A systematic review of eculizumab for atypical haemolytic uraemic syndrome (aHUS)

Abstract

ObjectiveTo determine the efficacy and safety of eculizumab for patients with atypical haemolytic uraemic syndrome (aHUS), compared with current treatment options.DesignA systematic review was performed according to the general principles of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. All study designs were included, except case histories.ParticipantsAll patients diagnosed with aHUS were included; no age restrictions were used.InterventionsEculizumab compared with current treatment options.Identification of studies12 databases were searched. Additional searches were performed through the Food and Drug Administration (FDA) and the Electronic Medicines Compendium websites, Google internet searches and contacting clinical experts. Reference lists of relevant articles were checked for additional studies.Results2 small, uncontrolled prospective multinational, multicentre studies and one small uncontrolled multinational, multicentre retrospective study were included. No meta-analyses were performed. Compared with baseline measures, thrombotic microangiopathy event-free status was achieved in 84% of patients in the prospective studies. Adverse events, as documented by enrolling investigators were frequent, with upper-respiratory tract infection affecting a third of patients. No deaths or episodes of meningitis or meningococcal septicaemia occurred in the prospective studies. Results of the study extension phases up to 114 weeks indicate that the benefits of the treatment are sustained.ConclusionsEculizumab is clinically effective for the treatment of aHUS. Further research is needed to evaluate eculizumab, ideally using patient-related clinical outcomes. If randomised studies are not feasible, study investigators should ensure that the threat of bias is minimised in future studies of eculizumab with respect to the reporting of patient recruitment and selection.

Case Report: Benefits and Challenges of Long-term Eculizumab in Atypical Hemolytic Uremic Syndrome

“…Case reports have been published with follow-up ranging from 1 to 3 years from initiation of treatment. 11,14 Respiratory tract infections, hypertension, and gastrointestinal disturbances are the most common adverse events reported, 16 and meningococcal septicemia has been described. 16,17 Administration of eculizumab in immunosuppressed patients may be complicated by meningococcal disease despite previous vaccination, 17 as described in our patient.…”

“…11,14 Respiratory tract infections, hypertension, and gastrointestinal disturbances are the most common adverse events reported, 16 and meningococcal septicemia has been described. 16,17 Administration of eculizumab in immunosuppressed patients may be complicated by meningococcal disease despite previous vaccination, 17 as described in our patient. The bactericidal efficiency of the immune response is unknown in patients with complement deficiencies or under complement blockade, and the effectiveness of antibiotic prophylaxis may become problematic with the emergence of resistant strains going forward.…”

“…A systematic review article identified only 3 small uncontrolled studies indicating that eculizumab is effective in patients with aHUS, with a reduction in frequency of thrombotic microangiopathy events. 16 Data on the safety profile of eculizumab in aHUS are limited. The safety record in the short term is reassuring, with no cumulative toxicity noted.…”

Protecting the kidney from complement: atypical haemolytic uraemic syndrome

“…NHS England's economic analysis suggests that the discounted incremental cost-effectiveness ratio for eculizumab, versus standard care, is around £521,000 per QALY gained for a 23-year-old cohort. 29 …”

Characterization of a New DGKE Intronic Mutation in Genetically Unsolved Cases of Familial Atypical Hemolytic Uremic Syndrome

“…Extensive studies showed that hyperactivation of the complement alternative pathway is the main pathogenetic effector mechanism leading to endothelial damage and microvascular thrombosis in most patients with aHUS (1,2 (1)(2)(3)(4)(5)(6)(7)(8)(9)(10). These findings paved the way for complement-tailored treatments (1,11) that have led to impressive improvements in short-and long-term prognosis (12). However, the underlying cause remains elusive for a substantial proportion of patients.…”