Atypical hemolytic uremic syndrome

Section editor transclusions

2 regimens on this page 2 variants on this page

Guidelines

"How I Treat"

• 2023: Fakhouri et al. How I diagnose and treat atypical hemolytic uremic syndrome

All lines of therapy

Eculizumab monotherapy

Regimen

FDA-recommended dose

Study	Evidence
Legendre et al. 2013 (C08-002)	Phase 2 (RT)
Legendre et al. 2013 (C08-003)	Phase 2 (RT)
Cofiell et al. 2015 (C10-004)	Non-randomized (RT)
Greenbaum et al. 2016 (C10-003)	Phase 2

Note: Eligible patients enrolled in C10-004 had platelet counts less than 150 × 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:
  • Cycle 1: 900 mg IV once per day on days 1, 8, 15, 22
  • Cycle 2 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

28-day cycle for 1 cycle, 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