Atypical hemolytic uremic syndrome

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Benjamin Tillman, MD
Vanderbilt University
Nashville, TN, USA

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2 regimens on this page
2 variants on this page


All lines of therapy

Eculizumab monotherapy

Regimen

FDA-recommended dose
Study Dates of enrollment Evidence
Legendre et al. 2013 (C08-002) Not reported Phase 2 (RT)
Legendre et al. 2013 (C08-003) Not reported Phase 2 (RT)
Cofiell et al. 2015 (C10-004) Not reported Non-randomized (RT)
Greenbaum et al. 2016 (C10-003) Not reported Phase 2

Note: Eligible patients enrolled in C10-004 had platelet counts less than 150 x 109/L, hemoglobin levels less than or equal to the lower limit of normal, LDH levels greater than or equal to 1.5x upper limit of normal, serum creatinine levels greater than or equal to the upper limit of normal, ADAMTS13 activity greater than or equal to 5%, and no positive Shiga toxin-producing Escherichia coli test.

Immunosuppressive therapy

  • Eculizumab (Soliris) as follows:
    • Cycles 1 to 4: 900 mg IV once on day 1
    • Cycle 5 onwards: 1200 mg IV once on day 1

Supportive therapy

  • Patients were vaccinated against Neisseria meningitidis or received "appropriate antibiotics" if vaccination occurred within 14 days of the first dose

7-day cycle for 4 cycles, then 14-day cycles

References

  1. C08-002: Legendre CM, Licht C, Muus P, Greenbaum LA, Babu S, Bedrosian C, Bingham C, Cohen DJ, Delmas Y, Douglas K, Eitner F, Feldkamp T, Fouque D, Furman RR, Gaber O, Herthelius M, Hourmant M, Karpman D, Lebranchu Y, Mariat C, Menne J, Moulin B, Nürnberger J, Ogawa M, Remuzzi G, Richard T, Sberro-Soussan R, Severino B, Sheerin NS, Trivelli A, Zimmerhackl LB, Goodship T, Loirat C. Terminal complement inhibitor eculizumab in atypical hemolytic uremic syndrome. N Engl J Med. 2013 Jun 6;368(23):2169-81. link to original article PubMed NCT00844545; NCT00844844
  2. C08-003: Legendre CM, Licht C, Muus P, Greenbaum LA, Babu S, Bedrosian C, Bingham C, Cohen DJ, Delmas Y, Douglas K, Eitner F, Feldkamp T, Fouque D, Furman RR, Gaber O, Herthelius M, Hourmant M, Karpman D, Lebranchu Y, Mariat C, Menne J, Moulin B, Nürnberger J, Ogawa M, Remuzzi G, Richard T, Sberro-Soussan R, Severino B, Sheerin NS, Trivelli A, Zimmerhackl LB, Goodship T, Loirat C. Terminal complement inhibitor eculizumab in atypical hemolytic uremic syndrome. N Engl J Med. 2013 Jun 6;368(23):2169-81. link to original article PubMed NCT00838513; NCT00844428
  3. C10-004: Cofiell R, Kukreja A, Bedard K, Yan Y, Mickle AP, Ogawa M, Bedrosian CL, Faas SJ. Eculizumab reduces complement activation, inflammation, endothelial damage, thrombosis, and renal injury markers in aHUS. Blood. 2015 May 21;125(21):3253-62. Epub 2015 Apr 1. link to original article link to PMC article contains dosing details in manuscript PubMed NCT01194973
  4. C10-003: Greenbaum LA, Fila M, Ardissino G, Al-Akash SI, Evans J, Henning P, Lieberman KV, Maringhini S, Pape L, Rees L, van de Kar NC, Vande Walle J, Ogawa M, Bedrosian CL, Licht C. Eculizumab is a safe and effective treatment in pediatric patients with atypical hemolytic uremic syndrome. Kidney Int. 2016 Mar;89(3):701-11. Epub 2016 Jan 28. link to original article PubMed NCT01193348

Ravulizumab monotherapy

Regimen

Study Dates of enrollment Evidence
Rondeau et al. 2020 (ALXN1210-aHUS-311) Not reported Nonrandomized Phase 3
Tanaka et al. 2020 (ALXN1210-aHUS-312) Not reported Nonrandomized Phase 3

Immunosuppressive therapy

References

  1. ALXN1210-aHUS-311: Rondeau E, Scully M, Ariceta G, Barbour T, Cataland S, Heyne N, Miyakawa Y, Ortiz S, Swenson E, Vallee M, Yoon SS, Kavanagh D, Haller H; 311 Study Group. The long-acting C5 inhibitor, Ravulizumab, is effective and safe in adult patients with atypical hemolytic uremic syndrome naïve to complement inhibitor treatment. Kidney Int. 2020 Jun;97(6):1287-1296. Epub 2020 Mar 6. Erratum in: Kidney Int. 2020 Dec;98(6):1621. Erratum in: Kidney Int. 2021 May;99(5):1244. link to original article PubMed NCT02949128
  2. ALXN1210-aHUS-312: Tanaka K, Adams B, Aris AM, Fujita N, Ogawa M, Ortiz S, Vallee M, Greenbaum LA. The long-acting C5 inhibitor, ravulizumab, is efficacious and safe in pediatric patients with atypical hemolytic uremic syndrome previously treated with eculizumab. Pediatr Nephrol. 2021 Apr;36(4):889-898. Epub 2020 Oct 13. Erratum in: Pediatr Nephrol. 2020 Dec 9. link to original article link to PMC article PubMed NCT03131219