Terminal Complement Inhibitor Eculizumab in Adult Patients With Atypical Hemolytic Uremic Syndrome: A Single-Arm, Open-Label Trial

Fakhouri, Fádi; Hourmant, Maryvonne; Campistol, Josep M.; Cataland, Spero R.; Espinosa, Mario; Gaber, A. Osama; Menne, Jan; Minetti, Enrico; François, Patrice; Rondeau, Éric; Ruggenenti, Piero; Weekers, Laurent; Ogawa, Masayo; Bedrosian, Camille L.; Legendre, Christophe

doi:10.1053/j.ajkd.2015.12.034

Cited by 244 publications

(262 citation statements)

References 25 publications

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“…The efficacy of eculizumab has been demonstrated in three prospective clinical trials performed primarily in adult patients with TMA [14, 20, 21]. In these trials, it was demonstrated that eculizumab resulted in a time-dependent improvement in patients with aHUS, and the beneficial effects were maintained after 2 years of follow-up.…”

Section: Discussionmentioning

confidence: 99%

Turkish pediatric atypical hemolytic uremic syndrome registry: initial analysis of 146 patients

et al. 2017

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BackgroundAtypical hemolytic uremic syndrome (aHUS) is a devastating disease with significant morbidity and mortality. Its genetic heterogeneity impacts its clinical presentation, progress, and outcome, and there is no consensus on its clinical management.MethodsTo identify the characteristics of aHUS in Turkish children, an industry-independent registry was established for data collection that includes both retrospective and prospective patients.ResultsIn total, 146 patients (62 boys, 84 girls) were enrolled; 53 patients (36.3%) were less than 2 years old at initial presentation. Among the 42 patients (37.1%) whose mutation screening was complete for CFH, CFI, MCP, CFB, C3, DGKE, and CHFR5 genes, underlying genetic abnormalities were uncovered in 34 patients (80.9%). Sixty-one patients (41.7%) had extrarenal involvement. During the acute stage, 33 patients (22.6%) received plasma therapy alone, among them 17 patients (51.5%) required dialysis, and 4 patients (12.1%) were still on dialysis at the time of discharge. In total, 103 patients (70.5%) received eculizumab therapy, 16 of whom (15.5%) received eculizumab as a first-line therapy. Plasma therapy was administered to 84.5% of the patients prior to eculizumab. In this group, renal replacement therapy was administered to 80 patients (77.7%) during the acute period. A total of 3 patients died during the acute stage. A total of 101 patients (77.7%) had a glomerular filtration rate >90 mL/min/1.73 m2 at the 2-year follow-up.ConclusionsThe Turkish aHUS registry will increase our knowledge of patients with aHUS who have different genetic backgrounds and will enable evaluation of the different treatment options and outcomes.

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Section: Discussionmentioning

confidence: 99%

Turkish pediatric atypical hemolytic uremic syndrome registry: initial analysis of 146 patients

et al. 2017

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“…Although these were single-arm studies rather than randomized, controlled trials, the historically poor outcomes (up to 77% of patients with CFH mutations had died or reached ESRD by 3-5 years) justified such study designs (27,28). These findings have been replicated in subsequent extension studies (29), prospective (nonrandomized) studies (30,31), and cohort analysis (32). In the prospective trials, complete TMA response was achieved in approximately 65% after 26 weeks of eculizumab therapy in both adults (26) and children (31).…”

Section: Complement-inhibiting Therapymentioning

confidence: 99%

Thrombotic Microangiopathy and the Kidney

Brocklebank

Wood

Kavanagh

2017

CJASN

261

288

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Thrombotic microangiopathy can manifest in a diverse range of diseases and is characterized by thrombocytopenia, microangiopathic hemolytic anemia, and organ injury, including AKI. It can be associated with significant morbidity and mortality, but a systematic approach to investigation and prompt initiation of supportive management and, in some cases, effective specific treatment can result in good outcomes. This review considers the classification, pathology, epidemiology, characteristics, and pathogenesis of the thrombotic microangiopathies, and outlines a pragmatic approach to diagnosis and management.

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“…As delays in eculizumab initiation in aHUS were associated with inferior renal function, a targeted approach of early initiation may minimize long-term renal impairment and maximize independence from dialysis. 4 We favor an approach incorporating early eculizumab initiation, continued therapy until patients achieve remission, and then a trial of cessation with regular monitoring. Given the potential risks of eculizumab therapy and its costs, most patients may benefit from a cessation trial when their underlying precipitant illness resolves and/or organ function has improved, but patient adherence is necessary.…”

mentioning

confidence: 99%

Eculizumab cessation in atypical hemolytic uremic syndrome

Merrill¹,

Brittingham²,

Yuan³

et al. 2017

Blood

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Terminal Complement Inhibitor Eculizumab in Adult Patients With Atypical Hemolytic Uremic Syndrome: A Single-Arm, Open-Label Trial

Abstract: Results highlight the benefits of eculizumab in adult patients with aHUS: improvement in hematologic, renal, and quality-of-life parameters; dialysis discontinuation; and transplant protection.

Cited by 244 publications

References 25 publications

Turkish pediatric atypical hemolytic uremic syndrome registry: initial analysis of 146 patients

Turkish pediatric atypical hemolytic uremic syndrome registry: initial analysis of 146 patients

Thrombotic Microangiopathy and the Kidney

Eculizumab cessation in atypical hemolytic uremic syndrome

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