The experience of using the Russian biosimilar of the original drug eculizumab for the treatment of patients with atypical hemolytic-uremic syndrome

Cover Page


Atypical hemolytic-uremic syndrome (aHUS) is a chronic systemic disease of a genetic nature, which is based on uncontrolled activation of the alternative complement pathway, leading to generalized thrombosis in the vessels of the microvasculature (complement-mediated thrombotic microangiopathy). To date, therapy with eculizumab is the most effective and pathogenetically substantiated method of treating patients with ASH. Using the example of three clinical cases of patients with a verified diagnosis of aHUS, the high efficiency and safety of the world’s first bioanalogue of eculizumab in the treatment of adult patients with aHUS (complement-mediated thrombotic microangiopathy) was demonstrated.

Full Text

Restricted Access

About the authors

Yulia V. Lavrishcheva

Almazov National Medical Research Centre

Author for correspondence.
ORCID iD: 0000-0002-3073-2785

Russian Federation, Moscow


Alexander A. Yakovenko

Pavlov First Saint Petersburg State Medical University

ORCID iD: 0000-0003-1045-9336

Russian Federation, Moscow

канд. мед. наук, доц. каф. нефрологии и диализа

Dmitrii A. Kudlai



Russian Federation, Moscow

д-р мед. наук, ген. дир.


  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



Abstract - 70

PDF (Russian) - 10





  • There are currently no refbacks.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

Address of the Editorial Office:

  • Novij Zykovskij proezd, 3, 40, Moscow, 125167

Correspondence address:

  • Novoslobodskaya str 31c4., Moscow, 127005, Russian Federation

Managing Editor:


© 2018 "Consilium Medicum" Publishing house

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies