(1):65-75. doi: 10.1007/s10157-018-1609-8
24. Ito S, Hidaka Y, Inoue N, et al. Safety and effectiveness of eculizumab for pediatric patients with atypical hemolytic-uremic syndrome in Japan: interim analysis of post-marketing surveillance. Clin Exp Nephrol. 2019;23(1):112-21. doi: 10.1007/s10157-018-1610-2
25. Olson SR, Lu E, Sulpizio E, et al. When to Stop Eculizumab in Complement-Mediated Thrombotic Microangiopathies. Am J Nephrol. 2018;48(2):96-107. doi: 10.1159/000492033
26. Иванов Р., Секарева Г., Кравцова О. и др. Правила проведения исследований биоаналоговых лекарственных средств (биоаналогов). Фармакокинетика и фармакодинамика. 2014;1:21-36 [Ivanov R, Sekareva G, Kravcova O, et al. Pravila provedenija issledovanij bioanalogovyh lekarstvennyh sredstv (bioanalogov). Farmakokinetika i farmakodinamika. 2014;1:21-36 (In Russ.)].
27. Kulagin A, Ptushkin V, Lukina E, et al. Phase III clinical trial of Elizaria® and Soliris® in adult patients with paroxysmal nocturnal hemoglobinuria: results of comparative analysis of efficacy, safety, and pharmacological data. Blood. 2019;134(Suppl. 1):3748. doi: 10.1182/blood-2019-125693
28. Эмирова Х.М., Орлова О.М., Музуров А.Л. и др. Применения Элизарии® при атипичном гемолитико-уремическом синдроме. Педиатрия. 2019;98(5):225-9 [Jemirova HM, Orlova OM, Muzurov AL, 
et al. Primenenija Elizarii® pri atipichnom gemolitiko-uremicheskom sindrome. Pediatrija. 2019;98(5):225-9 (In Russ.)].
29. Lavrishcheva IV, Jakovenko AA, Kudlay DA. A case report of atypical hemolytic-uremic syndrome treatment with the first Russian eculizumab in adult patient. Urology & Nephrology Open Access Journal. 2020;8(2):37-40.
30. Goodship TH, Cook HT, Fakhouri F, et al.: Atypical hemolytic uremic syndrome and C3 glomerulopathy: conclusions from a kidney disease: improving global outcomes (KDIGO) controversies conference. Kidney Int. 2017;91:539-51. doi: 10.1016/j.kint.2016.10.005 
31. Loirat C, Fakhouri F, Ariceta G, et al. An international consensus approach to the management of atypical hemolytic uremic syndrome in children. Pediatr Nephrol. 2016;31:15-39.
32. Wong EKS, Goodship THJ, Kavanagh D. Complement therapy in atypical haemolytic uraemic syndrome (aHUS). Molecular Immunology. 2013;56(3):199-212.
33. Legendre CM, Licht C, Muus P, et al. Terminal complement inhibitor eculizumab in atypical hemolytic-uremic syndrome. N Engl J Med. 2013;368:2169-81. 
34. Licht C, Greenbaum LA, Muus P, et al. Efficacy and safety of eculizumab in atypical hemolytic uremic syndrome from 2-year extensions of phase 2 studies. Kidney Int. 2015;87:1061-73.
35. Emirova K, Volokhina E, Tolstova E, van den Heuvel B. Recovery of renal function after long-term dialysis and resolution of cardiomyopathy in a patient with aHUS receiving eculizumab. BMJ Case Rep. 2016;2016. pii: bcr2015213928. doi: 10.1136/bcr-2015-213928

________________________________________________

1. Yoshida Y, Kato H, Ikeda Y, Nangaku M. Pathogenesis of Atypical Hemolytic Uremic Syndrome. J Atheroscler Thromb. 2019;26(2):99-110. doi: 10.5551/jat.RV17026
2. Schramm EC, Roumenina LT, Rybkine T, et al. Mapping interactions between complement C3 and regulators using mutations in atypical hemolytic uremic syndrome. Blood. 2015;125:2359-69. doi: 10.1182/blood-2014-10-609073
3. Frimat M, Tabarin F, Dimitrov JD, et al. Complement activation by heme as a secondary hit for atypical hemolytic uremic syndrome. Blood. 2013;122:282-92. doi: 10.1182/ blood-2013-03-489245
4. Marinozzi MC, Vergoz L, Rybkine T, et al. Complement factor B mutations in atypical hemolytic uremic syndrome-diseaserelevant or benign? J Am Soc Nephrol. 2014; 25:2053-65. doi: 10.1681/ASN.2013070796
5. Bernabeu-Herrero ME, Jimenez-Alcazar M, Anter J, et al. Complement factor H, FHR-3 and FHR-1 variants associate in an extended haplotype conferring increased risk of atypical hemolytic uremic syndrome. Mol Immunol. 2015;67:276-86. doi: 10.1016/j.molimm.2015.06.021
6. Raina R, Krishnappa V, Blaha T, et al. Atypical Hemolytic-Uremic Syndrome: An Update on Pathophysiology, Diagnosis, and Treatment. Ther Apher Dial. 2019;23(1):4-21. doi: 10.1111/1744-9987.12763
7. Sansbury FH, Cordell HJ, Bingham C, et al. Factors determining penetrance in familial atypical haemolytic uraemic syndrome. J Med Genet. 2014;51:756-64. doi: 10.1136/jmedgenet-2014-102498
8. Bresin E, Rurali E, Caprioli J, et al. Combined complement gene mutations in atypical hemolytic uremic syndrome influence clinical phenotype. J Am Soc Nephrol. 2013;24:475-86. doi: 10.1681/ASN.2012090884
9. Fremeaux-Bacchi V, Fakhouri F, Garnier A, et al. Genetics and outcome of atypical hemolytic uremic syndrome: a nationwide French series comparing children and adults. Clin J Am Soc Nephrol. 2013;8:554-62. doi: 10.2215/CJN.04760512
10. Couzi L, Contin-Bordes C, Marliot F, et al. Inherited deficiency of membrane cofactor protein expression and varying manifestations of recurrent atypical hemolytic uremic syndrome in a sibling pair. Am J Kidney Dis. 2008;52(2):e5-9. doi: 10.1053/j.ajkd.2008.02.359
11. Almalki AH, Sadagah LF, Qureshi M, et al. Atypical hemolytic-uremic syndrome due to complement factor I mutation. World J Nephrol. 2017;6(6):243-50. doi: 10.5527/wjn.v6.i6.243
12. Zhang K, Lu Y, Harley KT, Tran MH. Atypical Hemolytic Uremic Syndrome: A Brief Review. Hematol Rep. 2017;9(2):7053. doi: 10.4081/hr.2017.7053
13. Sridharan M, Go RS, Willrich MAV. Atypical hemolytic uremic syndrome: Review of clinical presentation, diagnosis and management. J Immunol Methods. 2018;461:15-22. doi: 10.1016/j.jim.2018.07.006
14. Knoop M, Haller H, Menne J. Human genetics in atypical hemolytic uremic syndrome-its role in diagnosis and treatment. Internist (Berl). 2018;59(8):799-804. doi: 10.1007/s00108-018-0455-9
15. Smith-Jackson K, Yang Y, Denton H, et al. Hyperfunctional complement C3 promotes C5-dependent atypical hemolytic uremic syndrome in mice. J Clin Invest. 2019;12(3):1061-75. doi: 10.1172/JCI99296
16. Loirat C, Frémeaux-Bacchi V. Atypical hemolytic uremic syndrome. Orphanet J Rare Dis. 2011;6:60. doi: 10.1186/1750-1172-6-60
17. Fakhouri F, Zuber J, Frémeaux-Bacchi V, Loirat C. Haemolytic uraemic syndrome. Lancet. 2017;390(10095):681-96. doi: 10.1016/S0140-6736(17)30062-4
18. Rieger M, Mannucci PM, Kremer Hovinga JA, et al. ADAMTS13 autoantibodies in patients with thrombotic microangiopathies and other immunomediated diseases. Blood. 2005;106(4):1262-7. doi: 10.1182/blood-2004-11-4490
19. Sepúlveda RA, Tagle R, Jara A. Atypical hemolytic uremic syndrome. Rev Med Chil. 2018;146(6):770-9. doi: 10.4067/s0034-98872018000600770
20. Waters AM, Licht C. aHUS caused by complement dysregulation: new therapies on the horizon. Pediatr Nephrol. 2011;26(1):41-57. 
doi: 10.1007/s00467-010-1556-4
21. Wijnsma KL, Duineveld C, Wetzels JFM, van de Kar NCAJ. Eculizumab in atypical hemolytic uremic syndrome: strategies toward restrictive use. Pediatr Nephrol. 2019;34(11):2261-77. doi: 10.1007/s00467-018-4091-3
22. Fakhouri F, Hourmant M, Campistol JM, et al.  Terminal Complement Inhibitor Eculizumab in Adult Patients With Atypical Hemolytic Uremic Syndrome: A Single-Arm, Open-Label Trial. Am J Kidney Dis. 2016;68(1):84-93. doi: 10.1053/j.ajkd.2015.12.034
23. Kato H, Miyakawa Y, Hidaka Y, et al. Safety and effectiveness of eculizumab for adult patients with atypical hemolytic-uremic syndrome in Japan: interim analysis of post-marketing surveillance. Clin Exp Nephrol. 2019;23(1):65-75. doi: 10.1007/s10157-018-1609-8
24. Ito S, Hidaka Y, Inoue N, et al. Safety and effectiveness of eculizumab for pediatric patients with atypical hemolytic-uremic syndrome in Japan: interim analysis of post-marketing surveillance. Clin Exp Nephrol. 2019;23(1):112-21. doi: 10.1007/s10157-018-1610-2
25. Olson SR, Lu E, Sulpizio E, et al. When to Stop Eculizumab in Complement-Mediated Thrombotic Microangiopathies. Am J Nephrol. 2018;48(2):96-107. doi: 10.1159/000492033
26. Иванов Р., Секарева Г., Кравцова О. и др. Правила проведения исследований биоаналоговых лекарственных средств (биоаналогов). Фармакокинетика и фармакодинамика. 2014;1:21-36 [Ivanov R, Sekareva G, Kravcova O, et al. Pravila provedenija issledovanij bioanalogovyh lekarstvennyh sredstv (bioanalogov). Farmakokinetika i farmakodinamika. 2014;1:21-36 (In Russ.)].
27. Kulagin A, Ptushkin V, Lukina E, et al. Phase III clinical trial of Elizaria® and Soliris® in adult patients with paroxysmal nocturnal hemoglobinuria: results of comparative analysis of efficacy, safety, and pharmacological data. Blood. 2019;134(Suppl. 1):3748. doi: 10.1182/blood-2019-125693
28. Эмирова Х.М., Орлова О.М., Музуров А.Л. и др. Применения Элизарии® при атипичном гемолитико-уремическом синдроме. Педиатрия. 2019;98(5):225-9 [Jemirova HM, Orlova OM, Muzurov AL, 
et al. Primenenija Elizarii® pri atipichnom gemolitiko-uremicheskom sindrome. Pediatrija. 2019;98(5):225-9 (In Russ.)].
29. Lavrishcheva IV, Jakovenko AA, Kudlay DA. A case report of atypical hemolytic-uremic syndrome treatment with the first Russian eculizumab in adult patient. Urology & Nephrology Open Access Journal. 2020;8(2):37-40.
30. Goodship TH, Cook HT, Fakhouri F, et al.: Atypical hemolytic uremic syndrome and C3 glomerulopathy: conclusions from a kidney disease: improving global outcomes (KDIGO) controversies conference. Kidney Int. 2017;91:539-51. doi: 10.1016/j.kint.2016.10.005 
31. Loirat C, Fakhouri F, Ariceta G, et al. An international consensus approach to the management of atypical hemolytic uremic syndrome in children. Pediatr Nephrol. 2016;31:15-39.
32. Wong EKS, Goodship THJ, Kavanagh D. Complement therapy in atypical haemolytic uraemic syndrome (aHUS). Molecular Immunology. 2013;56(3):199-212.
33. Legendre CM, Licht C, Muus P, et al. Terminal complement inhibitor eculizumab in atypical hemolytic-uremic syndrome. N Engl J Med. 2013;368:2169-81. 
34. Licht C, Greenbaum LA, Muus P, et al. Efficacy and safety of eculizumab in atypical hemolytic uremic syndrome from 2-year extensions of phase 2 studies. Kidney Int. 2015;87:1061-73.
35. Emirova K, Volokhina E, Tolstova E, van den Heuvel B. Recovery of renal function after long-term dialysis and resolution of cardiomyopathy in a patient with aHUS receiving eculizumab. BMJ Case Rep. 2016;2016. pii: bcr2015213928. doi: 10.1136/bcr-2015-213928

Ю.В. Лаврищева1, А.А. Яковенко2, Д.А. Кудлай3

1ФГБУ «Национальный медицинский исследовательский центр им. В.А. Алмазова» Минздрава России, Санкт-Петербург;
2ФГБОУ ВО «Первый Санкт-Петербургский государственный медицинский университет им. акад. И.П. Павлова» Минздрава России, Санкт-Петербург, Россия;
3АО «Генериум», Москва, Россия

Исследование выполнено на базе ФГБУ «НМИЦ им. В.А. Алмазова».

________________________________________________

Iu.V. Lavrishcheva1, A.A. Jakovenko2, D.A. Kudlay3

1 Almazov National Medical Research Centre, Saint Petersburg, Russia;
2 Pavlov First Saint Petersburg State Medical University, Saint Petersburg, Russia;
3 JSC GENERIUM, Moscow, Russia