Systematic review and mixed treatment comparison meta-analysis of randomized clinical trials of primary oral antifungal prophylaxis in allogeneic hematopoietic cell transplant recipients
Identifieur interne : 002782 ( Main/Exploration ); précédent : 002781; suivant : 002783Systematic review and mixed treatment comparison meta-analysis of randomized clinical trials of primary oral antifungal prophylaxis in allogeneic hematopoietic cell transplant recipients
Auteurs : Eric J. Bow ; David J. Vanness ; Monica Slavin [Australie] ; Catherine Cordonnier [France] ; Oliver A. Cornely [Allemagne] ; David I. Marks [Royaume-Uni] ; Antonio Pagliuca [Royaume-Uni] ; Carlos Solano [Espagne] ; Lael Cragin ; Alissa J. Shaul ; Sonja Sorensen ; Richard Chambers ; Michal Kantecki [France] ; David Weinstein [France] ; Haran Schlamm [États-Unis]Source :
- BMC Infectious Diseases [ 1471-2334 ] ; 2015.
Descripteurs français
- KwdFr :
- MESH :
- traitement médicamenteux : Mycoses.
- usage thérapeutique : Antifongiques.
- Essais contrôlés randomisés comme sujet, Humains, Mycoses, Receveurs de transplantation, Théorème de Bayes, Transplantation de cellules souches hématopoïétiques.
English descriptors
- KwdEn :
- MESH :
- chemical , therapeutic use : Antifungal Agents.
- drug therapy : Mycoses.
- prevention & control : Mycoses.
- Bayes Theorem, Hematopoietic Stem Cell Transplantation, Humans, Randomized Controlled Trials as Topic, Transplant Recipients.
Abstract
Antifungal prophylaxis is a promising strategy for reducing invasive fungal infections (IFIs) in allogeneic hematopoietic cell transplant (alloHCT) recipients, but the optimum prophylactic agent is unknown. We used mixed treatment comparison (MTC) meta-analysis to compare clinical trials examining the use of oral antifungals for prophylaxis in alloHCT recipients, with the goal of informing medical decision-making.
Randomized controlled trials (RCTs) of fluconazole, itraconazole, posaconazole, and voriconazole for primary antifungal prophylaxis were identified through a systematic literature review. Outcomes of interest (incidence of IFI/invasive aspergillosis/invasive candidiasis, all-cause mortality, and use of other antifungals) were extracted from eligible RCTs and incorporated into a Bayesian hierarchical random-effects MTC.
Five eligible RCTs, randomizing 2147 patients in total, were included. Relative to fluconazole, prophylaxis with itraconazole (odds ratio [OR]: 0.52; interquartile range [IQR]: 0.35–0.76), posaconazole (OR: 0.56; IQR: 0.32–0.99), and voriconazole (OR: 0.46; IQR: 0.28–0.73) reduced incidence of overall proven/probable IFI. Posaconazole (OR: 0.31; IQR: 0.17–0.58) and voriconazole (OR: 0.33; IQR: 0.17–0.58) prophylaxis reduced proven/probable invasive aspergillosis more than itraconazole (OR: 0.68; IQR: 0.42–1.12). All-cause mortality was similar across all mould-active agents.
As expected, mould-active azoles prevented IFIs, particularly invasive aspergillosis, more effectively than fluconazole in alloHCT recipients. The paucity of comparative efficacy data suggests that other factors such as long-term tolerability, availability of intravenous formulations, local IFI epidemiology, and drug costs may need to form the basis for selection among the mould-active azoles.
The online version of this article (doi:10.1186/s12879-015-0855-6) contains supplementary material, which is available to authorized users.
Url:
DOI: 10.1186/s12879-015-0855-6
PubMed: 25887385
PubMed Central: 4374298
Affiliations:
- Allemagne, Australie, Espagne, France, Royaume-Uni, États-Unis
- Angleterre, Grand Londres, Victoria (État), État de New York, Île-de-France
- Créteil, Londres, Melbourne, New York, Paris
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Le document en format XML
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Bow</name><affiliation><nlm:aff id="Aff1">CancerCare Manitoba, 675 McDermot Ave, Winnipeg, MB Canada</nlm:aff><wicri:noCountry code="subfield">MB Canada</wicri:noCountry></affiliation></author><author><name sortKey="Vanness, David J" sort="Vanness, David J" uniqKey="Vanness D" first="David J" last="Vanness">David J. Vanness</name><affiliation><nlm:aff id="Aff2">University of Wisconsin and Visiting Scientist at Evidera, Madison, Wisconsin USA</nlm:aff><wicri:noCountry code="subfield">Wisconsin USA</wicri:noCountry></affiliation></author><author><name sortKey="Slavin, Monica" sort="Slavin, Monica" uniqKey="Slavin M" first="Monica" last="Slavin">Monica Slavin</name><affiliation wicri:level="3"><nlm:aff id="Aff3">Royal Melbourne Hospital, Melbourne, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Royal Melbourne Hospital, Melbourne</wicri:regionArea><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Cordonnier, Catherine" sort="Cordonnier, Catherine" uniqKey="Cordonnier C" first="Catherine" last="Cordonnier">Catherine Cordonnier</name><affiliation wicri:level="3"><nlm:aff id="Aff4">Assistance Publique-Hopitaux de Paris, Hôpital Henri Mondor and Université Paris-Est-Créteil, Creteil, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Assistance Publique-Hopitaux de Paris, Hôpital Henri Mondor and Université Paris-Est-Créteil, Creteil</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Créteil</settlement></placeName></affiliation></author><author><name sortKey="Cornely, Oliver A" sort="Cornely, Oliver A" uniqKey="Cornely O" first="Oliver A" last="Cornely">Oliver A. Cornely</name><affiliation wicri:level="1"><nlm:aff id="Aff5">Department I of Internal Medicine, Clinical Trials Centre Cologne, ZKS Köln, BMBF 01KN1106, Center for Integrated Oncology CIO KölnBonn, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department I of Internal Medicine, Clinical Trials Centre Cologne, ZKS Köln, BMBF 01KN1106, Center for Integrated Oncology CIO KölnBonn, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne</wicri:regionArea><wicri:noRegion>Cologne</wicri:noRegion><wicri:noRegion>Cologne</wicri:noRegion><wicri:noRegion>Cologne</wicri:noRegion></affiliation></author><author><name sortKey="Marks, David I" sort="Marks, David I" uniqKey="Marks D" first="David I" last="Marks">David I. Marks</name><affiliation wicri:level="1"><nlm:aff id="Aff6">University Hospitals Bristol NHS Foundation Trust, Bristol, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>University Hospitals Bristol NHS Foundation Trust, Bristol</wicri:regionArea><wicri:noRegion>Bristol</wicri:noRegion></affiliation></author><author><name sortKey="Pagliuca, Antonio" sort="Pagliuca, Antonio" uniqKey="Pagliuca A" first="Antonio" last="Pagliuca">Antonio Pagliuca</name><affiliation wicri:level="3"><nlm:aff id="Aff7">King’s College Hospital, London, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>King’s College Hospital, London</wicri:regionArea><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="Solano, Carlos" sort="Solano, Carlos" uniqKey="Solano C" first="Carlos" last="Solano">Carlos Solano</name><affiliation wicri:level="1"><nlm:aff id="Aff8">Hospital Clínico, INCLIVA Foundation, University of Valencia, Valencia, Spain</nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>Hospital Clínico, INCLIVA Foundation, University of Valencia, Valencia</wicri:regionArea><wicri:noRegion>Valencia</wicri:noRegion></affiliation></author><author><name sortKey="Cragin, Lael" sort="Cragin, Lael" uniqKey="Cragin L" first="Lael" last="Cragin">Lael Cragin</name><affiliation><nlm:aff id="Aff9">Evidera, Bethesda, Maryland USA</nlm:aff><wicri:noCountry code="subfield">Maryland USA</wicri:noCountry></affiliation></author><author><name sortKey="Shaul, Alissa J" sort="Shaul, Alissa J" uniqKey="Shaul A" first="Alissa J" last="Shaul">Alissa J. Shaul</name><affiliation><nlm:aff id="Aff9">Evidera, Bethesda, Maryland USA</nlm:aff><wicri:noCountry code="subfield">Maryland USA</wicri:noCountry></affiliation></author><author><name sortKey="Sorensen, Sonja" sort="Sorensen, Sonja" uniqKey="Sorensen S" first="Sonja" last="Sorensen">Sonja Sorensen</name><affiliation><nlm:aff id="Aff9">Evidera, Bethesda, Maryland USA</nlm:aff><wicri:noCountry code="subfield">Maryland USA</wicri:noCountry></affiliation></author><author><name sortKey="Chambers, Richard" sort="Chambers, Richard" uniqKey="Chambers R" first="Richard" last="Chambers">Richard Chambers</name><affiliation><nlm:aff id="Aff10">Pfizer, Collegeville, Pennsylvania USA</nlm:aff><wicri:noCountry code="subfield">Pennsylvania USA</wicri:noCountry></affiliation></author><author><name sortKey="Kantecki, Michal" sort="Kantecki, Michal" uniqKey="Kantecki M" first="Michal" last="Kantecki">Michal Kantecki</name><affiliation wicri:level="3"><nlm:aff id="Aff11">Pfizer, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Pfizer, Paris</wicri:regionArea><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="Weinstein, David" sort="Weinstein, David" uniqKey="Weinstein D" first="David" last="Weinstein">David Weinstein</name><affiliation wicri:level="3"><nlm:aff id="Aff11">Pfizer, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Pfizer, Paris</wicri:regionArea><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="Schlamm, Haran" sort="Schlamm, Haran" uniqKey="Schlamm H" first="Haran" last="Schlamm">Haran Schlamm</name><affiliation wicri:level="3"><nlm:aff id="Aff12">HTS Pharma Consulting, New York, New York USA</nlm:aff><country>États-Unis</country><placeName><settlement type="city">New York</settlement><region type="state">État de New York</region></placeName><wicri:orgArea>HTS Pharma Consulting, New York</wicri:orgArea></affiliation></author></analytic><series><title level="j">BMC Infectious Diseases</title><idno type="eISSN">1471-2334</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antifungal Agents (therapeutic use)</term><term>Bayes Theorem</term><term>Hematopoietic Stem Cell Transplantation</term><term>Humans</term><term>Mycoses (drug therapy)</term><term>Mycoses (prevention & control)</term><term>Randomized Controlled Trials as Topic</term><term>Transplant Recipients</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Antifongiques (usage thérapeutique)</term><term>Essais contrôlés randomisés comme sujet</term><term>Humains</term><term>Mycoses ()</term><term>Mycoses (traitement médicamenteux)</term><term>Receveurs de transplantation</term><term>Théorème de Bayes</term><term>Transplantation de cellules souches hématopoïétiques</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Antifungal Agents</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Mycoses</term></keywords><keywords scheme="MESH" qualifier="prevention & control" xml:lang="en"><term>Mycoses</term></keywords><keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Mycoses</term></keywords><keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>Antifongiques</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Bayes Theorem</term><term>Hematopoietic Stem Cell Transplantation</term><term>Humans</term><term>Randomized Controlled Trials as Topic</term><term>Transplant Recipients</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Essais contrôlés randomisés comme sujet</term><term>Humains</term><term>Mycoses</term><term>Receveurs de transplantation</term><term>Théorème de Bayes</term><term>Transplantation de cellules souches hématopoïétiques</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>Antifungal prophylaxis is a promising strategy for reducing invasive fungal infections (IFIs) in allogeneic hematopoietic cell transplant (alloHCT) recipients, but the optimum prophylactic agent is unknown. We used mixed treatment comparison (MTC) meta-analysis to compare clinical trials examining the use of oral antifungals for prophylaxis in alloHCT recipients, with the goal of informing medical decision-making.</p></sec><sec><title>Methods</title><p>Randomized controlled trials (RCTs) of fluconazole, itraconazole, posaconazole, and voriconazole for primary antifungal prophylaxis were identified through a systematic literature review. Outcomes of interest (incidence of IFI/invasive aspergillosis/invasive candidiasis, all-cause mortality, and use of other antifungals) were extracted from eligible RCTs and incorporated into a Bayesian hierarchical random-effects MTC.</p></sec><sec><title>Results</title><p>Five eligible RCTs, randomizing 2147 patients in total, were included. Relative to fluconazole, prophylaxis with itraconazole (odds ratio [OR]: 0.52; interquartile range [IQR]: 0.35–0.76), posaconazole (OR: 0.56; IQR: 0.32–0.99), and voriconazole (OR: 0.46; IQR: 0.28–0.73) reduced incidence of overall proven/probable IFI. Posaconazole (OR: 0.31; IQR: 0.17–0.58) and voriconazole (OR: 0.33; IQR: 0.17–0.58) prophylaxis reduced proven/probable invasive aspergillosis more than itraconazole (OR: 0.68; IQR: 0.42–1.12). All-cause mortality was similar across all mould-active agents.</p></sec><sec><title>Conclusion</title><p>As expected, mould-active azoles prevented IFIs, particularly invasive aspergillosis, more effectively than fluconazole in alloHCT recipients. The paucity of comparative efficacy data suggests that other factors such as long-term tolerability, availability of intravenous formulations, local IFI epidemiology, and drug costs may need to form the basis for selection among the mould-active azoles.</p></sec><sec><title>Electronic supplementary material</title><p>The online version of this article (doi:10.1186/s12879-015-0855-6) contains supplementary material, which is available to authorized users.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Kontoyiannis, Dp" uniqKey="Kontoyiannis D">DP Kontoyiannis</name></author><author><name sortKey="Marr, Ka" uniqKey="Marr K">KA Marr</name></author><author><name sortKey="Park, Bj" uniqKey="Park B">BJ Park</name></author><author><name sortKey="Alexander, Bd" uniqKey="Alexander B">BD Alexander</name></author><author><name sortKey="Anaissie, Ej" uniqKey="Anaissie E">EJ Anaissie</name></author><author><name sortKey="Walsh, Tj" 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sortKey="Sobel, J" uniqKey="Sobel J">J Sobel</name></author><author><name sortKey="Viscoli, C" uniqKey="Viscoli C">C Viscoli</name></author></analytic></biblStruct><biblStruct></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Allemagne</li><li>Australie</li><li>Espagne</li><li>France</li><li>Royaume-Uni</li><li>États-Unis</li></country><region><li>Angleterre</li><li>Grand Londres</li><li>Victoria (État)</li><li>État de New York</li><li>Île-de-France</li></region><settlement><li>Créteil</li><li>Londres</li><li>Melbourne</li><li>New York</li><li>Paris</li></settlement></list><tree><noCountry><name sortKey="Bow, Eric J" sort="Bow, Eric J" uniqKey="Bow E" first="Eric J" last="Bow">Eric J. Bow</name><name sortKey="Chambers, Richard" sort="Chambers, Richard" uniqKey="Chambers R" first="Richard" last="Chambers">Richard Chambers</name><name sortKey="Cragin, Lael" sort="Cragin, Lael" uniqKey="Cragin L" first="Lael" last="Cragin">Lael Cragin</name><name sortKey="Shaul, Alissa J" sort="Shaul, Alissa J" uniqKey="Shaul A" first="Alissa J" last="Shaul">Alissa J. Shaul</name><name sortKey="Sorensen, Sonja" sort="Sorensen, Sonja" uniqKey="Sorensen S" first="Sonja" last="Sorensen">Sonja Sorensen</name><name sortKey="Vanness, David J" sort="Vanness, David J" uniqKey="Vanness D" first="David J" last="Vanness">David J. Vanness</name></noCountry><country name="Australie"><region name="Victoria (État)"><name sortKey="Slavin, Monica" sort="Slavin, Monica" uniqKey="Slavin M" first="Monica" last="Slavin">Monica Slavin</name></region></country><country name="France"><region name="Île-de-France"><name sortKey="Cordonnier, Catherine" sort="Cordonnier, Catherine" uniqKey="Cordonnier C" first="Catherine" last="Cordonnier">Catherine Cordonnier</name></region><name sortKey="Kantecki, Michal" sort="Kantecki, Michal" uniqKey="Kantecki M" first="Michal" last="Kantecki">Michal Kantecki</name><name sortKey="Weinstein, David" sort="Weinstein, David" uniqKey="Weinstein D" first="David" last="Weinstein">David Weinstein</name></country><country name="Allemagne"><noRegion><name sortKey="Cornely, Oliver A" sort="Cornely, Oliver A" uniqKey="Cornely O" first="Oliver A" last="Cornely">Oliver A. Cornely</name></noRegion></country><country name="Royaume-Uni"><noRegion><name sortKey="Marks, David I" sort="Marks, David I" uniqKey="Marks D" first="David I" last="Marks">David I. Marks</name></noRegion><name sortKey="Pagliuca, Antonio" sort="Pagliuca, Antonio" uniqKey="Pagliuca A" first="Antonio" last="Pagliuca">Antonio Pagliuca</name></country><country name="Espagne"><noRegion><name sortKey="Solano, Carlos" sort="Solano, Carlos" uniqKey="Solano C" first="Carlos" last="Solano">Carlos Solano</name></noRegion></country><country name="États-Unis"><region name="État de New York"><name sortKey="Schlamm, Haran" sort="Schlamm, Haran" uniqKey="Schlamm H" first="Haran" last="Schlamm">Haran Schlamm</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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