What is atypical‑HUS?
Atypical hemolytic uremic syndrome (atypical‑HUS) is a rare, life-threatening disease caused by dysregulation of the alternative pathway of the complement system, leading to excessive complement activation and thrombotic microangiopathy (TMA).1-3
For treatment of atypical-HUS in adults and pediatric patients 1 month of age and older. Not indicated in STEC‑HUS.4
Complement system dysfunction in atypical‑HUS5-8
In atypical‑HUS, the complement part of the innate immune system is over-activated. This chronic activation leads to microvascular damage, thrombosis, and multi-organ ischemic damage.5
TMA triggersThrombotic microangiopathy (TMA) can be associated with various triggers3
Atypical‑HUS may be triggered by conditions that activate complement.3 Persistence of TMA despite treatment of associated conditions may suggest atypical‑HUS.9
Triggers that may accelerate activation of the complement system3
Surgery or trauma
Surgery or trauma
Differential diagnosis Diagnosing atypical‑HUS requires excluding other conditions3,9
Many of the signs and symptoms of atypical‑HUS are shared by other causes of TMA.3 Because of its high morbidity and mortality when untreated, identifying atypical‑HUS quickly is important.3,9
bShiga toxin/EHEC test is warranted with history/presence of gastrointestinal symptoms.
cRange found in published data is 5%-10%.
ADAMTS13=a disintegrin and metalloproteinase with a thrombospondin type 1 motif member 13; CV=cardiovascular; EHEC=enterohemorrhagic Escherichia coli; eGFR=estimated glomerular filtration rate; GI=gastrointestinal; HUS=hemolytic uremic syndrome; LDH=lactate dehydrogenase; MI=myocardial infarction; sCr=serum creatinine; STEC=Shiga toxin-producing Escherichia coli; TTP=thrombotic thrombocytopenic purpura.
ULTOMIRIS is the first and only long-acting complement inhibitor for atypical‑HUS1
Your atypical‑HUS patients on ULTOMIRIS can get up to 8 weeksd of continuous protection between infusions.1
dStarting 2 weeks after the loading dose, maintenance doses are administered once every 4 or 8 weeks (depending on body weight).1SEE HOW IT WORKS
- Asif A, et al. J Nephrol. 2017;30:347-362.
- Jamme M, et al. PLoS One. 2017;12:e0177894.
- Laurence J. Clin Adv Hematol Oncol. 2016;14:2-15.
- ULTOMIRIS [prescribing information]. Boston, MA: Alexion Pharmaceuticals, Inc.; 2020.
- Raina R, et al. Ther Apher Dial. 2019;23:4-21.
- Legendre CM, et al. N Engl J Med. 2013;368:2169-2181.
- Goodship THJ, et al. Kidney Int. 2017;91:539-551.
- Nester CM, et al. Hematology Am Soc Hematol Educ Program. 2012;2012:617-625.
- Azoulay E, et al. Chest. 2017;152:424-434.
IMPORTANT SAFETY INFORMATION INCLUDING BOXED WARNING
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 Advisory Committee on Immunization Practices (ACIP) recommendations for meningococcal vaccination in patients with complement deficiencies.
- Immunize patients with meningococcal vaccines at least 2 weeks prior to administering the first dose of ULTOMIRIS, unless the risks of delaying ULTOMIRIS therapy outweigh the risk of developing a meningococcal infection. See Warnings and Precautions for additional guidance on the management of the risk of meningococcal infection.
- Vaccination reduces, but does not eliminate, the risk of meningococcal infections. Monitor patients for early signs of meningococcal infections and evaluate immediately if infection is suspected.
ULTOMIRIS is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS). Under the ULTOMIRIS REMS, prescribers must enroll in the program. Enrollment in the ULTOMIRIS REMS program and additional information are available by telephone: 1-888-765-4747 or at www.ultomirisrems.com.
- Patients with unresolved Neisseria meningitidis infection.
- Patients who are not currently vaccinated against Neisseria meningitidis, unless the risks of delaying ULTOMIRIS treatment outweigh the risks of developing a meningococcal infection.
WARNINGS AND PRECAUTIONS
Serious Meningococcal Infections
Risk and Prevention
Life-threatening meningococcal infections have occurred in patients treated with ULTOMIRIS. The use of ULTOMIRIS increases a patient’s susceptibility to serious meningococcal infections (septicemia and/or meningitis). Meningococcal disease due to any serogroup may occur.
Vaccinate or revaccinate for meningococcal disease according to the most current ACIP recommendations for patients with complement deficiencies. Immunize patients without history of meningococcal vaccination at least 2 weeks prior to the first dose of ULTOMIRIS. If ULTOMIRIS must be initiated immediately in an unvaccinated patient, administer meningococcal vaccine(s) as soon as possible and provide 2 weeks of antibacterial drug prophylaxis. The benefits and risks of antibiotic prophylaxis for prevention of meningococcal infections in patients receiving ULTOMIRIS have not been established. Consider discontinuation of ULTOMIRIS in patients who are undergoing treatment for serious meningococcal infection.
Under the ULTOMIRIS REMS, prescribers must enroll in the program due to the risk of meningococcal infections. Prescribers must counsel patients about the risk of meningococcal infection/sepsis, provide the patients with the REMS educational materials, and ensure patients are vaccinated with meningococcal vaccines.
Patients may have increased susceptibility to encapsulated bacteria infections, especially infections caused by Neisseria meningitidis but also Streptococcus pneumoniae, Haemophilus influenzae, and to a lesser extent, Neisseria gonorrhoeae. Children treated with ULTOMIRIS may be at increased risk of developing serious infections due to Streptococcus pneumoniae and Haemophilus influenzae type b (Hib). Administer vaccinations for the prevention of Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) infections according to ACIP guidelines. If ULTOMIRIS is administered to patients with active systemic infections, monitor closely for worsening infection.
Monitoring Disease Manifestations after ULTOMIRIS Discontinuation
ULTOMIRIS treatment of aHUS should be a minimum duration of 6 months. Due to heterogeneous nature of aHUS events and patient-specific risk factors, treatment duration beyond the initial 6 months should be individualized. There are no specific data on ULTOMIRIS discontinuation. After discontinuing treatment with ULTOMIRIS, patients should be monitored for clinical symptoms and laboratory signs of TMA complications for at least 12 months.
TMA complications post-discontinuation can be identified if any of the following is observed: Clinical symptoms of TMA include changes in mental status, seizures, angina, dyspnea, thrombosis or increasing blood pressure. In addition, at least two of the following laboratory signs observed concurrently and results should be confirmed by a second measurement 28 days apart with no interruption: a decrease in platelet count of 25% or more as compared to either baseline or to peak platelet count during ULTOMIRIS treatment; an increase in serum creatinine of 25% or more as compared to baseline or to nadir during ULTOMIRIS treatment; or, an increase in serum LDH of 25% or more as compared to baseline or to nadir during ULTOMIRIS treatment. If TMA complications occur after discontinuation, consider reinitiation of ULTOMIRIS treatment or appropriate organ-specific supportive measures.
Thromboembolic Event Management
The effect of withdrawal of anticoagulant therapy during treatment with ULTOMIRIS has not been established. Treatment should not alter anticoagulant management.
Administration of ULTOMIRIS may result in infusion-related reactions. In clinical trials, 5 out of 296 patients treated with ULTOMIRIS experienced infusion-related reactions (lower back pain, drop in blood pressure, infusion-related pain, elevation in blood pressure and limbs discomfort) during ULTOMIRIS administration which did not require discontinuation. Interrupt infusion and institute supportive measures if signs of cardiovascular instability or respiratory compromise occur.
Most common adverse reactions in patients with aHUS (incidence ≥20%) were upper respiratory tract infection, diarrhea, nausea, vomiting, headache, hypertension and pyrexia. Serious adverse reactions were reported in 42 (57%) patients with aHUS receiving ULTOMIRIS. The most frequent serious adverse reactions reported in more than 2 patients (2.7%) treated with ULTOMIRIS were hypertension, pneumonia and abdominal pain. In clinical studies, clinically relevant adverse reactions in <10% of patients include viral tonsillitis in adults and viral infection in pediatric patients.
ULTOMIRIS is indicated for the treatment of adults and pediatric patients one month of age and older with atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy (TMA).
Limitation of Use:
ULTOMIRIS is not indicated for the treatment of patients with Shiga toxin E. coli related hemolytic uremic syndrome (STEC‑HUS).