Critical appraisal of eculizumab for atypical hemolytic uremic syndrome

Abstract

The biology of atypical hemolytic uremic syndrome has been shown to involve inability to limit activation of the alternative complement pathway, with subsequent damage to systemic endothelial beds and the vasculature, resulting in the prototypic findings of a thrombotic microangiopathy. Central to this process is the formation of the terminal membrane attack complex C5b-9. Recently, application of a monoclonal antibody that specifically binds to C5, eculizumab, became available to treat patients with atypical hemolytic uremic syndrome, replacing plasma exchange or infusion as primary therapy. This review focuses on the evidence, based on published clinical trials, case series, and case reports, on the efficacy and safety of this approach.

Monoclonal IgG4/2κ Deposition Following Eculizumab Therapy for Recurrent Atypical Hemolytic Uremic Syndrome in Kidney Transplantation

“…Thrombotic microangiopathy (TMA) is a clinical syndrome that manifests with microangiopathic hemolytic anemia, thrombocytopenia, and end-organ damage secondary to arteriolar and capillary microthrombi and endothelial injury. 1 Atypical hemolytic uremic syndrome (aHUS) is a rare form of TMA caused by overactivity of the alternative pathway of complement, with high rates of morbidity and mortality. 1 Genetic anomalies in the alternative pathway of complement are seen in 60% of cases of aHUS and are responsible for excessive complement activation.…”

Evaluation of health-related quality of life in hemolytic uraemic syndrome patients treated with eculizumab: a systematic evaluation on basis of EMPRO

“…Improving HRQoL should be considered while utilizing costly medications as a treatment option for prolonging life for a short length of time [ 47 ]. Eculizumab, a monoclonal antibody that specifically binds to C5 has been widely used worldwide for the treatment of aHUS [ 48 ]. The present study demonstrates that treatment with the eculizumab significantly improves HRQoL in patients with aHUS [ 27–29 , 41–46 ].…”

“…To the best of our knowledge, only two reviews have reported the data of HRQoL in aHUS population [ 48 , 50 ]. However, none of the studies reported the performance of patient self-reported HRQoL instruments applicable for aHUS patients.…”

Long-term outcomes of the Atypical Hemolytic Uremic Syndrome after kidney transplantation treated with eculizumab as first choice

“…Eculizumab, a terminal complement inhibitor, is approved for the treatment of aHUS to control the thrombotic microangiopathy (TMA) manifestations and to avoid the relapses of the disease. In the post-kidney transplantation, many studies have already described the same effect [ 20 , 21 ]. However, long-term studies combining eculizumab to immunosuppressive agents used in post-kidney transplantation are lacking[ 22 ].…”