aHUS is a chronic and life-threatening disease driven by complement-mediated TMA1–5
In aHUS, the alternate complement pathway can be inappropriately active and target endothelial cells rather than infectious invaders.6

The endothelial cells are then damaged or destroyed leading to a TMA, with clotting in the small vessels and ischemic damage to the downstream organs.6

Often there is a precipitating infection, illness, or event (e.g., surgery or pregnancy) that activates the alternate complement pathway, but then this system fails to turn itself off.6,7

Every organ in the body can be damaged.8
The brain and kidneys are most often affected, with loss of kidney function a common result. Mortality in the first episode is 10–15%, rising when diagnosis and treatment is delayed.

A.K.A. Complement-mediated Hemolytic Uremic Syndrome (CM-HUS)

Inappropriate activation of the alternate complement pathway
  • Gain of function mutations in promoters
  • Loss of function mutations in inhibitors
  • Inhibitor antibody
  • Up to 30% don’t have a known mutation or antibody9
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ULTOMIRIS® and SOLIRIS® are C5 inhibitors indicated for aHUS

ULTOMIRIS® (ravulizumab for injection) is indicated for the treatment of adult and pediatric patients one month of age and older with atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic hemolysis (TMA).

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SOLIRIS® (eculizumab for injection) is indicated for the treatment of patients with atypical hemolytic uremic syndrome (aHUS) to reduce complement-mediated thrombotic microangiopathy.

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30%

of all patients progress to end-stage renal disease (ESRD) or die with the first clinical manifestation11
79%

of all patients have permanent renal damage, require dialysis, or die within 3 years9
Modified from Caprioli et al. 2006.11
Study description: An analysis of the outcomes in 40 patients with the complement factor H (CFH) mutation.
The cumulative fraction of patients free of events was estimated by Kaplan–Meier analysis.11
Modified from Noris et al. 2010.9
Study description: Analysis of 191 patients with aHUS and data available for reports of triggering/underlying conditions, registered consecutively from 1996 to 2007 within the International Registry of Recurrent and Familial HUS/TTP.9
*E.g., systemic lupus erythematosus and scleroderma.

Persistent TMA, however, is uncommon in these complementamplifying conditions once adequately treated.12
Remission can be broadly defined as maintaining each of the following for 3–6 months:13–15
Normalization of platelet count, LDH, and haptoglobin
Stabilization of kidney function (including stabilization of residual CKD)
Optimal control of blood pressure and other* extrarenal manifestations
*Extrarenal manifestations may include: digital gangrene, skin; cerebral artery thrombosis/stenosis; extracerebral artery stenosis; cardiac involvement/myocardial infarction; ocular involvement; neurologic involvement; pancreatic, gastrointestinal involvement; pulmonary involvement; intestinal involvement13
See the rapid and sustained efficacy of ULTOMIRIS® in delivering remission for patients with aHUS
Learn more about the importance of continuous C5 inhibition and TMA relapse in patients with aHUS
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CKD, chronic kidney disease; TMA, thrombotic microangiopathy; TTP, thrombotic thrombocytopenic purpura
ULTOMIRIS®
Indications and Clinical Use:
ULTOMIRIS® (ravulizumab for injection) is indicated for:
  • The treatment of adult and pediatric patients one month of age and older with atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic hemolysis (TMA)

Limitations of Use: ULTOMIRIS® is not indicated for the treatment of patients with Shiga toxin E. coli related hemolytic uremic syndrome (STEC-HUS).

Contraindications:
  • Do not initiate ULTOMIRIS® in patients with unresolved Neisseria meningitidis infection

Most Serious Warnings and Precautions:
WARNING: SERIOUS MENINGOCOCCAL INFECTIONS
Life-threatening meningococcal infections/sepsis have occurred in patients treated with ULTOMIRIS®. Meningococcal infection may become rapidly life-threatening or fatal if not recognized and treated early.
  • Comply with the most current National Advisory Committee on Immunization (NACI) recommendations for meningococcal vaccination in patients with complement deficiencies.
  • Patients must be vaccinated against meningococcal infections prior to, or at the time of, initiating ULTOMIRIS®, unless the risks of delaying ULTOMIRIS® therapy outweigh the risks of developing a meningococcal infection.
  • Monitor patients for early signs of meningococcal infections and treat immediately if infection is suspected.
ULTOMIRIS® in Canada is available under a controlled distribution program. Patients are enrolled in a dedicated Patient Support Program (PSP).
For More Information:
Please consult the product monograph https://alexion.com/documents/ultomiris_product_monograph_approved_english for important information relating to adverse reactions, drug interactions, and dosing information which have not been discussed in this piece. The product monograph is also available by calling 1-844-922-0605.
SOLIRIS®
Indications and Clinical Use:
SOLIRIS® (eculizumab for injection) is indicated for:
  • The treatment of patients with atypical hemolytic uremic syndrome (aHUS) to reduce complement-mediated thrombotic microangiopathy.
Limitations of Use: SOLIRIS® is not indicated for the treatment of patients with Shiga toxin E. coli related hemolytic uremic syndrome (STEC-HUS).

Contraindications:
Do not initiate SOLIRIS® in patients:
  • with unresolved Neisseria meningitidis infection
  • who are not currently vaccinated against Neisseria meningitidis (unless they receive prophylactic treatment with appropriate antibiotics until 2 weeks after vaccination)

Most Serious Warnings and Precautions:
SERIOUS WARNINGS AND PRECAUTIONS
Cases of serious or fatal meningococcal infections have been reported in patients treated with SOLIRIS®. Meningococcal infections may become rapidly life-threatening or fatal if not recognized and treated early.
  • Comply with the most current National Advisory Committee on Immunization (NACI) recommendations for meningococcal vaccination in patients with complement deficiencies.
  • All patients must be vaccinated with meningococcal vaccines prior to, or at the time of, initiating SOLIRIS®, unless the risks of delaying SOLIRIS® therapy outweigh the risks of developing a meningococcal infection; revaccinate according to current medical guidelines for vaccine use.
  • All patients must be monitored for early signs of meningococcal infections, evaluated immediately if infection is suspected, and treated with antibiotics, if necessary.
Vaccination may not prevent all meningococcal infections.
For More Information:
Please consult the product monograph https://alexion.com/-/media/alexion_global/documents/regulatory/north-america/canada/2024/english/soliris_product_monograph_en_approved_24jul2024.pdf for important information relating to adverse reactions, drug interactions, and dosing information which have not been discussed in this piece. The product monograph is also available by calling 1-844-922-0605.
Legendre CM, et al. Terminal complement inhibitor eculizumab in atypical hemolytic–uremic syndrome. N Engl J Med. 2013;368(23):2169-2181. Loirat C, Noris M, Fremeaux-Bacchi V. Complement and the atypical hemolytic uremic syndrome in children. Pediatr Nephrol. 2008;23(11):1957-1972. Hirt-Minkowski P, Dickenmann M, Schifferli J. Atypical hemolytic uremic syndrome: Update on the complement system and what is new. Nephron Clin Pract. 2010;114:c219-c235. Fang CJ, et al. Advances in understanding of pathogenesis of aHUS and HELLP. Br J Haematol. 2008;143(3):336-348. ULTOMIRIS® Product Monograph. Alexion Pharmaceuticals, Inc. October 30, 2023. McFarlane PA, et al. Making the correct diagnosis in thrombotic microangiopathy: A narrative review. Can J Kidney Health Dis. 2021;8:1-12. Raina R, et al. Atypical hemolytic-uremic syndrome: An update on pathophysiology, diagnosis, and treatment. Ther Apher Dial. 2019;23(1):4-21. Campistol JM, et al. An update for atypical haemolytic uraemic syndrome: Diagnosis and treatment. A consensus document. Nefrologia. 2015;35(5):421-47. Noris M, 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(10):1844-1859. Kelly R, Richards S, Hillmen P, Hill A. The pathophysiology of paroxysmal nocturnal hemoglobinuria and treatment with eculizumab. Ther Clin Risk Manag. 2009;5:911-921. Caprioli J, et al. Genetics of HUS: The impact of MCP, CFH, and IF mutations on clinical presentation, response to treatment, and outcome. Blood. 2006;108(4):1267-1279. Asif A, Nayer A, Hass CS. Atypical hemolytic uremic syndrome in the setting of complement-amplifying conditions: Case reports and a review of the evidence for treatment with eculizumab. J Nephrol. 2017;30(3):347-362. Goodship THJ, et al. Atypical hemolytic uremic syndrome and C3 glomerulopathy: Conclusions from a “Kidney Disease: Improving Global Outcomes” (KDIGO) Controversies Conference. Kidney Int. 2017;91(3):539-551. Laurence J. Defining treatment duration in atypical hemolytic uremic syndrome in adults: A clinical and pathological approach. Clin Adv Hematol Oncol. 2020;18(4):221-230. Loirat C, et al. An international consensus approach to the management of atypical hemolytic uremic syndrome in children. Pediatr Nephrol. 2016;31(1):15-39.