Uso de eculizumab en el tratamiento de microangiopatía trombótica: Revisión sistemática y metaanálisis
| dc.contributor.advisor | Porras, Alexandra | |
| dc.contributor.advisor | Rico, Alejandro | |
| dc.contributor.author | Leon Chavez, Angel Fabian | |
| dc.contributor.orcid | 0009-0003-1994-639X | |
| dc.date.accessioned | 2025-07-16T13:17:26Z | |
| dc.date.available | 2025-07-16T13:17:26Z | |
| dc.date.issued | 2025-05 | |
| dc.description.abstract | Introducción: Las microangiopatías trombóticas (MAT) comprenden un grupo heterogéneo de trastornos caracterizados por daño endotelial microvascular, lo que requiere una clasificación precisa para un diagnóstico y manejo óptimos. Las MAT incluyen formas hereditarias como la púrpura trombocitopénica trombótica (PTT) y el síndrome urémico hemolítico atípico (SHUa), así como MAT secundarias asociadas a condiciones como embarazo, trasplante de órganos e infecciones. El SHU mediado por toxina Shiga, especialmente prevalente en niños, suele provocar lesión renal aguda. Las opciones terapéuticas incluyen la plasmaféresis y los inhibidores del complemento, destacando eculizumab por su eficacia en MAT mediadas por el complemento. Métodos Se realizó una revisión sistemática siguiendo las directrices PRISMA para evaluar la eficacia de eculizumab en el manejo de las MAT. Se incluyeron revisiones sistemáticas publicadas entre 2019 y 2024, conforme a las recomendaciones de JAMA. Los datos se sintetizaron utilizando el software Jamovi y el modelo de efectos aleatorios DerSimonian-Laird para el metaanálisis. Resultados De 5,349 artículos identificados en PubMed, Embase y LILACS, 12 revisiones sistemáticas cumplieron los criterios de inclusión, abarcando en conjunto 264 artículos que evaluaron eculizumab en MAT. El SHUa fue abordado en el 33.3% de las revisiones, con un subconjunto significativo enfocado en MAT asociadas al embarazo. Las MAT asociadas a trasplante estuvieron presentes en el 41.7% de los estudios. El riesgo de sesgo, evaluado mediante ROBIS, estuvo presente en el 50% de los estudios incluidos. La mortalidad agrupada fue extremadamente baja (4.69e-5, I² = 0%), con tasas de complicaciones igualmente bajas (8.41e-5, I² = 0%) en nueve estudios. La pérdida de injerto por MAT asociada a trasplante se reportó en 2.48e-4 (I² = 0%). Eculizumab demostró resultados superiores, con una razón de momios para mortalidad de 0.16 (log OR = -1.82, IC 95% [-3.22, -0.41], I² = 89.1%), subrayando su eficacia frente a otras terapias. Conclusión: Eculizumab se posiciona como una de las principales opciones terapéuticas para las MAT, reduciendo significativamente la mortalidad, la morbilidad y la pérdida de injerto, especialmente en casos asociados a trasplante. Para validar aún más estos hallazgos y reducir el sesgo, se requieren ensayos clínicos aleatorizados bien diseñados que aborden etiologías específicas de MAT. Estos estudios permitirán refinar los protocolos de tratamiento y mejorar los resultados en esta compleja entidad clínica. | |
| dc.description.abstractenglish | Introduction: Thrombotic microangiopathies (TMAs) are a heterogeneous group of disorders characterized by microvascular endothelial damage, necessitating precise classification for optimal diagnosis and treatment. This encompasses hereditary forms like thrombotic thrombocytopenic purpura (TTP) and atypical hemolytic uremic syndrome (aHUS), alongside secondary TMAs related to external conditions such as pregnancy, organ transplantation, and infections. Notably, Shiga toxin-mediated HUS is prevalent in children, often causing acute kidney injury. Treatments include plasmapheresis and complement inhibitors like eculizumab, which is particularly effective for complement-mediated TMAs. Methods: A systematic review adhering to PRISMA guidelines assessed the efficacy of eculizumab in treating TMAs. Systematic reviews published between 2019 and 2024 were included based on JAMA guidelines, culminating in a meta-analysis using Jamovi software and the Der Simonian Laird method. Results: Out of 5349 articles from PubMed, Embase, and LILACS, 12 met the inclusion criteria. These reviews incorporated 264 articles overall, scrutinizing Eculizumab's effect on TMAs. Atypical HUS was addressed in 33.34%, with a notable focus on pregnancy-associated cases. Transplant-associated TMAs featured in 41.67% of studies. Risk of bias, assessed with ROBIS, reflected a 50% rate across studies. Pooled mortality was extremely low (4.69e-5, I2 = 0%), with complication rates (8.41e-5, I2 = 0%) evaluated in nine studies. Graft loss due to transplant-associated TMAs showed a rate of 2.48e-4 (I2 = 0%). Eculizumab was superior with a mortality odds ratio of 0.16 (log OR = -1.82, 95% CI [-3.22, -0.41], I2 = 89.08), emphasizing its efficacy over other treatments. Conclusion: Eculizumab emerges as a leading therapeutic option for TMAs, significantly reducing mortality, morbidity, and graft loss, particularly in transplant-associated scenarios. To diminish biases and substantiate these findings, targeted randomized clinical trials are recommended to explore specific TMA aetiologies, thereby refining treatment protocols and enhancing healthcare delivery. | |
| dc.description.degreelevel | Maestría | spa |
| dc.description.degreename | Magíster en Epidemiología | spa |
| dc.description.sponsorship | Universidad El Bosque | |
| dc.format.mimetype | application/pdf | |
| dc.identifier.instname | instname:Universidad El Bosque | spa |
| dc.identifier.reponame | reponame:Repositorio Institucional Universidad El Bosque | spa |
| dc.identifier.repourl | repourl:https://repositorio.unbosque.edu.co | |
| dc.identifier.uri | https://hdl.handle.net/20.500.12495/14967 | |
| dc.language.iso | en | |
| dc.language.iso | es | |
| dc.publisher.faculty | Facultad de Medicina | spa |
| dc.publisher.grantor | Universidad El Bosque | spa |
| dc.publisher.program | Maestría en Epidemiología | spa |
| dc.relation.references | 1. Noris M, Ruggenenti PL, Remuzzi G. Thrombotic Microangiopathies, Including Hemolytic Uremic Syndrome. In: Johnson Richard, Floege Jurgen, Tonelli Marcello, editors. Comprehensive Clinical Nephrology. Seventh. Philadelphia; 2024. p. 350–62. | |
| dc.relation.references | 2. Manglani M, Kini P. Thrombotic microangiopathy in children: Redefining hemolytic uremic syndrome, thrombotic thrombocytopenic purpura and related disorders. Pediatric Hematology Oncology Journal. 2024 Mar 1;9(1):45–53. | |
| dc.relation.references | 3. Mele C, Noris M, Remuzzi G. Hemolytic Uremic Syndrome. In: Ronco Claudio, Bellomo Rinaldo, editors. Critical Care Nephrology by Claudio Ronco, Rinaldo Bellomo, John A Kellum y Zaccaria Ricci. Third edition. Barcelona; 2020. p. 294–301. | |
| dc.relation.references | 4. Kavanagh D, Sheerin Neil. Thrombotic Microangiopathies. In: Yu Alan, Chertow Glenn, Luyckx Valerie, Marsden Philip, Skorecki Karl, Taal Maarten, editors. Brenner and Rector’s The Kidney [Internet]. 11th ed. Barcelona; 2021. Available from: http://www.atypicalhus.co.uk/. | |
| dc.relation.references | 5. Vivarelli M, Thurman JM. Complement-Mediated Glomerulonephritis and Thrombotic Microangiopathy. In: Scott Gilbert, editor. National Kidney Foundation Primer on Kidney Diseases. Eighth. Philadelphia; 2023. p. 222–33. | |
| dc.relation.references | 6. Cugno M, Capone V, Griffini S, Grovetti E, Pintarelli G, Porcaro L, et al. Eculizumab treatment in atypical hemolytic uremic syndrome: correlation between functional complement tests and drug levels. J Nephrol. 2022 May 1;35(4):1205–11. | |
| dc.relation.references | 7. Parra AP, Ramos N, Perurena-Prieto J. Pharmacokinetics of eculizumab in adult and pediatric patients with atypical hemo-lytic uremic syndrome and C3 glomerulopathy-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Farmacia Hospitalaria. 2024;48:16–22. | |
| dc.relation.references | 8. Antonucci L, Thurman JM, Vivarelli M. Complement inhibitors in pediatric kidney diseases: new therapeutic opportunities. Pediatric Nephrology. 2024 May 1;39(5):1387–404. | |
| dc.relation.references | 9. 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. 2019 Jul 1;58(7):859–74. | |
| dc.relation.references | 10. Le Tilly O, Gatault P, Semlali S, Sberro-Soussan R, Passot C, Bertrand D, et al. Eculizumab dose tapering should take into account the nonlinearity of its pharmacokinetics. Br J Clin Pharmacol. 2024; | |
| dc.relation.references | 11. Peffault de Latour R, Brodsky RA, Ortiz S, Risitano AM, Jang JH, Hillmen P, et al. Pharmacokinetic and pharmacodynamic effects of ravulizumab and eculizumab on complement component 5 in adults with paroxysmal nocturnal haemoglobinuria: results of two phase 3 randomised, multicentre studies. Br J Haematol. 2020 Nov 1;191(3):476–85. | |
| dc.relation.references | 12. Ter Avest M, Bouwmeester RN, Duineveld C, Wijnsma KL, Volokhina EB, Van Den Heuvel LPWJ, et al. Proposal for individualized dosing of eculizumab in atypical haemolytic uraemic syndrome: patient friendly and cost-effective. Nephrology Dialysis Transplantation. 2023 Feb 1;38(2):362–71. | |
| dc.relation.references | 13. Urrútia G, Bonfill1 X. EDITORIAL LA DECLARACIÓN PRISMA: UN PASO ADELANTE EN LA MEJORA DE LAS PUBLICACIONES DE LA REVISTA ESPAÑOLA DE SALUD PÚBLICA [Internet]. Available from: http://www.prisma | |
| dc.relation.references | 14. Moher D, Liberati A, Tetzlaff J, Altman DG, Antes G, Atkins D, et al. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. Vol. 6, PLoS Medicine. Public Library of Science; 2009. | |
| dc.relation.references | 15. Santamaría Olmo R, Santamaría R. NefroPlus 2017;9(1):100-101 [Internet]. Vol. 9. Available from: http://www.redcaspe.org/ | |
| dc.relation.references | 16. Whiting P, Savović J, Higgins JPT, Caldwell DM, Reeves BC, Shea B, et al. ROBIS: A new tool to assess risk of bias in systematic reviews was developed. J Clin Epidemiol. 2016 Jan 1;69:225–34. | |
| dc.relation.references | 17. Herramientas ROBINS para evaluar el riesgo de sesgo de estudios no aleatorizados [Internet]. 2022. Available from: www.evidencia.org.ar | |
| dc.relation.references | 18. Suarez MLG, Thongprayoon C, Mao MA, Leeaphorn N, Bathini T, Cheungpasitporn W. Outcomes of kidney transplant patients with atypical hemolytic uremic syndrome treated with eculizumab: A systematic review and meta-analysis. J Clin Med. 2019 Jul 1;8(7). | |
| dc.relation.references | 19. Tang ZC, Hui H, Shi C, Chen X. New findings in preventing recurrence and improving renal function in AHUS patients after renal transplantation treated with eculizumab: a systemic review and meta-analyses. Ren Fail. 2023;45(1). | |
| dc.relation.references | 20. Hsiung CY, Chen HY, Wang SH, Huang CY. Unveiling the Incidence and Graft Survival Rate in Kidney Transplant Recipients With De Novo Thrombotic Microangiopathy: A Systematic Review and Meta-Analysis. Transplant International. 2024 Jan 23;37. | |
| dc.relation.references | 21. Zhang R, Zhou M, Qi J, Miao W, Zhang Z, Wu D, et al. Efficacy and Safety of Eculizumab in the Treatment of Transplant-Associated Thrombotic Microangiopathy: A Systematic Review and Meta-Analysis. Front Immunol. 2021 Jan 20;11. | |
| dc.relation.references | 22. Dhanoa RK, Selvaraj R, Shoukrie SI, Zahra A, Malla J, Selvamani TY, et al. Eculizumab’s Unintentional Mayhem: A Systematic Review. Cureus. 2022 Jun 4; | |
| dc.relation.references | 23. Hilburg R, Geara AS, Qiu MK, Palmer MB, Chiang EY, Burger RA, et al. Bevacizumab-associated thrombotic microangiopathy treated with eculizumab: A case series and systematic review of the literature. Clin Nephrol. 2021 Jul 1;96(1):51–9. | |
| dc.relation.references | 24. Shahid K, Qayyum S. Eculizumab Versus Ravulizumab for the Treatment of Atypical Hemolytic Uremic Syndrome: A Systematic Review. Cureus. 2023 Sep 29; | |
| dc.relation.references | 25. Yang J, Xu X, Han S, Qi J, Li X, Pan T, et al. Comparison of multiple treatments in the management of transplant-related thrombotic microangiopathy: a network meta-analysis. Ann Hematol. 2023 Jan 1;102(1):31–9. | |
| dc.relation.references | 26. Wright RD, Bannerman F, Beresford MW, Oni L. A systematic review of the role of eculizumab in systemic lupus erythematosus-associated thrombotic microangiopathy. BMC Nephrol. 2020 Jun 30;21(1). | |
| dc.relation.references | 27. de Souza RM, Correa BHM, Melo PHM, Pousa PA, de Mendonça TSC, Rodrigues LGC, et al. The treatment of atypical hemolytic uremic syndrome with eculizumab in pediatric patients: a systematic review. Pediatric Nephrology. 2023 Jan 1;38(1):61–75. | |
| dc.relation.references | 28. de Zwart PL, Mueller TF, Spartà G, Luyckx VA. Eculizumab in Shiga toxin-producing Escherichia coli hemolytic uremic syndrome: a systematic review. Pediatric Nephrology. 2024 May 1;39(5):1369–85. | |
| dc.relation.references | 29. Gupta M, Govindappagari S, Burwick RM. Pregnancy-Associated Atypical Hemolytic Uremic Syndrome: A Systematic Review. Obstetrics and Gynecology. 2020 Jan 1;135(1):46–58. | |
| dc.relation.references | 30. Kaname S, Ong ML, Mathias J, Gatta F, Law L, Wang Y. Outcomes in patients with thrombotic microangiopathy associated with a trigger following plasma exchange: A systematic literature review. Transfusion and Apheresis Science. 2025 Feb 1;64(1). | |
| dc.relation.references | 31. Trisolini SM, Laganà A, Capria S. Immune Thrombotic Thrombocytopenic Purpura: Pathophysiology, Diagnosis, Therapy and Open Issues. Mediterr J Hematol Infect Dis. 2024;16(1). | |
| dc.relation.references | 32. Liu W, Zhu X, Xiao Y. Neurological involvement in hematopoietic stem cell transplantation-associated thrombotic microangiopathy. Ann Hematol. 2024 Sep 1;103(9):3303–13. | |
| dc.relation.references | 33. Vorobev A, Bitsadze V, Yagubova F, Khizroeva J, Solopova A, Tretyakova M, et al. The Phenomenon of Thrombotic Microangiopathy in Cancer Patients. Int J Mol Sci. 2024 Aug 1;25(16). | |
| dc.relation.references | 34. Mubarak M, Raza A, Rashid R, Sapna F, Shakeel S. Thrombotic microangiopathy after kidney transplantation: Expanding etiologic and pathogenetic spectra. World J Transplant. 2024 Mar 18;14(1). | |
| dc.relation.references | 35. Frimat M, Gnemmi V, Stichelbout M, Provôt F, Fakhouri F. Pregnancy as a susceptible state for thrombotic microangiopathies. Front Med (Lausanne). 2024;11. | |
| dc.relation.references | 36. Urra M, Lyons S, Teodosiu CG, Burwick R, Java A. Thrombotic Microangiopathy in Pregnancy: Current Understanding and Management Strategies. Kidney Int Rep. 2024 Aug 1;9(8):2353–71. | |
| dc.rights.accessrights | info:eu-repo/semantics/closedAccess | |
| dc.rights.accessrights | http://purl.org/coar/access_right/c_14cb | |
| dc.rights.local | Acceso cerrado | spa |
| dc.subject | Microangiopathic thrombocytopenic purpura | |
| dc.subject | Thrombotic microangiopathies | |
| dc.subject | Hemolytic-Uremic Syndrome | |
| dc.subject | Purpura, Thrombotic Thrombocytopenic | |
| dc.subject | Eculizumab | |
| dc.subject.keywords | Purpura trombocitopenica microangiopatica | |
| dc.subject.keywords | Microangiopatia trombotica | |
| dc.subject.keywords | Sindrome hemolitico uremico atipico | |
| dc.subject.keywords | Purpura trombocitopenica trombotica | |
| dc.subject.keywords | Eculizumab | |
| dc.subject.nlm | WA 105 | |
| dc.title | Uso de eculizumab en el tratamiento de microangiopatía trombótica: Revisión sistemática y metaanálisis | |
| dc.title.translated | Use of eculizumab in the treatment of thrombotic microangiopathies: Systematic review and metaanalysis | |
| dc.type.coar | https://purl.org/coar/resource_type/c_bdcc | |
| dc.type.coarversion | https://purl.org/coar/version/c_ab4af688f83e57aa | |
| dc.type.driver | info:eu-repo/semantics/masterThesis | |
| dc.type.hasversion | info:eu-repo/semantics/acceptedVersion | |
| dc.type.local | Tesis/Trabajo de grado - Monografía - Maestría | spa |
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