The global aHUS registry: methodology and initial patient characteristics

Christoph Licht, Gianluigi Ardissino, Gema Ariceta, David Cohen, J Alexander Cole, Christoph Gasteyger, Larry A Greenbaum, Sally Johnson, Masayo Ogawa, Franz Schaefer, Johan Vande Walle, Véronique Frémeaux-Bacchi, Christoph Licht, Gianluigi Ardissino, Gema Ariceta, David Cohen, J Alexander Cole, Christoph Gasteyger, Larry A Greenbaum, Sally Johnson, Masayo Ogawa, Franz Schaefer, Johan Vande Walle, Véronique Frémeaux-Bacchi

Abstract

Background: Atypical hemolytic uremic syndrome (aHUS) is a rare, genetically-mediated systemic disease most often caused by chronic, uncontrolled complement activation that leads to systemic thrombotic microangiopathy (TMA) and renal and other end-organ damage.

Methods: The global aHUS Registry, initiated in April 2012, is an observational, noninterventional, multicenter registry designed to collect demographic characteristics, medical and disease history, treatment effectiveness and safety outcomes data for aHUS patients. The global aHUS Registry will operate for a minimum of 5 years of follow-up. Enrollment is open to all patients with a clinical diagnosis of aHUS, with no requirement for identified complement gene mutations, polymorphisms or autoantibodies or particular type of therapy/management.

Results: As of September 30, 2014, 516 patients from 16 countries were enrolled. At enrollment, 315 (61.0 %) were adults (≥18 years) and 201 (39.0 %) were <18 years of age. Mean (standard deviation [SD]) age at diagnosis was 22.7 (20.5) years. Nineteen percent of patients had a family history of aHUS, 60.3 % had received plasma exchange/plasma infusion, 59.5 % had a history of dialysis, and 19.6 % had received ≥1 kidney transplant. Overall, 305 patients (59.1 %) have received eculizumab.

Conclusions: As enrollment and follow-up proceed, the global aHUS Registry is expected to yield valuable baseline, natural history, medical outcomes, treatment effectiveness and safety data from a diverse population of patients with aHUS.

Trial registration: US National Institutes of Health www.ClinicalTrials.gov Identifier NCT01522183 . Registered January 18, 2012.

References

    1. Noris M, Remuzzi G. Atypical hemolytic-uremic syndrome. N Engl J Med. 2009;361:1676–87. doi: 10.1056/NEJMra0902814.
    1. Fremeaux-Bacchi V, Fakhouri F, Garnier A, Bienaime F, Dragon-Durey MA, Ngo S, 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.
    1. Zipfel PF, Heinen S, Skerka C. Thrombotic microangiopathies: new insights and new challenges. Curr Opin Nephrol Hypertens. 2010;19:372–8. doi: 10.1097/MNH.0b013e32833aff4a.
    1. Noris M, Caprioli J, Bresin E, Mossali C, Pianetti G, Gamba S, et al. Relative role of genetic complement abnormalities in sporadic and familial aHUS and their impact on clinical phenotype. Clin J Am Soc Nephrol. 2010;5:1844–59. doi: 10.2215/CJN.02210310.
    1. Rodriguez de Cordoba S, Hidalgo MS, Pinto S, Tortajada A. Genetics of Atypical Hemolytic Uremic Syndrome (aHUS) Semin Thromb Hemost. 2014;40:422–30. doi: 10.1055/s-0034-1375296.
    1. Zuber J, Fakhouri F, Roumenina LT, Loirat C, Fremeaux-Bacchi V. Use of eculizumab for atypical haemolytic uraemic syndrome and C3 glomerulopathies. Nat Rev Nephrol. 2012;8:643–57. doi: 10.1038/nrneph.2012.214.
    1. Campistol JM, Arias M, Ariceta G, Blasco M, Espinosa M, Grinyo JM, et al. An update for atypical haemolytic uraemic syndrome: diagnosis and treatment. A consensus document. Nefrologia. 2013;33:27–45.
    1. Delvaeye M, Noris M, De Vriese A, Esmon CT, Esmon NL, Ferrell G, et al. Thrombomodulin mutations in atypical hemolytic-uremic syndrome. N Engl J Med. 2009;361:345–57. doi: 10.1056/NEJMoa0810739.
    1. Lemaire M, Fremeaux-Bacchi V, Schaefer F, Choi M, Tang WH, Le Quintrec M, et al. Recessive mutations in DGKE cause atypical hemolytic-uremic syndrome. Nat Genet. 2013;45:531–6. doi: 10.1038/ng.2590.
    1. Bu F, Maga T, Meyer NC, Wang K, Thomas CP, Nester CM, et al. Comprehensive genetic analysis of complement and coagulation genes in atypical hemolytic uremic syndrome. J Am Soc Nephrol. 2014;25:55–64. doi: 10.1681/ASN.2013050453.
    1. US Food and Drug Administration. Soliris (eculizumab) [prescribing information]. Cheshire, CT: Alexion Pharmaceuticals, Inc.; 2014.
    1. European Medicines Agency . Soliris (eculizumab) [summary of product characteristics] Paris: Alexion Europe SAS; 2015.
    1. 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. 2013;368:2169–81. doi: 10.1056/NEJMoa1208981.
    1. Licht C, Greenbaum LA, Muus P, Babu S, Bedrosian CL, Cohen DJ, 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. doi: 10.1038/ki.2014.423.
    1. Vilalta R, Al-Akash S, Davin J, Diaz J, Gruppo R, Hernandez J, et al. Eculizumab therapy for pediatric patients with atypical hemolytic uremic syndrome: efficacy and safety outcomes of a retrospective study [abstract 1155] Haematologica. 2012;97(suppl 1):479.
    1. Fakhouri F, Hourmant M, Campistol JM, Cataland SR, Espinosa M, Gaber AO, et al. Eculizumab (ECU) inhibits thrombotic microangiopathy (TMA) and improves renal function in adult atypical hemolytic uremic syndrome (aHUS) patients (Pts) [abstract FR-OR057] J Am Soc Nephrol. 2013;24:49A–50A.
    1. Greenbaum LA, Fila M, Tsimaratos M, Ardissino G, Al-Akash SI, Evans J, et al. Eculizumab (ECU) inhibits thrombotic microangiopathy (TMA) and improves renal function in pediatric atypical hemolytic uremic syndrome (aHUS) patients (Pts) [abstract SA-PO849] J Am Soc Nephrol. 2013;24:821A–2A.
    1. Gliklich RE, Dreyer NA. Registries for Evaluating Patient Outcomes: A User's Guide. (Prepared by Outcome DEcIDE Center [Outcome Sciences, Inc. dba Outcome] under Contract No. HHSA29020050035IT01.) AHRQ Publication No. 07-EHC001-1. Agency for Healthcare Research and Quality; 2007. [].
    1. Ayme S, Rodwell C. 2013 Report on the State of the Art of Rare Disease Activities in Europe. Part I: Overview of Rare Disease Activities in Europe. Paris: European Union Committee of Experts on Rare Diseases; 2013.
    1. Coppo P, Schwarzinger M, Buffet M, Wynckel A, Clabault K, Presne C, et al. Predictive features of severe acquired ADAMTS13 deficiency in idiopathic thrombotic microangiopathies: the French TMA reference center experience. PLoS One. 2010;5:e10208. doi: 10.1371/journal.pone.0010208.
    1. Kremer Hovinga JA, Vesely SK, Terrell DR, Lammle B, George JN. Survival and relapse in patients with thrombotic thrombocytopenic purpura. Blood. 2010;115:1500–11. doi: 10.1182/blood-2009-09-243790.
    1. Loirat C, Garnier A, Sellier-Leclerc AL, Kwon T. Plasmatherapy in atypical hemolytic uremic syndrome. Semin Thromb Hemost. 2010;36:673–81. doi: 10.1055/s-0030-1262890.
    1. Michael M, Elliott EJ, Craig JC, Ridley G, Hodson EM. Interventions for hemolytic uremic syndrome and thrombotic thrombocytopenic purpura: a systematic review of randomized controlled trials. Am J Kidney Dis. 2009;53:259–72. doi: 10.1053/j.ajkd.2008.07.038.
    1. Fakhouri F, Fremeaux-Bacchi V, Loirat C. Atypical hemolytic uremic syndrome: from the rediscovery of complement to targeted therapy. Eur J Intern Med. 2013;24:492–5. doi: 10.1016/j.ejim.2013.05.008.
    1. Scully M, Goodship T. How I treat thrombotic thrombocytopenic purpura and atypical haemolytic uraemic syndrome. Br J Haematol. 2014;164:759–66. doi: 10.1111/bjh.12718.
    1. Benz K, Amann K. Thrombotic microangiopathy: new insights. Curr Opin Nephrol Hypertens. 2010;19:242–7. doi: 10.1097/MNH.0b013e3283378f25.
    1. Noris M, Remuzzi G. Cardiovascular complications in atypical haemolytic uraemic syndrome. Nat Rev Nephrol. 2014;10:174–80. doi: 10.1038/nrneph.2013.280.
    1. Akimoto T, Muto S, Ito C, Takahashi H, Takeda S, Ando Y, et al. Clinical features of malignant hypertension with thrombotic microangiopathy. Clin Exp Hypertens. 2011;33:77–83. doi: 10.3109/10641963.2010.503303.
    1. Barbour T, Johnson S, Cohney S, Hughes P. Thrombotic microangiopathy and associated renal disorders. Nephrol Dial Transplant. 2012;27:2673–85. doi: 10.1093/ndt/gfs279.
    1. Kavanagh D, Goodship THJ, Richards A. Atypical haemolytic uraemic syndrome. Br Med Bull. 2006;77 and 78:5–22. doi: 10.1093/bmb/ldl004.
    1. Nester CM, Thomas CP. Atypical hemolytic uremic syndrome: what is it, how is it diagnosed, and how is it treated? Hematology Am Soc Hematol Educ Program. 2012;2012:617–25.

Source: PubMed

Sponsor e collaboratori

Condizioni mediche

Interventi farmacologici

3
Sottoscrivi