Eculizumab, a terminal complement inhibitor, improves anaemia in patients with paroxysmal nocturnal haemoglobinuria
Identifieur interne : 008D72 ( Main/Exploration ); précédent : 008D71; suivant : 008D73Eculizumab, a terminal complement inhibitor, improves anaemia in patients with paroxysmal nocturnal haemoglobinuria
Auteurs : Jörg Schubert [Allemagne] ; Peter Hillmen [Royaume-Uni] ; Alexander Röth [Allemagne] ; Neal S. Young [États-Unis] ; Modupe O. Elebute [Royaume-Uni] ; Jeffrey Szer [Australie] ; Giacomo Gianfaldoni [Italie] ; Gérard Socie [France] ; Paul Browne [Irlande (pays)] ; Robert Geller [États-Unis] ; Russell P. Rother [États-Unis] ; Petra Muus [Pays-Bas]Source :
- British journal of haematology [ 0007-1048 ] ; 2008.
Descripteurs français
- Pascal (Inist)
- Wicri :
- topic : Homme.
English descriptors
- KwdEn :
Abstract
In paroxysmal nocturnal haemoglobinuria (PNH), chronic destruction of PNH red blood cells (RBCs) by complement leads to anaemia and other serious morbidities. Eculizumab inhibits terminal complement-mediated PNH RBC destruction by targeting C5. In the phase III, double-blind, placebo-controlled, TRIUMPH study, eculizumab reduced haemolysis, stabilized haemoglobin levels, reduced transfusion requirements and improved fatigue in patients with PNH. Herein, we explored the effects of eculizumab on measures of anaemia in patients from the TRIUMPH study and the open-label SHEPHERD study, a more heterogeneous population. Eculizumab reduced haemolysis regardless of pretreatment transfusion requirements and regardless of whether or not patients became transfusion-dependent during treatment (P< 0.001). Reduction in haemolysis was associated with increased PNH RBC counts (P <0.001) while reticulocyte counts remained elevated. Eculizumab-treated patients demonstrated significantly higher levels of haemoglobin as compared with placebo in TRIUMPH and relative to baseline levels in SHEPHERD (P < 0.001 for each study). Eculizumab lowered transfusion requirement across multiple pretreatment transfusion strata and eliminated transfusion support in a majority of both TRIUMPH and SHEPHERD patients (P < 0-001). Patients who required some transfusion support during treatment with eculizumab showed a reduction in haemolysis and transfusion requirements and an improvement in fatigue. Eculizumab reduces haemolysis and improves anaemia and fatigue, regardless of transfusion requirements.
Affiliations:
- Allemagne, Australie, France, Irlande (pays), Italie, Pays-Bas, Royaume-Uni, États-Unis
- Angleterre, Grand Londres, Gueldre, Victoria (État), Île-de-France
- Londres, Melbourne, Nimègue, Paris
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Young</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Cell Biology Section, Clinical Hematology Branch, NHLBI, NIH</s1><s2>Bethesda, MD</s2><s3>USA</s3><sZ>4 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Bethesda, MD</wicri:noRegion></affiliation></author><author><name sortKey="Elebute, Modupe O" sort="Elebute, Modupe O" uniqKey="Elebute M" first="Modupe O." last="Elebute">Modupe O. Elebute</name><affiliation wicri:level="3"><inist:fA14 i1="05"><s1>Department of Cellular and Molecular Medicine, St. Georges Hospital</s1><s2>London</s2><s3>GBR</s3><sZ>5 aut.</sZ></inist:fA14><country>Royaume-Uni</country><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Szer, Jeffrey" sort="Szer, Jeffrey" uniqKey="Szer J" first="Jeffrey" last="Szer">Jeffrey Szer</name><affiliation wicri:level="3"><inist:fA14 i1="06"><s1>Department of Clinical Haematology, Royal Melbourne Hospital</s1><s2>Melbourne</s2><s3>AUS</s3><sZ>6 aut.</sZ></inist:fA14><country>Australie</country><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Gianfaldoni, Giacomo" sort="Gianfaldoni, Giacomo" uniqKey="Gianfaldoni G" first="Giacomo" last="Gianfaldoni">Giacomo Gianfaldoni</name><affiliation wicri:level="1"><inist:fA14 i1="07"><s1>Department of Haematology, Azienda Ospedaliera Universitaria Careggi</s1><s2>Florence</s2><s3>ITA</s3><sZ>7 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>Florence</wicri:noRegion></affiliation></author><author><name sortKey="Socie, Gerard" sort="Socie, Gerard" uniqKey="Socie G" first="Gérard" last="Socie">Gérard Socie</name><affiliation wicri:level="3"><inist:fA14 i1="08"><s1>Service d'Hematologie, Hospital Saint Louis and INSERM</s1><s2>Paris</s2><s3>FRA</s3><sZ>8 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Browne, Paul" sort="Browne, Paul" uniqKey="Browne P" first="Paul" last="Browne">Paul Browne</name><affiliation wicri:level="1"><inist:fA14 i1="09"><s1>Department of Haematology, St James Hospital</s1><s2>Dublin</s2><s3>IRL</s3><sZ>9 aut.</sZ></inist:fA14><country>Irlande (pays)</country><wicri:noRegion>Dublin</wicri:noRegion></affiliation></author><author><name sortKey="Geller, Robert" sort="Geller, Robert" uniqKey="Geller R" first="Robert" last="Geller">Robert Geller</name><affiliation wicri:level="1"><inist:fA14 i1="10"><s1>Alexion Pharmaceuticals Inc</s1><s2>Cheshire, CT</s2><s3>USA</s3><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Alexion Pharmaceuticals Inc</wicri:noRegion></affiliation></author><author><name sortKey="Rother, Russell P" sort="Rother, Russell P" uniqKey="Rother R" first="Russell P." last="Rother">Russell P. Rother</name><affiliation wicri:level="1"><inist:fA14 i1="10"><s1>Alexion Pharmaceuticals Inc</s1><s2>Cheshire, CT</s2><s3>USA</s3><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Alexion Pharmaceuticals Inc</wicri:noRegion></affiliation></author><author><name sortKey="Muus, Petra" sort="Muus, Petra" uniqKey="Muus P" first="Petra" last="Muus">Petra Muus</name><affiliation wicri:level="3"><inist:fA14 i1="11"><s1>Department of Haematology, Radbound University</s1><s2>Nijmegen</s2><s3>NLD</s3><sZ>12 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Nimègue</settlement><region type="province" nuts="2">Gueldre</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">08-0363566</idno><date when="2008">2008</date><idno type="stanalyst">PASCAL 08-0363566 INIST</idno><idno type="RBID">Pascal:08-0363566</idno><idno type="wicri:Area/PascalFrancis/Corpus">003403</idno><idno type="wicri:Area/PascalFrancis/Curation">002C47</idno><idno type="wicri:Area/PascalFrancis/Checkpoint">003283</idno><idno type="wicri:explorRef" wicri:stream="PascalFrancis" wicri:step="Checkpoint">003283</idno><idno type="wicri:doubleKey">0007-1048:2008:Schubert J:eculizumab:a:terminal</idno><idno type="wicri:Area/Main/Merge">009697</idno><idno type="wicri:Area/Main/Curation">008D72</idno><idno type="wicri:Area/Main/Exploration">008D72</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Eculizumab, a terminal complement inhibitor, improves anaemia in patients with paroxysmal nocturnal haemoglobinuria</title><author><name sortKey="Schubert, Jorg" sort="Schubert, Jorg" uniqKey="Schubert J" first="Jörg" last="Schubert">Jörg Schubert</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Internal Medicine I, Saarland University Medical School</s1><s2>Homburg Saar</s2><s3>DEU</s3><sZ>1 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>Homburg Saar</wicri:noRegion><wicri:noRegion>Saarland University Medical School</wicri:noRegion><wicri:noRegion>Homburg Saar</wicri:noRegion></affiliation></author><author><name sortKey="Hillmen, Peter" sort="Hillmen, Peter" uniqKey="Hillmen P" first="Peter" last="Hillmen">Peter Hillmen</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Haematology, St James's Institute of Oncology</s1><s2>Leeds</s2><s3>GBR</s3><sZ>2 aut.</sZ></inist:fA14><country>Royaume-Uni</country><wicri:noRegion>Leeds</wicri:noRegion></affiliation></author><author><name sortKey="Roth, Alexander" sort="Roth, Alexander" uniqKey="Roth A" first="Alexander" last="Röth">Alexander Röth</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Department of Haematology, University Hospital Essen</s1><s3>DEU</s3><sZ>3 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>University Hospital Essen</wicri:noRegion><wicri:noRegion>Department of Haematology, University Hospital Essen</wicri:noRegion></affiliation></author><author><name sortKey="Young, Neal S" sort="Young, Neal S" uniqKey="Young N" first="Neal S." last="Young">Neal S. Young</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Cell Biology Section, Clinical Hematology Branch, NHLBI, NIH</s1><s2>Bethesda, MD</s2><s3>USA</s3><sZ>4 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Bethesda, MD</wicri:noRegion></affiliation></author><author><name sortKey="Elebute, Modupe O" sort="Elebute, Modupe O" uniqKey="Elebute M" first="Modupe O." last="Elebute">Modupe O. Elebute</name><affiliation wicri:level="3"><inist:fA14 i1="05"><s1>Department of Cellular and Molecular Medicine, St. Georges Hospital</s1><s2>London</s2><s3>GBR</s3><sZ>5 aut.</sZ></inist:fA14><country>Royaume-Uni</country><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Szer, Jeffrey" sort="Szer, Jeffrey" uniqKey="Szer J" first="Jeffrey" last="Szer">Jeffrey Szer</name><affiliation wicri:level="3"><inist:fA14 i1="06"><s1>Department of Clinical Haematology, Royal Melbourne Hospital</s1><s2>Melbourne</s2><s3>AUS</s3><sZ>6 aut.</sZ></inist:fA14><country>Australie</country><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Gianfaldoni, Giacomo" sort="Gianfaldoni, Giacomo" uniqKey="Gianfaldoni G" first="Giacomo" last="Gianfaldoni">Giacomo Gianfaldoni</name><affiliation wicri:level="1"><inist:fA14 i1="07"><s1>Department of Haematology, Azienda Ospedaliera Universitaria Careggi</s1><s2>Florence</s2><s3>ITA</s3><sZ>7 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>Florence</wicri:noRegion></affiliation></author><author><name sortKey="Socie, Gerard" sort="Socie, Gerard" uniqKey="Socie G" first="Gérard" last="Socie">Gérard Socie</name><affiliation wicri:level="3"><inist:fA14 i1="08"><s1>Service d'Hematologie, Hospital Saint Louis and INSERM</s1><s2>Paris</s2><s3>FRA</s3><sZ>8 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Browne, Paul" sort="Browne, Paul" uniqKey="Browne P" first="Paul" last="Browne">Paul Browne</name><affiliation wicri:level="1"><inist:fA14 i1="09"><s1>Department of Haematology, St James Hospital</s1><s2>Dublin</s2><s3>IRL</s3><sZ>9 aut.</sZ></inist:fA14><country>Irlande (pays)</country><wicri:noRegion>Dublin</wicri:noRegion></affiliation></author><author><name sortKey="Geller, Robert" sort="Geller, Robert" uniqKey="Geller R" first="Robert" last="Geller">Robert Geller</name><affiliation wicri:level="1"><inist:fA14 i1="10"><s1>Alexion Pharmaceuticals Inc</s1><s2>Cheshire, CT</s2><s3>USA</s3><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Alexion Pharmaceuticals Inc</wicri:noRegion></affiliation></author><author><name sortKey="Rother, Russell P" sort="Rother, Russell P" uniqKey="Rother R" first="Russell P." last="Rother">Russell P. Rother</name><affiliation wicri:level="1"><inist:fA14 i1="10"><s1>Alexion Pharmaceuticals Inc</s1><s2>Cheshire, CT</s2><s3>USA</s3><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Alexion Pharmaceuticals Inc</wicri:noRegion></affiliation></author><author><name sortKey="Muus, Petra" sort="Muus, Petra" uniqKey="Muus P" first="Petra" last="Muus">Petra Muus</name><affiliation wicri:level="3"><inist:fA14 i1="11"><s1>Department of Haematology, Radbound University</s1><s2>Nijmegen</s2><s3>NLD</s3><sZ>12 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Nimègue</settlement><region type="province" nuts="2">Gueldre</region></placeName></affiliation></author></analytic><series><title level="j" type="main">British journal of haematology</title><title level="j" type="abbreviated">Br. j. haematol.</title><idno type="ISSN">0007-1048</idno><imprint><date when="2008">2008</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">British journal of haematology</title><title level="j" type="abbreviated">Br. j. haematol.</title><idno type="ISSN">0007-1048</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Complement</term><term>Eculizumab</term><term>Hematology</term><term>Hemoglobin</term><term>Hemolysis</term><term>Human</term><term>Inhibitor</term><term>Nocturnal paroxystic anemia</term><term>Transfusion</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Eculizumab</term><term>Complément</term><term>Inhibiteur</term><term>Anémie hémolytique de Marchiafava-Micheli</term><term>Homme</term><term>Hémoglobine</term><term>Hémolyse</term><term>Transfusion</term><term>Hématologie</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Homme</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">In paroxysmal nocturnal haemoglobinuria (PNH), chronic destruction of PNH red blood cells (RBCs) by complement leads to anaemia and other serious morbidities. Eculizumab inhibits terminal complement-mediated PNH RBC destruction by targeting C5. In the phase III, double-blind, placebo-controlled, TRIUMPH study, eculizumab reduced haemolysis, stabilized haemoglobin levels, reduced transfusion requirements and improved fatigue in patients with PNH. Herein, we explored the effects of eculizumab on measures of anaemia in patients from the TRIUMPH study and the open-label SHEPHERD study, a more heterogeneous population. Eculizumab reduced haemolysis regardless of pretreatment transfusion requirements and regardless of whether or not patients became transfusion-dependent during treatment (P< 0.001). Reduction in haemolysis was associated with increased PNH RBC counts (P <0.001) while reticulocyte counts remained elevated. Eculizumab-treated patients demonstrated significantly higher levels of haemoglobin as compared with placebo in TRIUMPH and relative to baseline levels in SHEPHERD (P < 0.001 for each study). Eculizumab lowered transfusion requirement across multiple pretreatment transfusion strata and eliminated transfusion support in a majority of both TRIUMPH and SHEPHERD patients (P < 0-001). Patients who required some transfusion support during treatment with eculizumab showed a reduction in haemolysis and transfusion requirements and an improvement in fatigue. Eculizumab reduces haemolysis and improves anaemia and fatigue, regardless of transfusion requirements.</div></front></TEI><affiliations><list><country><li>Allemagne</li><li>Australie</li><li>France</li><li>Irlande (pays)</li><li>Italie</li><li>Pays-Bas</li><li>Royaume-Uni</li><li>États-Unis</li></country><region><li>Angleterre</li><li>Grand Londres</li><li>Gueldre</li><li>Victoria (État)</li><li>Île-de-France</li></region><settlement><li>Londres</li><li>Melbourne</li><li>Nimègue</li><li>Paris</li></settlement></list><tree><country name="Allemagne"><noRegion><name sortKey="Schubert, Jorg" sort="Schubert, Jorg" uniqKey="Schubert J" first="Jörg" last="Schubert">Jörg Schubert</name></noRegion><name sortKey="Roth, Alexander" sort="Roth, Alexander" uniqKey="Roth A" first="Alexander" last="Röth">Alexander Röth</name></country><country name="Royaume-Uni"><noRegion><name sortKey="Hillmen, Peter" sort="Hillmen, Peter" uniqKey="Hillmen P" first="Peter" last="Hillmen">Peter Hillmen</name></noRegion><name sortKey="Elebute, Modupe O" sort="Elebute, Modupe O" uniqKey="Elebute M" first="Modupe O." last="Elebute">Modupe O. Elebute</name></country><country name="États-Unis"><noRegion><name sortKey="Young, Neal S" sort="Young, Neal S" uniqKey="Young N" first="Neal S." last="Young">Neal S. Young</name></noRegion><name sortKey="Geller, Robert" sort="Geller, Robert" uniqKey="Geller R" first="Robert" last="Geller">Robert Geller</name><name sortKey="Rother, Russell P" sort="Rother, Russell P" uniqKey="Rother R" first="Russell P." last="Rother">Russell P. Rother</name></country><country name="Australie"><region name="Victoria (État)"><name sortKey="Szer, Jeffrey" sort="Szer, Jeffrey" uniqKey="Szer J" first="Jeffrey" last="Szer">Jeffrey Szer</name></region></country><country name="Italie"><noRegion><name sortKey="Gianfaldoni, Giacomo" sort="Gianfaldoni, Giacomo" uniqKey="Gianfaldoni G" first="Giacomo" last="Gianfaldoni">Giacomo Gianfaldoni</name></noRegion></country><country name="France"><region name="Île-de-France"><name sortKey="Socie, Gerard" sort="Socie, Gerard" uniqKey="Socie G" first="Gérard" last="Socie">Gérard Socie</name></region></country><country name="Irlande (pays)"><noRegion><name sortKey="Browne, Paul" sort="Browne, Paul" uniqKey="Browne P" first="Paul" last="Browne">Paul Browne</name></noRegion></country><country name="Pays-Bas"><region name="Gueldre"><name sortKey="Muus, Petra" sort="Muus, Petra" uniqKey="Muus P" first="Petra" last="Muus">Petra Muus</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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