Eculizumab in Anti-Factor H Antibodies Associated With Atypical Hemolytic Uremic Syndrome

Abstract

Atypical hemolytic uremic syndrome (aHUS) is a life-threatening multisystemic condition often leading to end-stage renal failure. It results from an increased activation of the alternative pathway of the complement system due to mutations of genes coding for inhibitors of this pathway or from autoantibodies directed against them. Eculizumab is a monoclonal antibody directed against complement component C5 and inhibiting the activation of the effector limb of the complement system. Its efficacy has already been demonstrated in aHUS. The present article reports for the first time the use of eculizumab in a patient presenting with aHUS associated with circulating anti-complement Factor H autoantibodies and complicated by cardiac and neurologic symptoms. Our observation highlights the efficacy of eculizumab in this form of aHUS not only on renal symptoms but also on the extrarenal symptoms. It also suggests that eculizumab should be used very promptly after aHUS presentation to prevent life-threatening complications and to reduce the risk of chronic disabilities. To obtain a complete inhibition of the effector limb activation, the advised dosage must be respected. After this initial therapy in the autoimmune aHUS form, a long-term immunosuppressive treatment should be considered, to prevent relapses by reducing anti-complement Factor H autoantibody plasma levels.

Factor H autoantibody is associated with atypical hemolytic uremic syndrome in children in the United Kingdom and Ireland

“…Successful use of the terminal complement inhibitor eculizumab in anti-FH autoantibody–associated aHUS has been reported in a small number of patients in trials 31 , 32 and case reports. 33 , 34 , 35 , 36 , 37 In our study, 6 patients were treated with and continue on eculizumab: 4 of 6 were started on eculizumab at the first presentation, 1 of 6 at relapse, and 1 of 6 following early recurrence after transplantation, with sustained remission observed in all; 3 patients have stable chronic kidney disease stage 3A, and 3 patients have an eGFR >60 ml/min per 1.73 m 2 . There have been no deaths in our cohort, and no adverse events associated with eculizumab.…”

Complement factor H antibody-associated atypical hemolytic uremic syndrome and eculizumab treatment

“…Bu tedavi ile hematolojik remisyonun sağlandığı ve klinik gidişin daha iyi olduğu gösterilmiştir (10) . Anti-FH antikoru olan aHUS tanılı hastalarda Ekulizumab kullanımı ile ilgili veriler oldukça sınırlı olmakla birlikte, etkisini gösteren yayınlar vardır (12,13) . 2016 yılında yayınla-nan uzlaşı raporunda, ilk atak aHUS'te Ekulizumabın başlanmasını, takipte anti-FH antikoru saptanması durumunda ekstrarenal organ tutulumunun şiddetli ise Ekulizumab ile birlikte plazma değişimi ve immunsupresif tedavi önerilmiştir (8) .…”

Case report of atypical hemolytic uremic syndrome with retinal arterial and venous occlusion treated with eculizumab

“…Effects of eculizumab on extrarenal manifestations of aHUS were not evaluated in the clinical trials. 13 – 16 However, case studies have demonstrated the effectiveness of eculizumab for resolution of confirmed or suspected neurologic, 28 , 31 – 36 cardiovascular, 29 – 31 , 34 , 35 , 37 peripheral vascular, 38 pulmonary, 30 , 34 , 36 gastrointestinal, 36 , 39 , 40 and skin 41 manifestations of the disease.…”