Terminal Complement Inhibitor Eculizumab in Atypical Hemolytic–Uremic Syndrome

Legendre, Christophe; Licht, Christoph; Muus, Petra; Greenbaum, Larry A.; Babu, Sunil; Bedrosian, Camille L.; Bingham, Coralie; Cohen, Daniëlle; Delmas, Yahsou; Douglas, K.; Eitner, Frank; Feldkamp, Thorsten; Fouque, Denis; Furman, Richard R.; Gaber, Osama; Herthelius, Maria; Hourmant, Maryvonne; Karpman, Diana; Lebranchu, Yvon; Mariat, Christophe; Menne, Jan; Moulin, Anne‐Marie; Nürnberger, Jens; Ogawa, Masayo; Remuzzi, Giuseppe; Richard, T; Sberro-Soussan, Rébecca; Severino, Beth; Sheerin, NS; Trivelli, Antonella; Zimmerhackl, Lothar Bernd; Goodship, Tim; Loirat, Chantal

doi:10.1056/nejmoa1208981

Cited by 1,340 publications

(1,335 citation statements)

References 34 publications

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“…Patients may develop end-stage renal failure either during the first episode or after several recurrences and the disease may recur after renal transplantation. Patients were previously exclusively treated with plasma exchange or infusions but the prognosis regarding renal function and mortality was poor until the introduction of eculizumab, which was shown to be highly effective in both adults and children with aHUS [24,25]. Current international consensus (2015) recommends the start of eculizumab treatment upon diagnosis of aHUS, although treatment can be discontinued in a small subset of patients, particularly those with autoantibodies [23].…”

Section: Treatment Of Atypical Hemolytic Uremic Syndromementioning

confidence: 99%

Orphan drug policies and use in pediatric nephrology

Karpman

Höglund

2016

Pediatr Nephrol

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Orphan drugs designed to treat rare diseases are often overpriced per patient. Novel treatments are sometimes even more expensive for patients with ultra-rare diseases, in part due to the limited number of patients. Pharmaceutical companies that develop a patented life-saving drug are in a position to charge a very high price, which, at best, may enable these companies to further develop drugs for use in rare disease. However, is there a limit to how much a life-saving drug should cost annually per patient? Government interventions and regulations may opt to withhold a life-saving drug solely due to its high price and cost-effectiveness. Processes related to drug pricing, reimbursement, and thereby availability, vary between countries, thus having implications on patient care. These processes are discussed, with specific focus on three drugs used in pediatric nephrology: agalsidase beta (for Fabry disease), eculizumab (for atypical hemolytic uremic syndrome), and cysteamine bitartrate (for cystinosis). Access to and costs of orphan drugs have most profound implications for patients, but also for their physicians, hospitals, insurance policies, and society at large, particularly from financial and ethical standpoints.

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Section: Treatment Of Atypical Hemolytic Uremic Syndromementioning

confidence: 99%

Orphan drug policies and use in pediatric nephrology

Karpman

Höglund

2016

Pediatr Nephrol

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“…10 Eculizumab is a first-in-class complement inhibitor and a humanized monoclonal antibody that binds to C5, thereby inhibiting the formation of the terminal components of the complement cascade. Recently, the use of eculizumab in pediatric patients with HCT-TMA has been reported.…”

mentioning

confidence: 99%

Eculizumab therapy in adults with allogeneic hematopoietic cell transplant-associated thrombotic microangiopathy

Vasu

Satoskar

et al. 2016

Bone Marrow Transplant

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“…No cumulative toxicity or unexpected serious infection-related adverse events, were observed through the trial period or the extension phase and survival was 100% in the studies [58,61]. However, there were two cases of meningococcal infections that were resolved with antibiotic treatment [61].…”

Section: Treatment Treatment Of Ahusmentioning

confidence: 94%

“…Eculizumab is a monoclonal antibody that binds with high affinity to complement protein C5, blocking the formation of the C5b-9 cell membrane attack complex, leaving proximal functions (opsonisation and immune clearance) intact. Two pivotal prospective studies in a total of 37 patients with aHUS have shown that administration of eculizumab produces a rapid and sustained inhibition of the TMA process, with significant improvements in clinical outcomes (haemolysis, long-term platelet counts and renal function), and discontinuation of plasma management and a 80% reduction in need for dialysis [58].…”

Section: Treatment Treatment Of Ahusmentioning

confidence: 99%

Atypical hemolytic uremic syndrome: from diagnosis to treatment

Franchini¹

2015

Clinical Chemistry and Laboratory Medicine (CCLM)

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Thrombotic microangiopathy (TMA) is a relatively rare condition but a medical urgency requiring immediate intervention to avoid irreversible organ damage or death. Symptoms on presentation include microangiopathic haemolytic anaemia, thrombocytopenia and organ damage. The most frequent direct causes of TMA are thrombotic thrombocytopenic purpura (TTP) and haemolytic uremic syndrome (HUS). The most common form of HUS is related to Shiga toxin producing Escherichia coli (STEC) infection while approximately 10% of cases are due to dysregulation of the complement pathway (atypical haemolytic uremic syndrome, aHUS). Optimal treatment regimens differ depending on the underlying cause; however, differential diagnosis may be difficult. The most accurate method of diagnosis is based on exclusion and should consider, beyond the symptoms common to TMA, ADAMTS13 activity levels and STEC infection status. For the management of TTP, plasma exchange (PE) is the most important acute intervention and is associated with lower mortality and better outcomes than plasma infusion. In most patients with STEC-HUS, the course of disease is selflimiting although management of acute kidney injury is often required. Until recently, the management of aHUS consisted of early and intensive PE, although this was mostly ineffective in protecting from subsequent organ damage. Eculizumab, an inhibitor of the alternative complement pathway, produces a rapid and sustained inhibition of the TMA process, with significant improvements in long-term clinical outcomes. Due to the significant improvement achieved, eculizumab has subsequently been approved as first-line therapy when an unequivocal diagnosis of aHUS has been made.

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Terminal Complement Inhibitor Eculizumab in Atypical Hemolytic–Uremic Syndrome

Cited by 1,340 publications

References 34 publications

Orphan drug policies and use in pediatric nephrology

Orphan drug policies and use in pediatric nephrology

Eculizumab therapy in adults with allogeneic hematopoietic cell transplant-associated thrombotic microangiopathy

Atypical hemolytic uremic syndrome: from diagnosis to treatment

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