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Efficacy and Safety of Eculizumab in Pediatric Patients Affected by Shiga Toxin-Related Hemolytic and Uremic Syndrome: A Randomized, Placebo-Controlled Trial.

dc.rights.licenseauthentificationen_US
dc.contributor.authorGARNIER, Arnaud
dc.contributor.authorBROCHARD, Karine
dc.contributor.authorKWON, Theresa
dc.contributor.authorSELLIER-LECLERC, Anne-Laure
dc.contributor.authorLAHOCHE, Annie
dc.contributor.authorLAUNAY, Emma Allain
dc.contributor.authorNOBILI, François
dc.contributor.authorCAILLEZ, Mathilde
dc.contributor.authorTAQUE, Sophie
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorHARAMBAT, Jerome
dc.contributor.authorMICHEL-BOURDAT, Guylhene
dc.contributor.authorGUIGONIS, Vincent
dc.contributor.authorFILA, Marc
dc.contributor.authorCLOAREC, Sylvie
dc.contributor.authorDJAMAL-DINE, Djeddi
dc.contributor.authorDE PARSCAUX, Loïc
dc.contributor.authorALLARD, Lise
dc.contributor.authorSALOMON, Rémi
dc.contributor.authorULINSKI, Tim
dc.contributor.authorFRÉMEAUX-BACCHI, Véronique
dc.contributor.authorMORIN, Christophe
dc.contributor.authorOLIVIER-ABBAL, Pascale
dc.contributor.authorCOLINEAUX, Hélène
dc.contributor.authorAURIOL, Françoise
dc.contributor.authorARNAUD, Catherine
dc.contributor.authorKIEFFER, Isabelle
dc.contributor.authorBRUSQ, Clara
dc.date.accessioned2023-10-04T14:13:37Z
dc.date.available2023-10-04T14:13:37Z
dc.date.issued2023-09-01
dc.identifier.issn1533-3450en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/184326
dc.description.abstractEnShiga toxin-related hemolytic uremic syndrome (STEC-HUS) is a serious condition, characterized by multiorgan thrombotic microangiopathy, mainly affecting children. Renal involvement is severe, with approximately half of patients requiring dialysis. So far, no specific treatment has been proven efficient in STEC-HUS. The use of eculizumab, a monoclonal antibody inhibiting terminal complement complex, has demonstrated remarkable success in atypical hemolytic uremic syndrome, but its use in uncontrolled studies to treat STEC-HUS has yielded inconsistent results. In this Phase 3 randomized, placebo-controlled trial in 100 pediatric patients with STEC-HUS, the findings did not show efficacy of eculizumab during the acute phase of the disease. However, the results indicated a reduction of renal sequelae in eculizumab-treated patients at 1-year follow-up. Larger prospective studies would be needed to further explore eculizumab as a potential treatment. Shiga toxin-related hemolytic uremic syndrome (STEC-HUS) in children is a severe condition, resulting in approximately 50% of patients requiring RRT. Furthermore, at least 30% of survivors experience kidney sequelae. Recently, activation of the complement alternative pathway has been postulated as a factor in STEC-HUS pathophysiology, leading to compassionate use of eculizumab, a monoclonal antibody inhibiting the terminal complement complex, in affected patients. Given the lack of therapy for STEC-HUS, a controlled study of eculizumab efficacy in treating this condition is a priority. We conducted a Phase 3 randomized trial of eculizumab in children with STEC-HUS. Patients were randomly assigned in a 1:1 ratio to receive either eculizumab or placebo during 4 weeks. Follow-up lasted for 1 year. The primary end point was RRT duration <48 hours after randomization. Secondary endpoints included hematologic and extrarenal involvement. Baseline characteristics were similar among the 100 patients who underwent randomization. The rate of RRT <48 hours did not differ significantly between the two groups (48% in the placebo versus 38% in the eculizumab group; P = 0.31) or in the course of ARF. The two groups also exhibited similar hematologic evolution and extrarenal manifestations of STEC-HUS. The proportion of patients experiencing renal sequelae at 1 year was lower in the eculizumab group than in the placebo group (43.48% and 64.44%, respectively, P = 0.04). No safety concern was reported. In pediatric patients with STEC-HUS, eculizumab treatment does not appear to be associated with improved renal outcome during acute phase of the disease but may reduce long-term kidney sequelae. EUDRACT (2014-001169-28) ClinicalTrials.gov ( NCT02205541 ).
dc.language.isoENen_US
dc.subject.enChild
dc.subject.enHumans
dc.subject.enProspective Studies
dc.subject.enComplement Membrane Attack Complex
dc.subject.enShiga Toxin
dc.subject.enAntibodies
dc.subject.enMonoclonal
dc.subject.enHumanized
dc.subject.enAtypical Hemolytic Uremic Syndrome
dc.subject.enEscherichia coli Infections
dc.title.enEfficacy and Safety of Eculizumab in Pediatric Patients Affected by Shiga Toxin-Related Hemolytic and Uremic Syndrome: A Randomized, Placebo-Controlled Trial.
dc.title.alternativeJ Am Soc Nephrolen_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1681/asn.0000000000000182en_US
dc.subject.halSciences du Vivant [q-bio]/Santé publique et épidémiologieen_US
dc.identifier.pubmed37303085en_US
bordeaux.journalJournal of the American Society of Nephrology : JASNen_US
bordeaux.page1561-1573en_US
bordeaux.volume34en_US
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - UMR 1219en_US
bordeaux.issue9en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.teamLEHAen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.import.sourcepubmed
hal.identifierhal-04228613
hal.version1
hal.date.transferred2023-10-04T14:13:41Z
hal.popularnonen_US
hal.audienceInternationaleen_US
hal.exporttrue
workflow.import.sourcepubmed
dc.rights.ccPas de Licence CCen_US
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