Long-term eculizumab improves clinical outcomes in atypical hemolytic uremic syndrome

Vilalta, R.; Lara, Enrique; Madrid, Álvaro; Chocrón, Sara; Muñoz, Marina; Casquero, Amaia Gómez; Gálvez-Nieto, José Luis

doi:10.1007/s00467-012-2276-8

Cited by 53 publications

(34 citation statements)

References 9 publications

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“…That eculizumab may be efficacious to rescue central nervous system involvement is suggested by nine case reports, including four in children [87,90,110,[123][124][125][126][127]. Eculizumab also appeared lifesaving in four children with myocardial involvement [83,90,92,110]. The reports of four children who developed cerebral ischemic events due to stenosis of cerebral arteries after several years on dialysis have suggested that local complement activation added to the vascular consequences of long-term dialysis may lead to such macrovascular complications [101,[128][129][130].…”

Section: Education Information Cardmentioning

confidence: 93%

An international consensus approach to the management of atypical hemolytic uremic syndrome in children

et al. 2015

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Atypical hemolytic uremic syndrome (aHUS) emerged during the last decade as a disease largely of complement dysregulation. This advance facilitated the development of novel, rational treatment options targeting terminal complement activation, e.g., using an anti-C5 antibody (eculizumab). We review treatment and patient management issues related to this therapeutic approach. We present consensus clinical practice recommendations generated by HUS International, an international expert group of clinicians and basic scientists with a focused interest in HUS. We aim to address the following questions of high relevance to daily clinical practice: Which complement investigations should be done and when? What is the importance of anti-factor H antibody detection? Who should be treated with eculizumab? Is plasma exchange therapy still needed? When should eculizumab therapy be initiated? How and when should complement blockade be monitored? Can the approved treatment schedule be modified? What approach should be taken to kidney and/or combined liver-kidney transplantation? How should we limit the risk of meningococcal infection under complement blockade therapy? A pressing question today regards the treatment duration. We discuss the need for prospective studies to establish evidence-based criteria for the continuation or cessation of anticomplement therapy in patients with and without identified complement mutations.

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Section: Education Information Cardmentioning

confidence: 93%

An international consensus approach to the management of atypical hemolytic uremic syndrome in children

et al. 2015

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“…10 There are no randomized controlled trials examining the treatment of aHUS. There are small case reports and case series [11][12][13][14] and a prospective trial 15 of patients who were successfully treated with eculizumab. Evidence suggests that earlier treatment leads to greater improvement in renal function and reversal of target organ damage.…”

Section: Discussionmentioning

confidence: 99%

“…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.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2015

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Atypical hemolytic uremic syndrome (aHUS) is caused by dysregulation of the complement system, leading to complement overactivation. A humanized anti-C5 monoclonal antibody, eculizumab, has been available for the treatment of aHUS since 2011. The long-term safety and efficacy of this novel drug in the pediatric population remain under review. We present a child with a hybrid CFH/CFHR3 gene who, having had multiple disease relapses despite optimal treatment with plasma exchange, commenced eculizumab therapy in August 2010. She remains relapse free in follow-up at 52 months, and treatment has been well tolerated. The risk of meningococcal disease during this treatment is recognized. Despite vaccination against meningococcal disease and appropriate antibiotic prophylaxis, our patient developed meningococcal bacteremia 30 months into treatment. She presented with nonspecific symptoms but recovered without sequelae with appropriate treatment. We recommend that children be vaccinated against invasive meningococcal infection before beginning eculizumab therapy and take appropriate antibiotic prophylaxis during treatment, and we suggest that vaccine responses should be checked and followed annually. Clinicians need to maintain a high index of suspicion for invasive meningococcal disease. Neither vaccination nor antibiotic prophylaxis provides complete protection in patients on eculizumab therapy. The appropriate dosage of eculizumab needed to achieve remission in aHUS in the pediatric population is unknown. Having achieved remission in our patient, we monitor eculizumab and CH50 levels to evaluate ongoing blockade of the terminal complement cascade. Such information may help guide dosing intervals in the future.

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“…For atypisk hemolytisk uremisk syndrom er det ikke gjort randomiserte, placebokontrollerte studier, men det foreligger flere studier der effekt på endepunkter som nyrefunksjon og proteinuri er dokumentert (13,18). En rekke kasuistikker og serier med noen få pasienter har vist meget god effekt, noe som sammen med sykdommens sjeldne forekomst har lagt grunnlaget for myndighetenes godkjenning (19).…”

Section: Kontrollerte Kliniske Studierog Mangel På Slikeunclassified

Terapeutisk komplementhemming – fra eksperimentell til klinisk medisin

Lappegård¹,

Bjerre²,

Tjønnfjord³

et al. 2015

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Long-term eculizumab improves clinical outcomes in atypical hemolytic uremic syndrome

Abstract: Background Atypical hemolytic uremic syndrome (aHUS) is a rare genetic disorder caused by chronic uncontrolled complement activation.

Cited by 53 publications

References 9 publications

An international consensus approach to the management of atypical hemolytic uremic syndrome in children

An international consensus approach to the management of atypical hemolytic uremic syndrome in children

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

Terapeutisk komplementhemming – fra eksperimentell til klinisk medisin

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