contadores web
Skip to main navigation menu Skip to main content Skip to site footer
##common.pageHeaderLogo.altText##

Review article

Vol. 24 No. 2 (2022)

Therapeutic applications of eculizumab

DOI
https://doi.org/10.22267/rus.222402.271
Submitted
April 29, 2021
Published
2022-04-29

Abstract

Introduction: Eculizumab is an IgG type monoclonal antibody designed to treat paroxysmal nocturnal hemoglobinuria (PNH) and its pharmacological target is a member of the complement system. Its mechanism of action has permitted its use in the treatment of orphan diseases such as atypical hemolytic uremic syndrome (aHUS), neuromyelitis optic spectrum disorder (NMOSD), and myasthenia gravis, all of which have a low incidence. Likewise, eculizumab is a viable treatment for Guillain Barré and catastrophic antiphospholipid syndrome (CAS). Objective: To describe the therapeutic applications of eculizumab and its most significant benefits in some illnesses. Materials and methods: A bibliographic search was carried out during the 2010-2021 period in Google Scholar, Science Direct, PubMed y Scielo databases using the keyword eculizumab. Then, the search was refined by using keywords associated with diseases treated with this medication. Results: The mechanism of action of the antibody and its effect on the pathogenesis of paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome, refractory generalized myasthenia gravis, neuromyelitis optic spectrum disorder, catastrophic antiphospholipid syndrome, and Guillain Barré were identified. Conclusions: Eculizumab has high safety and capacity in treating and diminishing symptoms of diverse illnesses, which involve the complement system.

References

  1. Loirat C, Frémeaux-Bacchi V. Atypical hemolytic uremic syndrome. Orphanet J Rare Dis [Internet]. 2011; 6(1):60. DOI: 10.1186/1750-1172-6-60.
  2. Francesc J. Eculizumab: farmacología clínica. Elsevier [Internet]. 2012; 13(2):21–4. Disponible en: https://www.elsevier.es/index.php?p=revista&pRevista=pdf-simple&pii=X0025775312925473&r=4
  3. Dhillon S. Eculizumab: A Review in Generalized Myasthenia Gravis. Drugs [Internet]. 2018; 78(3):367–76. DOI: 10.1007/s40265-018-0875-9.
  4. Brodsky AL. Eculizumab. Hematología [Internet]. 2013; 17(3):276–84. Disponible en: http://www.sah.org.ar/revista/numeros/Vol%2017n3-Eculizumab.pdf
  5. Kindt TJ, Goldsby RA, Osborne BA. Inmunología de Kuby. 6th ed. Mexico: McGraw-Hill; 2014. Disponible en: http://www.fmvz.uat.edu.mx/Libros%20digitales/Inmunologi%CC%81a%20-%20%20Kuby.pdf
  6. Lexicomp. Eculizumab: Drug information [Internet]. UpToDate. 2020 [citado 2020 Sep 23]. Disponible en: https://www.google.com/url?q=https://www-uptodate-com.ezproxy.sibdi.ucr.ac.cr/contents/eculizumab-drug-information?search%3Deculizumab%26source%3Dpanel_search_result%26selectedTitle%3D1~60%26usage_type%3Dpanel%26kp_tab%3Ddrug_general%26display_rank%3D1&sa=D&ust=1601321160529000&usg=AFQjCNGoWySxSZv7JuH3PMRVfJAKRJ-SZA
  7. Cicora F, Roberti J, Mos F, Paz M. Utilización de Eculizumab en un receptor de transplante renal con altos títulos de anticuerpos preformados anti-HLA donante específico. Rev Nefrol Dialisis Transpl [Internet]. 2013 [citado 2022 Mar 22]; 33(2):92-6. Disponible en: https://www.redalyc.org/pdf/5642/564261724005.pdf
  8. Nieto J, Zuluaga M, Bello D. Trasplante renal exitoso con protocolo de eculizumab, timoglobulina, tacrolimus, micofenolato y esteroides en paciente con síndrome hemolítico urémico atípico sin mutación identificada. NefroPlus [Internet]. 2018 [citado 2022 Mar 22]; 10(2):63-7. Disponible en: https://www.revistanefrologia.com/es-trasplante-renal-exitoso-con-protocolo-articulo-X1888970018633870
  9. López M, Morado M, Gaya A, Alonso D, Ojeda E, Muñoz J, et al. Tratamiento de la hemoglobinuria paroxística nocturna con eculizumab: experiencia en España. Med Clin [Internet]. 2011 [citado 2022 Mar 22]; 137(1):8-13. Disponible en: https://www.sciencedirect.com/science/article/abs/pii/S0025775310009991
  10. Comisión Revisora: Sala Especializada de Moléculas nuevas, nuevas Indicaciones y Medicamentos Biológicos. ACTA No. 18 DE 2018 [Internet]. Invima. 2022. Disponible en: https://img.lalr.co/cms/2022/01/28104555/Acta-No.-01-de-2022-SEMNNIMB-Segunda-parte.pdf
  11. Consejo de Salubridad General, Comisión Interinstitucional del Cuadro Básico y Catálogo de Insumos del Sector Salud, Comité Técnico Específico de Medicamentos. Evolución del Proceso del Cuadro Básico y Catálogo de Medicamentos: Período 24-04-2019 al 11-06-19 [Internet]. Mexico: Gobierno de México; 2020 [citado 2021 Mar 9]. Disponible en: http://www.csg.gob.mx/descargas/pdf/priorizacion/cuadro-basico/med/evaluacion-proceso/2019/evo_proc_med_24_04_2019.pdf
  12. Abbas AK, Lichtman AH, Pillai S. Effector Mechanisms of Humoral Immunity: Elimination of Extracellular Microbes and Toxins, Effector Mechanisms of Humoral Immunity: Elimination of Extracellular Microbes and Toxins. En: Basic Immunology: Functions and Disorders of the Immune System [Internet]. 6th ed. Philadelphia (USA): Elsevier; 2020 [citado 2020 Sep 22]. Disponible en: https://iucat.iu.edu/iupuc/17489328
  13. Patriquin CJ, Kuo KHM. Eculizumab and Beyond: The Past, Present, and Future of Complement Therapeutics. Transfus Med Rev [Internet]. 2019; 33(4):256-65. DOI: 10.1016/j.tmrv.2019.09.004.
  14. Teirilä L, Heikkinen-Eloranta J, Kotimaa J, Meri S, Lokki AI. Regulation of the complement system and immunological tolerance in pregnancy. Semin Immunol [Internet]. 2019 Oct 1; 45:101337. DOI: 10.1016/j.smim.2019.101337.
  15. Ricklin D, Barratt-Due A, Mollnes TE. Complement in clinical medicine: Clinical trials, case reports and therapy monitoring. Mol Immunol [Internet]. 2017 Sep 1; 89:10-21. DOI: 10.1016/j.molimm.2017.05.013.
  16. Atkinson JP, Du Clos TW, Mold C, Kulkarni H, Hourcade D, Wu X. 21 - The Human Complement System: Basic Concepts and Clinical Relevance. En: Rich RR, Fleisher TA, Shearer WT, Schroeder HW, Frew AJ, Weyand CM, editores. Clinical Immunology [Internet]. 5th ed. London (UK): Elsevier; 2019 [citado 2020 Sep 20]. Disponible en: http://www.sciencedirect.com/science/article/pii/B9780702068966000211
  17. Cançado RD, Araújo A da S, Sandes AF, Arrais C, Lobo CL de C, Figueiredo MS, et al. Consensus statement for diagnosis and treatment of paroxysmal nocturnal haemoglobinuria. Hematol Transfus Cell Ther [Internet]. 2020 Jul 6 [citado 2020 Sep 21]; 43(3):341-8. Disponible en: http://www.sciencedirect.com/science/article/pii/S2531137920300791
  18. Wijnsma KL, ter Heine R, Moes DJAR, Langemeijer S, Schols SEM, Volokhina EB, et al. Pharmacology, Pharmacokinetics and Pharmacodynamics of Eculizumab, and Possibilities for an Individualized Approach to Eculizumab. Clin Pharmacokinet [Internet]. 2019 Jul 1; 58(7):859-74. DOI: 10.1007/s40262-019-00742-8.
  19. Rosa SH. Monitorización farmacocinética de anticuerpos monoclonales [Tesis de Grado]. España: Universidad de Sevilla; 2016. Disponible en: https://idus.us.es/bitstream/handle/11441/48726/Sonia_Heras_Rosa_TFG.pdf?sequence=1&isAllowed=y
  20. Araya AR. Efecto de la Alteridad de los Aanticuerpos Equinos Sobre la Farmacocinética de los Antivenenos Ofídicos [Tesis de Grado]. Costa Rica: Universidad de Costa Rica; 2011. Disponible en: http://repositorio.sibdi.ucr.ac.cr:8080/jspui/bitstream/123456789/1751/1/33204.pdf
  21. Ryman JT, Meibohm B. Pharmacokinetics of Monoclonal Antibodies. CPT Pharmacomet Syst Pharmacol [Internet]. 2017; 6(9):576-88. DOI: 10.1002/psp4.12224.
  22. Ministerio de Sanidad. FICHA TECNICA SOLIRIS® 300 mg CONCENTRADO PARA SOLUCION PARA PERFUSION [Internet]. Agencia Española de Medicamentos y Productos Sanitarios. 2012 [citado 2020 Sep 28]. Disponible en: https://cima.aemps.es/cima/dochtml/ft/07393001/FT_07393001.html#5-2-propiedades-farmacocin-ticas
  23. Risitano AM, Marotta S. Toward complement inhibition 2.0: Next generation anticomplement agents for paroxysmal nocturnal hemoglobinuria. Am J Hematol [Internet]. 2018; 93(4):564–77. DOI: 10.1002/ajh.25016.
  24. Parker CJ. Update on the diagnosis and management of paroxysmal nocturnal hemoglobinuria. Hematology Am Soc Hematol Educ Program [Internet]. 2016 Dec 2; 2016(1):208–16. DOI: 10.1182/asheducation-2016.1.208.
  25. McKeage K. Eculizumab: a review of its use in paroxysmal nocturnal haemoglobinuria. Drugs [Internet]. 2011 Dec 3; 71(17):2327–45. DOI: 10.2165/11208300-000000000-00000.
  26. Parker CJ, Kar S, Kirkpatrick P. Eculizumab. Nat Rev Drug Discov [Internet]. 2007 Jul 1; 6(7):515–6. DOI: 10.1038/nrd2369.
  27. Kelly RJ, Hill A, Arnold LM, Brooksbank GL, Richards SJ, Cullen M, et al. Long-term treatment with eculizumab in paroxysmal nocturnal hemoglobinuria: sustained efficacy and improved survival. Blood [Internet]. 2011 Jun 23; 117(25):6786–92. DOI: 10.1182/blood-2011-02-333997.
  28. Brodsky RA. Paroxysmal nocturnal hemoglobinuria. Blood [Internet]. 2014 Oct 30; 124(18):2804–11. DOI: 10.1182/blood-2014-02-522128.
  29. Al-Ani F, Chin-Yee I, Lazo-Langner A. Eculizumab in the management of paroxysmal nocturnal hemoglobinuria: patient selection and special considerations. Ther Clin Risk Manag [Internet]. 2016 Aug 1; 12:1161–70. DOI: 10.2147/TCRM.S96720.
  30. García-Rojas VA, Mora-Hernández GA. Hemoglobinuria paroxística nocturna. Revista Médica de Costa Rica y Centroamérica [Internet]. 2016 [citado 2020 Sep 29]; 73(620):659-64. Disponible en: http://revistamedicacr.com/index.php/rmcr/article/view/101
  31. Sridharan M, Go RS, Willrich MAV. Atypical hemolytic uremic syndrome: Review of clinical presentation, diagnosis and management. J Immunol Methods [Internet]. 2018 Oct 1; 461:15–22. DOI: 10.1016/j.jim.2018.07.006.
  32. Legendre CM, Licht C, Muus P, Greenbaum LA, Babu S, Bedrosian C, et al. Terminal complement inhibitor eculizumab in atypical hemolytic-uremic syndrome. N Engl J Med [Internet]. 2013 Jun 6; 368(23):2169–81. DOI: 10.1056/NEJMoa1208981.
  33. Gruppo RA, Rother RP. Eculizumab for congenital atypical hemolytic-uremic syndrome. N Engl J Med [Internet]. 2009 Jan 29; 360(5):544–6. DOI: 10.1056/NEJMc0809959.
  34. Campistol JM, Arias M, Ariceta G, Blasco M, Espinosa M, Grinyó JM, et al. Actualización en síndrome hemolítico urémico atípico: diagnóstico y tratamiento. Documento de consenso. Nefrología [Internet]. 2013 Jan 1; 33(1):27–45. DOI: 10.1016/j.nefro.2015.07.005.
  35. Rondeau E, Cataland SR, Al-Dakkak I, Miller B, Webb NJA, Landau D. Eculizumab Safety: Five-Year Experience From the Global Atypical Hemolytic Uremic Syndrome Registry. Kidney Int Rep [Internet]. 2019 Nov 1; 4(11):1568–76. DOI: 10.1016/j.ekir.2019.07.016.
  36. Wijnsma KL, Duineveld C, Volokhina EB, van den Heuvel LP, van de Kar NCAJ, Wetzels JFM. Safety and effectiveness of restrictive eculizumab treatment in atypical haemolytic uremic syndrome. Nephrol Dial Transplant [Internet]. 2018 Apr 1; 33(4):635–45. DOI: 10.1093/ndt/gfx196.
  37. Covarrubias-San Martín P. Utilización de eculizumab (Soliris®) en pacientes adultos y pediátricos [Tesis de Grado]. Universidad Complutense; 2018. Disponible en: http://147.96.70.122/Web/TFG/TFG/Memoria/PAULINA%20SALOME%20COVARRUBIAS%20SAN%20MARTIN.pdf
  38. Muppidi S, Utsugisawa K, Benatar M, Murai H, Barohn R, Illa I, et al. Long‐term safety and efficacy of eculizumab in generalized myasthenia gravis. Muscle Nerve [Internet]. 2019 [citado 2021 Mar 18]; 60(1):14-24. Disponible en: https://onlinelibrary.wiley.com/doi/full/10.1002/mus.26447
  39. Frampton JE. Eculizumab: A Review in Neuromyelitis Optica Spectrum Disorder. Drugs [Internet]. 2020 May; 80(7):719–27. DOI: 10.1007/s40265-020-01297-w.
  40. Israeli E, Agmon-Levin N, Blank M, Chapman J, Shoenfeld Y. Infections as a Cause of Guillain–Barré Syndrome. En: Infection and Autoimmunity [Internet]. 2nd ed. Elsevier; 2015 [citado 2021 Feb 17]. Disponible en: https://linkinghub.elsevier.com/retrieve/pii/B9780444632692000532
  41. Winer JB. Guillain Barré syndrome. Mol Pathol [Internet]. 2001 Dec; 54(6):381-5. Disponible en: https://pubmed.ncbi.nlm.nih.gov/11724912/
  42. de la O-Peña D, Robles-Figueroa M, Chávez-Peña Q, Bedolla-Barajas M. Características del síndrome de Guillain-Barré en adultos: resultados de un hospital universitario. Rev Med Inst Mex Seguro Soc [Internet]. 2015; 53(6):678-85. Disponible en: https://www.medigraphic.com/pdfs/imss/im-2015/im156c.pdf
  43. Berciano J. Axonal pathology in early stages of Guillain-Barré syndrome. Neurología (English Edition) [Internet]. 2020 Aug 20 [citado 2021 Feb 18]. Disponible en: https://www.sciencedirect.com/science/article/pii/S2173580820301553
  44. Frey SL, Lee KYC. Number of Sialic Acid Residues in Ganglioside Headgroup Affects Interactions with Neighboring Lipids. Biophys J [Internet]. 2013 Sep 17; 105(6):1421-31. DOI: 10.1016/j.bpj.2013.07.051.
  45. Misawa S, Kuwabara S, Sato Y, Yamaguchi N, Nagashima K, Katayama K, et al. Safety and efficacy of eculizumab in Guillain-Barré syndrome: a multicentre, double-blind, randomised phase 2 trial. Lancet Neurol [Internet]. 2018 Jun 1; 17(6):519-29. DOI: 10.1016/S1474-4422(18)30114-5.
  46. Garcia-Carrasco M, Mendoza-Pinto C, Macias-Diaz S, Vazquez de Lara F, Etchegaray-Morales I, Galvez-Romero JL, et al. The role of infectious diseases in the catastrophic antiphospholipid syndrome. Autoimmun Rev [Internet]. 2015 Nov 1; 14(11):1066-71. DOI: 10.1016/j.autrev.2015.07.009.
  47. Guerra N, Zuniga M, Lopez J, Arenas L, Garcia J. Catastrophic antiphospholipid syndrome. Acta Colomb Cuid Intensivo [Internet]. 2019 Jun 26; 19(3):154-9. Disponible en: https://www.sciencedirect.com/science/article/abs/pii/S0122726219300205?via%3Dihub
  48. Sierra Merlano RM, Rocha Reyes E, Moreno Grau Á. Síndrome antifosfolípido catastrófico (síndrome de asherson): presentación de un caso probable. Rev Cienc Bioméd [Internet]. 2020 Nov 19; 7(1):112-6. Disponible en: https://dialnet.unirioja.es/servlet/articulo?codigo=7648235
  49. Kazzaz NM, McCune WJ, Knight JS. Treatment of catastrophic antiphospholipid syndrome. Curr Opin Rheumatol [Internet]. 2016 May; 28(3):218-27. DOI: 10.1097/BOR.0000000000000269.
  50. Ignasi P, Ricard C. Síndrome Antifosfolliídico Catastrófico. Rev Fac Cienc Méd Univ Cuenca [Internet]. 2016 Dec; 34(3):76-87. Disponible en: https://publicaciones.ucuenca.edu.ec/ojs/index.php/medicina/article/view/1231
  51. Tinti MG, Carnevale V, Inglese M, Molinaro F, Bernal M, Migliore A, et al. Eculizumab in refractory catastrophic antiphospholipid syndrome: a case report and systematic review of the literature. Clin Exp Med [Internet]. 2019 Aug; 19(3):281-8. DOI: 10.1007/s10238-019-00565-8.
  52. Yelnik CM, Miranda S, Mékinian A, Lazaro E, Quéméneur T, Provot F, et al. Patients with refractory catastrophic antiphospholipid syndrome respond inconsistently to eculizumab. Blood [Internet]. 2020 Nov 19; 136(21):2473-7. DOI: 10.1182/blood.2020007499.
  53. Zhang R, Zhou M, Qi J, Miao W, Zhang Z, Depei W, et al. Efficacy and Safety of Eculizumab in the Treatment of Transplant-Associated Thrombotic Microangiopathy: A Systematic Review and Meta-A nalysis. Front Immunol [Internet]. 2021 [citado 2021 Mar 18]; 11. Disponible en: https://www.frontiersin.org/articles/10.3389/fimmu.2020.564647/full
  54. Marks WH, Mamode N, Montgomery RA, Stegall MD, Ratner LE, Cornell LD, et al. Safety and efficacy of eculizumab in the prevention of antibody-mediated rejection in living-donor kidney transplant recipients requiring desensitization therapy: A randomized trial. Am J Transplant [Internet]. 2019; 19(10):2876–88. DOI: 10.1111/ajt.15364.
  55. Saborío IE, Durán M, Villalobos D. Síndrome urémico hemolítico en pediatría. Rev Méd Sinerg [Internet]. 2019; 4(4):55–66. Disponible en: https://revistamedicasinergia.com/index.php/rms/article/view/208
  56. Glassman A. A $400,000 Drug and Why It Matters for Global Health. Center For Global Development. [acualizado 2012 Sep 25, citado 2022 Mar 24]. Disponible en: https://www.cgdev.org/blog/400000-drug-and-why-it-matters-global-health

Downloads

Download data is not yet available.