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. 2021 Aug;34(4):1373-1380.
doi: 10.1007/s40620-020-00920-z. Epub 2021 Jan 2.

Eculizumab interruption in atypical hemolytic uremic syndrome due to shortage: analysis of a Brazilian cohort

Miguel Ernandes Neto  1   2 , Lucas de Moraes Soler  3 , Halita Vieira Gallindo Vasconcelos  4 , Hong Si Nga  3 , Ariane Moyses Bravin  3 , Julio Cesar Andriotti Borges  5 , Rodrigo Costa Gonçalves  6 , Rodrigo Brum Von Kriiger  6 , Raquel Martins Quinino  7 , Viviane Brandão Bandeira de Mello Santana  8 , Maria Izabel de Holanda  9 , Maria Helena Vaisbich  10 , Alice Pignaton Naseri  11 , Gianna Mastroianni Kirsztajn  12 , Lilian Monteiro Pereira Palma  13 , Luís Gustavo Modelli Andrade  3
Affiliations

Eculizumab interruption in atypical hemolytic uremic syndrome due to shortage: analysis of a Brazilian cohort

Miguel Ernandes Neto et al. J Nephrol. 2021 Aug.

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.

Keywords: Atypical hemolytic uremic syndrome; Complement inactivating agents; Eculizumab.

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References

    1. Goodship THJ, Cook HT, Fakhouri F, Fervenza FC, Frémeaux-Bacchi V, Kavanagh D et al (2017) Atypical hemolytic uremic syndrome and C3 glomerulopathy: conclusions from a “Kidney Disease: Improving Global Outcomes” (KDIGO) Controversies Conference. Kidney Int 91(3):539–551 - DOI
    1. Legendre CM, Licht C, Muus P, Greenbaum LA, Babu S, Bedrosian C et al (2013) Terminal complement inhibitor eculizumab in atypical hemolytic-uremic syndrome. N Engl J Med. 368(23):2169–2181 - DOI
    1. Licht C, Greenbaum LA, Muus P, Babu S, Bedrosian CL, Cohen DJ et al (2015) Efficacy and safety of eculizumab in atypical hemolytic uremic syndrome from 2-year extensions of phase 2 studies. Kidney Int 87(5):1061–1073 - DOI
    1. Fakhouri F, Hourmant M, Campistol JM, Cataland SR, Espinosa M, Gaber AO et al (2016) Terminal complement inhibitor eculizumab in adult patients with atypical hemolytic uremic syndrome: a single-arm, open-label trial. Am J Kidney Dis 68(1):84–93 - DOI
    1. Greenbaum LA, Fila M, Ardissino G, Al-Akash SI, Evans J, Henning P et al (2016) Eculizumab is a safe and effective treatment in pediatric patients with atypical hemolytic uremic syndrome. Kidney Int 89(3):701–711 - DOI

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