Eculizumab is a safe and effective treatment in pediatric patients with atypical hemolytic uremic syndrome

Atypical hemolytic uremic syndrome (aHUS) is caused by alternative complement pathway dysregulation, leading to systemic thrombotic microangiopathy (TMA) and severe end-organ damage. Based on 2 prospective studies in mostly adults and retrospective data in children, eculizumab, a terminal complement inhibitor, is approved for aHUS treatment. Here we prospectively evaluated efficacy and safety of weight-based dosing of eculizumab in eligible pediatric patients with aHUS in an open-label phase II study. The primary end point was complete TMA response by 26 weeks. Twenty-two patients (aged 5 months–17 years) were treated; 16 were newly diagnosed, 12 had no prior plasma exchange/infusion during current TMA symptomatology, 11 received baseline dialysis, and 2 had prior renal transplants. By week 26, 14 achieved a complete TMA response, 18 achieved hematologic normalization, and 16 had 25% or better improvement in serum creatinine. Plasma exchange/infusion was discontinued in all, and 9 of the 11 patients who required dialysis at baseline discontinued, whereas none initiated new dialysis. Eculizumab was well tolerated; no deaths or meningococcal infections occurred. Bone marrow failure, wrist fracture, and acute respiratory failure were reported as unrelated severe adverse events. Thus, our findings establish the efficacy and safety of eculizumab for pediatric patients with aHUS and are consistent with proposed immediate eculizumab initiation following diagnosis in children. Atypical hemolytic uremic syndrome (aHUS) is caused by alternative complement pathway dysregulation, leading to systemic thrombotic microangiopathy (TMA) and severe end-organ damage. Based on 2 prospective studies in mostly adults and retrospective data in children, eculizumab, a terminal complement inhibitor, is approved for aHUS treatment. Here we prospectively evaluated efficacy and safety of weight-based dosing of eculizumab in eligible pediatric patients with aHUS in an open-label phase II study. The primary end point was complete TMA response by 26 weeks. Twenty-two patients (aged 5 months–17 years) were treated; 16 were newly diagnosed, 12 had no prior plasma exchange/infusion during current TMA symptomatology, 11 received baseline dialysis, and 2 had prior renal transplants. By week 26, 14 achieved a complete TMA response, 18 achieved hematologic normalization, and 16 had 25% or better improvement in serum creatinine. Plasma exchange/infusion was discontinued in all, and 9 of the 11 patients who required dialysis at baseline discontinued, whereas none initiated new dialysis. Eculizumab was well tolerated; no deaths or meningococcal infections occurred. Bone marrow failure, wrist fracture, and acute respiratory failure were reported as unrelated severe adverse events. Thus, our findings establish the efficacy and safety of eculizumab for pediatric patients with aHUS and are consistent with proposed immediate eculizumab initiation following diagnosis in children. Atypical hemolytic uremic syndrome (aHUS) is a progressive life-threatening thrombotic microangiopathy (TMA) associated with dysregulation of the complement alternative pathway.1Noris M. Remuzzi G. Atypical hemolytic–uremic syndrome.N Engl J Med. 2009; 361: 1676-1687Crossref PubMed Scopus (928) Google Scholar, 2Zipfel P.F. Heinen S. Skerka C. Thrombotic microangiopathies: new insights and new challenges.Curr Opin Nephrol Hypertens. 2010; 19: 372-378Crossref PubMed Scopus (42) Google Scholar, 3Benz K. Amann K. Thrombotic microangiopathy: new insights.Curr Opin Nephrol Hypertens. 2010; 19: 242-247Crossref PubMed Scopus (72) Google Scholar Complement gene mutations (e.g., complement factor H [CFH], membrane cofactor protein [MCP], complement factor I [CFI], complement factor B [CFB], complement protein 3 [C3]), or factor H autoantibodies are identified in 50% to 60% of patients with aHUS.4Noris M. Caprioli J. Bresin E. et al.Relative role of genetic complement abnormalities in sporadic and familial aHUS and their impact on clinical phenotype.Clin J Am Soc Nephrol. 2010; 5: 1844-1859Crossref PubMed Scopus (698) Google Scholar, 5Fremeaux–Bacchi V. Fakhouri F. Garnier A. et al.Genetics and outcome of atypical hemolytic uremic syndrome: a nationwide French series comparing children and adults.Clin J Am Soc Nephrol. 2013; 8: 554-562Crossref PubMed Scopus (481) Google Scholar, 6Maga T.K. Nishimura C.J. Weaver A.E. et al.Mutations in alternative pathway complement proteins in American patients with atypical hemolytic uremic syndrome.Hum Mutat. 2010; 31: E1445-E1460Crossref PubMed Scopus (226) Google Scholar Abnormalities in genes encoding thrombomodulin, plasminogen, and diacylglycerol kinase ε (DGKE)7Delvaeye M. Noris M. De Vriese A. et al.Thrombomodulin mutations in atypical hemolytic-uremic syndrome.N Engl J Med. 2009; 361: 345-357Crossref PubMed Scopus (419) Google Scholar, 8Bu F. Maga T. Meyer N.C. et al.Comprehensive genetic analysis of complement and coagulation genes in atypical hemolytic uremic syndrome.J Am Soc Nephrol. 2014; 25: 55-64Crossref PubMed Scopus (160) Google Scholar, 9Lemaire M. Fremeaux-Bacchi V. Schaefer F. et al.Recessive mutations in DGKE cause atypical hemolytic-uremic syndrome.Nat Genet. 2013; 45: 531-536Crossref PubMed Scopus (341) Google Scholar occur in a small number of patients. Evidence of a genetic abnormality is not required for diagnosis.4Noris M. Caprioli J. Bresin E. et al.Relative role of genetic complement abnormalities in sporadic and familial aHUS and their impact on clinical phenotype.Clin J Am Soc Nephrol. 2010; 5: 1844-1859Crossref PubMed Scopus (698) Google Scholar, 10Caprioli J. Noris M. Brioschi S. et al.Genetics of HUS: the impact of MCP, CFH, and IF mutations on clinical presentation, response to treatment, and outcome.Blood. 2006; 108: 1267-1279Crossref PubMed Scopus (561) Google Scholar, 11Sellier-Leclerc A.L. Fremeaux-Bacchi V. Dragon-Durey M.A. et al.Differential impact of complement mutations on clinical characteristics in atypical hemolytic uremic syndrome.J Am Soc Nephrol. 2007; 18: 2392-2400Crossref PubMed Scopus (310) Google Scholar, 12Loirat C. Noris M. Fremeaux-Bacchi V. Complement and the atypical hemolytic uremic syndrome in children.Pediatr Nephrol. 2008; 23: 1957-1972Crossref PubMed Scopus (170) Google Scholar, 13Zuber J. Fakhouri F. Roumenina L.T. et al.Use of eculizumab for atypical haemolytic uraemic syndrome and C3 glomerulopathies.Nat Rev Nephrol. 2012; 8: 643-657Crossref PubMed Scopus (390) Google Scholar Although onset may occur at any age, 40% of patients develop aHUS by 18 years of age.1Noris M. Remuzzi G. Atypical hemolytic–uremic syndrome.N Engl J Med. 2009; 361: 1676-1687Crossref PubMed Scopus (928) Google Scholar, 2Zipfel P.F. Heinen S. Skerka C. Thrombotic microangiopathies: new insights and new challenges.Curr Opin Nephrol Hypertens. 2010; 19: 372-378Crossref PubMed Scopus (42) Google Scholar, 5Fremeaux–Bacchi V. Fakhouri F. Garnier A. et al.Genetics and outcome of atypical hemolytic uremic syndrome: a nationwide French series comparing children and adults.Clin J Am Soc Nephrol. 2013; 8: 554-562Crossref PubMed Scopus (481) Google Scholar Clinical manifestations in children generally include anemia, thrombocytopenia, and acute kidney injury,5Fremeaux–Bacchi V. Fakhouri F. Garnier A. et al.Genetics and outcome of atypical hemolytic uremic syndrome: a nationwide French series comparing children and adults.Clin J Am Soc Nephrol. 2013; 8: 554-562Crossref PubMed Scopus (481) Google Scholar but peripheral gangrene,14Malina M. Gulati A. Bagga A. et al.Peripheral gangrene in children with atypical hemolytic uremic syndrome.Pediatrics. 2013; 131: e331-e335Crossref PubMed Scopus (40) Google Scholar arterial stenoses,15Loirat C. Macher M.A. Elmaleh-Berges M. et al.Non-atheromatous arterial stenoses in atypical haemolytic uraemic syndrome associated with complement dysregulation.Nephrol Dial Transplant. 2010; 25: 3421-3425Crossref PubMed Scopus (26) Google Scholar dilated cardiomyopathy, cardiorespiratory arrest,16Vilalta R. Lara E. Madrid A. et al.Long-term eculizumab improves clinical outcomes in atypical hemolytic uremic syndrome.Pediatr Nephrol. 2012; 27: 2323-2326Crossref PubMed Scopus (40) Google Scholar and neurologic,5Fremeaux–Bacchi V. Fakhouri F. Garnier A. et al.Genetics and outcome of atypical hemolytic uremic syndrome: a nationwide French series comparing children and adults.Clin J Am Soc Nephrol. 2013; 8: 554-562Crossref PubMed Scopus (481) Google Scholar, 17Dragon-Durey M.A. Sethi S.K. Bagga A. et al.Clinical features of anti-factor H autoantibody-associated hemolytic uremic syndrome.J Am Soc Nephrol. 2010; 21: 2180-2187Crossref PubMed Scopus (202) Google Scholar pulmonary,11Sellier-Leclerc A.L. Fremeaux-Bacchi V. Dragon-Durey M.A. et al.Differential impact of complement mutations on clinical characteristics in atypical hemolytic uremic syndrome.J Am Soc Nephrol. 2007; 18: 2392-2400Crossref PubMed Scopus (310) Google Scholar and gastrointestinal complications17Dragon-Durey M.A. Sethi S.K. Bagga A. et al.Clinical features of anti-factor H autoantibody-associated hemolytic uremic syndrome.J Am Soc Nephrol. 2010; 21: 2180-2187Crossref PubMed Scopus (202) Google Scholar have been reported. Historically, aHUS was managed with plasma exchange/plasma infusion (PE/PI) and was associated with high morbidity and mortality rates,1Noris M. Remuzzi G. Atypical hemolytic–uremic syndrome.N Engl J Med. 2009; 361: 1676-1687Crossref PubMed Scopus (928) Google Scholar, 2Zipfel P.F. Heinen S. Skerka C. Thrombotic microangiopathies: new insights and new challenges.Curr Opin Nephrol Hypertens. 2010; 19: 372-378Crossref PubMed Scopus (42) Google Scholar, 3Benz K. Amann K. Thrombotic microangiopathy: new insights.Curr Opin Nephrol Hypertens. 2010; 19: 242-247Crossref PubMed Scopus (72) Google Scholar, 5Fremeaux–Bacchi V. Fakhouri F. Garnier A. et al.Genetics and outcome of atypical hemolytic uremic syndrome: a nationwide French series comparing children and adults.Clin J Am Soc Nephrol. 2013; 8: 554-562Crossref PubMed Scopus (481) Google Scholar, 18Geerdink L.M. Westra D. van Wijk J.A. et al.Atypical hemolytic uremic syndrome in children: complement mutations and clinical characteristics.Pediatr Nephrol. 2012; 27: 1283-1291Crossref PubMed Scopus (110) Google Scholar with children having higher mortality than adults.5Fremeaux–Bacchi V. Fakhouri F. Garnier A. et al.Genetics and outcome of atypical hemolytic uremic syndrome: a nationwide French series comparing children and adults.Clin J Am Soc Nephrol. 2013; 8: 554-562Crossref PubMed Scopus (481) Google Scholar PE/PI may induce stabilization of hematologic parameters (but generally not significant renal function improvement),19Loirat C. Garnier A. Sellier-Leclerc A.L. et al.Plasmatherapy in atypical hemolytic uremic syndrome.Semin Thromb Hemost. 2010; 36: 673-681Crossref PubMed Scopus (73) Google Scholar is associated with complications, and impairs quality of life.19Loirat C. Garnier A. Sellier-Leclerc A.L. et al.Plasmatherapy in atypical hemolytic uremic syndrome.Semin Thromb Hemost. 2010; 36: 673-681Crossref PubMed Scopus (73) Google Scholar, 20Johnson S. Stojanovic J. Ariceta G. et al.An audit analysis of a guideline for the investigation and initial therapy of diarrhea negative (atypical) hemolytic uremic syndrome.Pediatr Nephrol. 2014; 29: 1967-1978Crossref PubMed Scopus (73) Google Scholar The availability of eculizumab (Soliris, Alexion Pharmaceuticals, Inc., Cheshire, CT, USA)21US Food and Drug Administration: Alexion Pharmaceuticals, Inc., Cheshire, Scholar, of Alexion an and the and approved therapy for and pediatric aHUS J. Fakhouri F. Roumenina L.T. et al.Use of eculizumab for atypical haemolytic uraemic syndrome and C3 glomerulopathies.Nat Rev Nephrol. 2012; 8: 643-657Crossref PubMed Scopus (390) Google Scholar, F. F. et the in clinical of eculizumab in patients with atypical hemolytic uremic syndrome the an analysis of J 2014; PubMed Scopus Google Scholar The efficacy and safety of eculizumab was in 2 prospective clinical of patients with and kidney C. et complement eculizumab in atypical hemolytic-uremic syndrome.N Engl J Med. 2013; PubMed Scopus Google Scholar, C. et and safety of eculizumab in atypical hemolytic uremic syndrome of phase 2 PubMed Scopus Google Scholar in children with aHUS is by J. Fakhouri F. Roumenina L.T. et al.Use of eculizumab for atypical haemolytic uraemic syndrome and C3 glomerulopathies.Nat Rev Nephrol. 2012; 8: 643-657Crossref PubMed Scopus (390) Google Scholar, R. Lara E. Madrid A. et al.Long-term eculizumab improves clinical outcomes in atypical hemolytic uremic syndrome.Pediatr Nephrol. 2012; 27: 2323-2326Crossref PubMed Scopus (40) Google Scholar, et in associated with C3 gene Nephrol. PubMed Scopus Google Scholar, A.L. Fremeaux-Bacchi V. of eculizumab in a with atypical hemolytic uremic syndrome.Pediatr Nephrol. PubMed Scopus Google Scholar, S. M. et in atypical hemolytic uremic syndrome: clinical and Nephrol. PubMed Scopus Google Scholar, et therapy in a with hemolytic uremic syndrome and Nephrol. 2012; 27: PubMed Scopus Google Scholar, van N.C. K. Eculizumab as therapy for atypical hemolytic uremic syndrome with Nephrol. 2012; 27: PubMed Scopus (26) Google Scholar, M. et in an with atypical haemolytic uraemic syndrome and Dial Transplant. 2013; PubMed Scopus Google Scholar, D. et onset atypical hemolytic uremic syndrome with Nephrol. 2013; PubMed Scopus Google Scholar, E. et therapy for atypical haemolytic uraemic syndrome to a of complement factor Nephrol. 2013; PubMed Scopus Google Scholar, K. K. et in atypical hemolytic uremic syndrome and with Nephrol. 2013; PubMed Scopus Google Scholar, E. S. et therapy for pediatric renal in aHUS with Nephrol. 2014; 29: PubMed Scopus (26) Google Scholar, Eculizumab for atypical hemolytic-uremic syndrome.N Engl J Med. 2009; PubMed Scopus Google Scholar, V. A. et of kidney function following with eculizumab and of plasma a kidney for atypical hemolytic uremic syndrome associated with a J 2010; PubMed Scopus Google Scholar and a retrospective D. R. et therapy for atypical hemolytic uremic syndrome in pediatric efficacy and safety outcomes a retrospective Scholar, R. S. J. et therapy for pediatric patients with atypical hemolytic uremic syndrome: efficacy and safety outcomes of a retrospective 2012; Google Scholar establish the efficacy and safety of eculizumab, a prospective clinical in patients with aHUS years was analysis 26 of are Twenty-two patients were with eculizumab, and the patients discontinued week were to eculizumab for a of in 5 to years age, years) was had identified complement gene abnormality or factor H had a DGKE patients years of had a of patients were newly patients received PE/PI at 18 patients had a baseline patients who had an patients were dialysis at baseline for a of and for during the current TMA patients had a of renal for renal and at to to to to or of complement gene or and and DGKE of the patients with aHUS onset at of and of were for DGKE aHUS diagnosis of current to PE/PI during current at who was dialysis at baseline and discontinued dialysis during the baseline the of renal than serum atypical hemolytic uremic CFH, complement factor complement factor diacylglycerol kinase MCP, membrane cofactor plasma of and and C3 of the patients with aHUS onset at of and of were for DGKE who was dialysis at baseline and discontinued dialysis during the baseline the of in a new atypical hemolytic uremic CFH, complement factor complement factor diacylglycerol kinase MCP, membrane cofactor plasma of end for the are in By week 26, 14 patients achieved the primary end point of complete TMA response a of of efficacy 26 of eculizumab end end point TMA outcome TMA outcomes improvement outcomes by (73) improvement by improvement by kidney thrombotic in a new kidney thrombotic TMA was achieved in patients baseline and 26 the TMA was to By PE/PI was discontinued in patients who required at was achieved in 18 patients a of patients achieved a of The who not a of eculizumab of a diagnosis of hemolytic uremic syndrome Eculizumab was associated with a and in baseline to The improvement in at was was achieved in 18 patients a of patients had an improvement in of in of eculizumab in in serum by in 16 patients a of patients had improvement of The improvement baseline to week in was patients with kidney had improvement of of 11 patients dialysis at baseline discontinued dialysis during the a of of discontinued dialysis eculizumab 11 patients not baseline dialysis dialysis patients were dialysis at week in of eculizumab in The efficacy of eculizumab was in patients with and identified complement abnormalities gene mutations or or factor H or TMA response was achieved in patients with and patients TMA was achieved by 11 patients and patients with and patients with and patients complement abnormalities for hematologic improvement in 11 patients and patients with and The with the identified DGKE discontinued dialysis at initiation of eculizumab and not dialysis during the study. achieved complete TMA response, TMA and hematologic by week 3 the baseline characteristics of patients who and who not for the primary end point at 26 weeks. The of patients who not complete TMA response had a of identified complement abnormalities with as well as renal function at of patients with baseline not complete TMA and characteristics of patients who and who not for the primary end point complete TMA not complete TMA at to to to to or of complement gene or identified complement gene or aHUS diagnosis of current to PE/PI during current at renal than the serum atypical hemolytic uremic CFH, complement factor complement factor MCP, membrane cofactor plasma of in a new atypical hemolytic uremic CFH, complement factor complement factor MCP, membrane cofactor plasma of who and who not complete TMA response had a of to eculizumab and received a of eculizumab and eculizumab The pediatric of baseline to week was and of of the were and was and consistent with C. et complement eculizumab in atypical hemolytic-uremic syndrome.N Engl J Med. 2013; PubMed Scopus Google Scholar The of eculizumab was were generally and were in the with during 18 patients with data had of complete terminal complement who for had a on and the had of an eculizumab of and of hemolytic The not have of the or of at any point during the The not complete TMA response, achieved hematologic the eculizumab not have improvement in or serum and was dialysis at baseline and 26 of and by the to week for the and the of to to to to 18 the to week for the and the of in a new adverse in patients were or in and the were and respiratory 3 in 2 patients who were to of and in who was 5 to years of were to marrow failure, wrist fracture, and acute respiratory Bone marrow failure was anemia, thrombocytopenia, and the of the and associated and were to aHUS and of a The reported the marrow failure as marrow the had a 3 during the marrow was not The was with and The of acute respiratory failure in a with and by a onset of respiratory required patients and on severe was to to patients reported of of to The with on eculizumab safety deaths or meningococcal infections adverse respiratory with to eculizumab, respiratory respiratory respiratory with any in 2 or respiratory adverse adverse respiratory respiratory respiratory in a new adverse adverse events. of and were in patients and patients had baseline and at with and patients had by week was for patients with the of The who discontinued the of the of had no identified complement abnormality and not have TMA of who the of a was not was are the prospective in patients with aHUS years of Eculizumab to complete TMA response in of patients 26 and the for in hematologic and renal Clinical were by the of PE/PI in patients and of dialysis in of patients who required at who not baseline dialysis not to renal or dialysis during treatment. were in patients with or identified genetic with an identified DGKE quality of 26 of The safety of eculizumab was consistent with studies in C. et complement eculizumab in atypical hemolytic-uremic syndrome.N Engl J Med. 2013; PubMed Scopus Google Scholar and no new safety were findings are consistent with prospective clinical of eculizumab in adults with aHUS and in and patients with a and C. et complement eculizumab in atypical hemolytic-uremic syndrome.N Engl J Med. 2013; PubMed Scopus Google Scholar, C. et and safety of eculizumab in atypical hemolytic uremic syndrome of phase 2 PubMed Scopus Google Scholar and in a retrospective of pediatric patients with Food and Drug Administration: Alexion Pharmaceuticals, Inc., Cheshire, Scholar of renal function is achieved eculizumab is as as aHUS C. et complement eculizumab in atypical hemolytic-uremic syndrome.N Engl J Med. 2013; PubMed Scopus Google Scholar, V. Fremeaux-Bacchi V. T. et and efficacy of eculizumab in a renal with atypical hemolytic-uremic J Transplant. 2009; PubMed Scopus Google Scholar, C.J. V. et eculizumab in atypical hemolytic uremic J Am Soc Nephrol. 2009; PubMed Scopus Google Scholar the current patients received eculizumab Although had and were dialysis at significant were as as week initiation of therapy and were the study. The and of renal improvement and of dialysis, is of children with aHUS to renal or managed with V. Fakhouri F. Garnier A. et al.Genetics and outcome of atypical hemolytic uremic syndrome: a nationwide French series comparing children and adults.Clin J Am Soc Nephrol. 2013; 8: 554-562Crossref PubMed Scopus (481) Google Scholar findings are consistent with a prospective of eculizumab in patients with F. M. et thrombotic microangiopathy (TMA) and improves renal function in atypical hemolytic uremic syndrome (aHUS) patients Am Soc Nephrol. 2013; Scholar analysis was to baseline may of hematologic and renal function as by the primary end point of complete TMA Although the small number is patients who not complete TMA response had a not having an identified complement gene and having renal function at studies are to the current of patients not Thus, in clinical C. et complement eculizumab in atypical hemolytic-uremic syndrome.N Engl J Med. 2013; PubMed Scopus Google Scholar and F. M. et thrombotic microangiopathy (TMA) and improves renal function in atypical hemolytic uremic syndrome (aHUS) patients Am Soc Nephrol. 2013; Scholar in to received PE/PI an with aHUS who received eculizumab, was well and to hematologic and renal function M. M. C. et as therapy for atypical hemolytic uremic syndrome.Pediatrics. 2014; PubMed Scopus Google Scholar findings to eculizumab of TMA and on clinical diagnosis of aHUS in pediatric patients to outcomes and to associated with J. Fakhouri F. Roumenina L.T. et al.Use of eculizumab for atypical haemolytic uraemic syndrome and C3 glomerulopathies.Nat Rev Nephrol. 2012; 8: 643-657Crossref PubMed Scopus (390) Google Scholar, M. Ariceta G. et al.An for atypical haemolytic uraemic syndrome: diagnosis and treatment. 2013; Google Scholar, C. Fakhouri F. Ariceta G. et al.An to the of atypical hemolytic uremic syndrome in children.Pediatr Nephrol. 31: PubMed Scopus Google Scholar the of eculizumab in a prospective clinical in children. the approved pediatric dosing in eculizumab of to for consistent with reported in the C. et complement eculizumab in atypical hemolytic-uremic syndrome.N Engl J Med. 2013; PubMed Scopus Google Scholar had of eculizumab of hemolytic at point during the and on dialysis but in the safety studies of eculizumab, were not in patients with aHUS and were in of patients with with clinical or Food and Drug Administration: Alexion Pharmaceuticals, Inc., Cheshire, Scholar clinical for in complement is during J. Fakhouri F. Roumenina L.T. et al.Use of eculizumab for atypical haemolytic uraemic syndrome and C3 glomerulopathies.Nat Rev Nephrol. 2012; 8: 643-657Crossref PubMed Scopus (390) Google Scholar was a of associated with eculizumab in a patients with S. et in pediatric Nephrol. PubMed Scopus Google Scholar the current were in patients and was a of eculizumab findings the and in patients eculizumab initiation may to TMA were and not associated with clinical no discontinued eculizumab of or was an open-label of may by the of a the of the primary end point of complete TMA response required improvement in serum patients who had hematologic but kidney The availability of eculizumab the for patients with prospective eculizumab TMA and is well in children. of and improvement of renal function during eculizumab the for an clinical The phase and a aHUS insights of eculizumab in children with patients to 18 years with an aHUS diagnosis who were at clinical and eligible patients had a than the of the than or to the of with a negative and serum for with or an identified complement gene or of were CFH, MCP, C3 and and was at was or negative for DGKE mutations in patients with onset at of and of of the of or severe a and with a PE/PI for dialysis for renal and of eculizumab or to patients were and 14 or initiation of or received 2 meningococcal to therapy years received treatment, at the was no for of was an open-label phase II clinical of eculizumab in patients years of with aHUS a a an of to 2 and a safety eculizumab who discontinued were at for to aHUS and Eculizumab was at by on with patients with and data to of patients had complete and terminal complement at of complement or and to the were by infusion to at the PE/PI was an eculizumab was of of eculizumab on to to to to 2 who required or plasma infusion received a of eculizumab eculizumab was or was in a new 2 weeks. who required or plasma infusion received a of eculizumab eculizumab was or was The primary was to the efficacy and safety of eculizumab in patients with aHUS years of to by thrombocytopenia, and renal The was approved by the at or by an and was in with the on and the of patients or or and The primary end point was the of patients who achieved complete TMA response, as hematologic than the and improvement in renal function in serum on 2 to complete TMA response was the eculizumab to the the was end TMA in no and no new the TMA number of PE/PI and new dialysis hematologic and than the in serum improvement in by and improvement in by was the A. et to in children with Am Soc Nephrol. 2009; PubMed Scopus Google as dialysis. end were required to for The in quality of baseline was the pediatric of for children to years of who complete the D. et for children with and of the pediatric of 2007; 29: PubMed Scopus Google Scholar and Scholar baseline in and of were at week of of analysis at week and clinical characteristics of of patients who and who not for the primary end point were evaluated in a and and for of eculizumab and of et of and and during PubMed Scopus Google Scholar were and to to dosing were and infusion were a and by and to to to to in a new Plasma eculizumab were to a to weight-based dosing of Scholar to parameters and The of was at to and to and to and to and and and eculizumab to and to of the 2 eculizumab were to the and were to a and at in the for 3 by and of with the a were in the as patients who received eculizumab was as the the eculizumab The baseline for dialysis was as 14 the eculizumab TMA response at week 26 was the end patients were at the data were were as end The of patients with improvement was to the primary end serum and were for efficacy end the primary end were at the for of parameters were during the the and phase at by and The number of patients to was on a to patients in of the following to to and 5 to was by Alexion Pharmaceuticals, is a and and Alexion Pharmaceuticals, is a and Alexion Pharmaceuticals, and Alexion Pharmaceuticals, and Alexion Pharmaceuticals, and and is a of the of and Alexion Pharmaceuticals, is a of the aHUS and the and Alexion Pharmaceuticals, is a of the and for and Alexion and and is on the for Alexion Pharmaceuticals, is by Alexion Pharmaceuticals, is by Alexion Pharmaceuticals, is a and and Alexion Pharmaceuticals, Alexion Pharmaceuticals, The no of the data in was as an at the of the American of was by and of by Alexion Pharmaceuticals, Inc., and by F. and of Alexion Pharmaceuticals, Eculizumab in children with hemolytic uremic et the prospective of eculizumab in pediatric atypical hemolytic uremic in eculizumab and no safety were reported. is the of a in response to with a outcome in complement had renal function at presentation, and to or et Eculizumab is a and in pediatric patients with atypical hemolytic uremic of the to D. and for their to the in of to the study.

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