Miguel Ernandes Neto1,2, Lucas de Moraes Soler3, Halita Vieira Gallindo Vasconcelos4, Hong Si Nga3, Ariane Moyses Bravin3, Julio Cesar Andriotti Borges5, Rodrigo Costa Gonçalves6, Rodrigo Brum Von Kriiger6, Raquel Martins Quinino7, Viviane Brandão Bandeira de Mello Santana8, Maria Izabel de Holanda9, Maria Helena Vaisbich10, Alice Pignaton Naseri11, Gianna Mastroianni Kirsztajn12, Lilian Monteiro Pereira Palma13, Luís Gustavo Modelli Andrade3. 1. Department of Internal Medicine, São Paulo State University (UNESP), Botucatu, SP, Brazil. m_ernandes@yahoo.com.br. 2. Hospital BP-a Beneficência Portuguesa de São Paulo, São Paulo, SP, Brazil. m_ernandes@yahoo.com.br. 3. Department of Internal Medicine, São Paulo State University (UNESP), Botucatu, SP, Brazil. 4. Departamento de Nefrologia da Santa Casa de São Carlos, São Carlos, SP, Brazil. 5. Fresenius Medical Care-Unidade Perdizes, São Paulo, SP, Brazil. 6. Hospital de Urgências Governador Otávio Lage de Siqueira (HUGOL), Goiânia, GO, Brazil. 7. Hospital Universitário Onofre Lopes, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil. 8. Instituto Hospital de Base, Brasília, DF, Brazil. 9. Hospital Federal de Bonsucesso-Serviço de Nefrologia e Transplante, Rio de Janeiro, RJ, Brazil. 10. Instituto da Criança-University of São Paulo, São Paulo, SP, Brazil. 11. Setor de Nefrologia da Unidade de Gestão de Transplantes da Universidade Federal do Espírito Santo, Vitória, ES, Brazil. 12. Departamento de Medicina (Nefrologia) da Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil. 13. Nefrologia Pediátrica-Departamento de Pediatria da Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brazil.
Abstract
BACKGROUND: The risk of eculizumab therapy discontinuation in patients with atypical hemolytic uremic syndrome (aHUS) is unclear. The main objective of this study was to analyze the risk of aHUS relapse after eculizumab interruption due to drug shortage in Brazil. METHODS: We screened all the registered dialysis centers in Brazil (n = 800), willing to participate in the aHUS Brazilian shortage cohort, through electronic mail and formal invitation by the Brazilian Society of Nephrology. We included patients with aHUS whose eculizumab therapy underwent unplanned discontinuation for at least 30 days between January 1st, 2016 and December 31st, 2019 during the maintenance phase of treatment. Relapse was defined by the development of thrombocytopenia, hemolytic anemia, acute kidney injury or thrombotic microangiopathy (TMA) in a kidney biopsy. RESULTS: We analyzed 25 episodes of exposure to risk of relapse, from 24 patients. Median age was 33 (6-53) years, 18 (72%) were female, 9 (36%) had a functioning renal graft, 5 (20%) were undergoing dialysis. CFH variant was found in 8 (32%) episodes. There were 11 relapses. The risk of relapse was 34%, 44.5% and 58% at 114, 150 and 397 days, respectively. No baseline variable was related to relapse in Cox multivariate analysis, including CFH variant. CONCLUSIONS: In this study, the cumulative incidence of aHUS relapse at 397 days was 58% after eculizumab interruption. The presence of complement variant does not seem to be associated with a higher relapse rate. The eculizumab interruption was deemed not safe, considering that the rate of relapse was high.
BACKGROUND: The risk of eculizumab therapy discontinuation in patients with atypical hemolytic uremic syndrome (aHUS) is unclear. The main objective of this study was to analyze the risk of aHUS relapse after eculizumab interruption due to drug shortage in Brazil. METHODS: We screened all the registered dialysis centers in Brazil (n = 800), willing to participate in the aHUS Brazilian shortage cohort, through electronic mail and formal invitation by the Brazilian Society of Nephrology. We included patients with aHUS whose eculizumab therapy underwent unplanned discontinuation for at least 30 days between January 1st, 2016 and December 31st, 2019 during the maintenance phase of treatment. Relapse was defined by the development of thrombocytopenia, hemolytic anemia, acute kidney injury or thrombotic microangiopathy (TMA) in a kidney biopsy. RESULTS: We analyzed 25 episodes of exposure to risk of relapse, from 24 patients. Median age was 33 (6-53) years, 18 (72%) were female, 9 (36%) had a functioning renal graft, 5 (20%) were undergoing dialysis. CFH variant was found in 8 (32%) episodes. There were 11 relapses. The risk of relapse was 34%, 44.5% and 58% at 114, 150 and 397 days, respectively. No baseline variable was related to relapse in Cox multivariate analysis, including CFH variant. CONCLUSIONS: In this study, the cumulative incidence of aHUS relapse at 397 days was 58% after eculizumab interruption. The presence of complement variant does not seem to be associated with a higher relapse rate. The eculizumab interruption was deemed not safe, considering that the rate of relapse was high.
Authors: Manuel Macia; Fernando de Alvaro Moreno; Tina Dutt; Ingela Fehrman; Karine Hadaya; Christoph Gasteyger; Nils Heyne Journal: Clin Kidney J Date: 2016-12-22
Authors: Hong Si Nga; Lilian Monteiro Pereira Palma; Miguel Ernandes Neto; Luis Gustavo Modelli de Andrade Journal: J Nephrol Date: 2022-04-02 Impact factor: 3.902
Authors: Hong Si Nga; Lilian Monteiro Pereira Palma; Miguel Ernandes Neto; Ida Maria Maximina Fernandes-Charpiot; Valter Duro Garcia; Roger Kist; Silvana Maria Carvalho Miranda; Pedro Augusto Macedo de Souza; Gerson Marques Pereira; Luis Gustavo Modelli de Andrade Journal: PLoS One Date: 2021-11-08 Impact factor: 3.240
Authors: Maria Helena Vaisbich; Luís Gustavo Modelli de Andrade; Precil Diego Miranda de Menezes Neves; Lílian Monteiro Pereira Palma; Maria Cristina Ribeiro de Castro; Cassiano Augusto Braga Silva; Maria Izabel Neves de Holanda Barbosa; Maria Goretti Moreira Guimarães Penido; Oreste Ângelo Ferra Neto; Roberta Mendes Lima Sobral; Silvana Maria Carvalho Miranda; Stanley de Almeida Araújo; Igor Gouveia Pietrobom; Henrique Mochida Takase; Cláudia Ribeiro; Rafael Marques da Silva; César Augusto Almeida de Carvalho; David José Barros Machado; Ana Mateus Simões Teixeira E Silva; Andreia Ribeiro da Silva; Enzo Ricardo Russo; Flávio Henrique Soares Barros; Jarinne Camilo Landim Nasserala; Luciana Schmitt Cardon de Oliveira; Lucimary de Castro Sylvestre; Rafael Weissheimer; Sueli Oliveira Nascimento; Gilson Bianchini; Fellype de Carvalho Barreto; Valéria Soares Pigozzi Veloso; Patrícia Marques Fortes; Vinicius Sardão Colares; Jaelson Guilhem Gomes; André Falcão Pedrosa Leite; Pablo Girardelli Mendonça Mesquita; Osvaldo Merege Vieira-Neto Journal: Clin Kidney J Date: 2022-04-11