Eculizumab for treating atypical haemolytic uraemic syndrome

Atypical haemolytic uraemic syndrome (aHUS) is a chronic, rare, progressive condition that causes severe inflammation of blood vessels and the formation of blood clots in small blood vessels throughout the body, a process known as systemic thrombotic microangiopathy. In around 70% of patients, aHUS is associated with an underlying genetic or acquired abnormality of the proteins of the complement system, which is part of the body's defence against infection. The prognosis for people with aHUS is poor. Patients are at constant risk of sudden and progressive damage, and failure of vital organs. Mortality rates range from 10–15% in the acute phase of the disease and, within a year of diagnosis, up to 70% of patients progress to end‑stage renal failure and need dialysis or die. One patient in 5 has aHUS affecting organs other than the kidneys, most commonly the brain or heart.

aHUS can occur at any age. Onset occurs in childhood more frequently than in adulthood (around 60% and 40% of all cases respectively). Most children (70%) who develop aHUS will experience the disease for the first time before the age of 2 years. The true incidence and prevalence of aHUS in England is uncertain because some patients remain undiagnosed. Worldwide, the prevalence of aHUS ranges from 2.7–5.5 per million population, with an incidence of about 0.40 per million population.

Before eculizumab became available, plasma therapy was traditionally the first‑line treatment for aHUS. Guidelines published by the British Committee for Standards in Haematology and the British Transplantation Society (2009; before the availability of eculizumab) recommend offering all patients with aHUS a trial of plasma exchange and/or plasma infusion. However, response to plasma therapy is variable, and up to 40% of patients may die or progress to end‑stage renal failure and need dialysis with the first clinical aHUS manifestation, despite the use of plasma therapy. Some patients may be eligible for a kidney or combined kidney–liver transplantation; however, there is a high risk of organ rejection after recurrent disease.