Eculizumab (Soliris) is now approved for use in adults and children with atypical hemolytic uremic syndrome, a rare and chronic blood disease that affects children more than adults and can lead to renal failure, stroke, or death. Eculizumab was already approved for use in the treatment of paroxysmal nocturnal hemoglobinuria.
Atypical hemolytic uremic syndrome is related to a combination of genetic and environmental factors. Mutations lead to uncontrolled activation of the complement system (a part of the immune system that enhances the body's ability to fight pathogens), which then attacks the cells in the blood vessels of the kidneys, producing inflammation and the formation of abnormal clots and leading in some cases to kidney failure. Implicated environmental factors include exposure to some cancer drugs, chronic diseases, infections, cancers, organ transplantation, and pregnancy. Patients without known genetic or environmental causes of the condition are considered to have idiopathic atypical hemolytic uremic syndrome.
Eculizumab is a monoclonal antibody that specifically targets and inhibits the complement complex that produces thrombotic microangiopathy seen in atypical hemolytic uremic syndrome. It's the only approved treatment for atypical hemolytic uremic syndrome; the current standard treatment, plasma exchange or fresh frozen plasma infusion, hasn't been studied in controlled clinical trials. Eculizumab was found (in two small single-arm trials and one retrospective study) to improve platelet counts and to improve kidney function, eliminating in some cases the need for dialysis. Eculizumab shouldn't be used in the treatment of typical hemolytic uremic syndrome. A slightly different form of the disease, typical hemolytic uremic syndrome is a serious complication of a Shiga toxin–producing Escherichia coli bacterial infection. Typical hemolytic uremic syndrome is less likely than the atypical form to induce the recurrent attacks on the kidneys that lead to renal failure.
Common adverse effects of eculizumab are hypertension, diarrhea, headache, anemia, vomiting, nausea, upper respiratory infection, urinary tract infection, and leukopenia. An increased risk of life-threatening meningococcal infection is noted in a black-box warning on the drug label. Eculizumab has always had restrictions on its use because of this, and these restrictions will apply to the new indication. Prescribers must enroll in a registration program prior to prescribing the drug, and they must give the accompanying medication guide to patients who receive the drug.
Nurses who administer eculizumab should confirm that the patient was vaccinated against meningococcal infection at least two weeks before receiving the first dose of eculizumab; vaccination will reduce—but not eliminate—the risk of meningococcal infection. Patients require revaccination according to medical guidelines (see the Centers for Disease Control and Prevention [CDC] recommendations for adults at http://1.usa.gov/edOOqc and those for adolescents at http://1.usa.gov/cOFsKH).
Patient education should include the signs and symptoms of meningococcal infection (headache with nausea or vomiting, headache with a fever, headache with stiff neck or stiff back, a fever of 103°F [39.4°C] or higher, fever and a rash, confusion, muscle aches with flu-like symptoms, and sensitivity to light). Children taking eculizumab should be vaccinated against Streptococcus pneumoniae and Haemophilus influenzae type b according to current medical guidelines to prevent these infections. (See the CDC vaccination schedule for pediatric patients seven through 18 years of age at http://1.usa.gov/qeKvWk.)