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Prediction of treatment response to adalimumab: a double-blind placebo-controlled study of circulating microRNA in patients with early rheumatoid arthritis.

Identifieur interne : 000023 ( Main/Exploration ); précédent : 000022; suivant : 000024

Prediction of treatment response to adalimumab: a double-blind placebo-controlled study of circulating microRNA in patients with early rheumatoid arthritis.

Auteurs : S B Krintel [Danemark] ; C. Dehlendorff [Danemark] ; M L Hetland [Danemark] ; K. H Rslev-Petersen [Danemark] ; K K Andersen [Danemark] ; P. Junker [Danemark] ; J. P Denphant [Danemark] ; T. Ellingsen [Danemark] ; P. Ahlquist [Danemark] ; H M Lindegaard [Danemark] ; A. Linauskas [Danemark] ; A. Schlemmer [Danemark] ; M Y Dam [Danemark] ; I. Hansen [Danemark] ; H C Horn [Danemark] ; A. J Rgensen [Danemark] ; J. Raun [Danemark] ; C G Ammitzb Ll [Danemark] ; M. Stergaard [Danemark] ; K. Stengaard-Pedersen [Danemark] ; J S Johansen [Danemark]

Source :

RBID : pubmed:25939484

Abstract

At least 30% of patients with rheumatoid arthritis (RA) do not respond to biologic agents, which emphasizes the need of predictive biomarkers. We aimed to identify microRNAs (miRNAs) predictive of response to adalimumab in 180 treatment-naïve RA patients enrolled in the OPtimized treatment algorithm for patients with early RA (OPERA) Study, an investigator-initiated, prospective, double-blind placebo-controlled study. Patients were randomized to adalimumab 40 mg (n=89) or placebo-adalimumab (n=91) subcutaneously in combination with methotrexate. Expressions of 377 miRNAs were determined using TaqMan Human MicroRNA LDA, A Card v2.0 (Applied Biosystems). Associations between miRNAs and treatment response were tested using interaction analyses. MiRNAs with a P-value <0.05 using three different normalizations were included in a multivariate model. After backwards elimination, the combination of low expression of miR-22 and high expression of miR-886.3p was associated with EULAR good response. Future studies to assess the utility of these miRNAs as predictive biomarkers are needed.

DOI: 10.1038/tpj.2015.30
PubMed: 25939484


Affiliations:


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Le document en format XML

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<name sortKey="Krintel, S B" sort="Krintel, S B" uniqKey="Krintel S" first="S B" last="Krintel">S B Krintel</name>
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<nlm:affiliation>Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Copenhagen University Hospital at Glostrup, Glostrup, Denmark.</nlm:affiliation>
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<name sortKey="Dehlendorff, C" sort="Dehlendorff, C" uniqKey="Dehlendorff C" first="C" last="Dehlendorff">C. Dehlendorff</name>
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<nlm:affiliation>Danish Cancer Society Research Center, Danish Cancer Society, Copenhagen, Denmark.</nlm:affiliation>
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<name sortKey="Hetland, M L" sort="Hetland, M L" uniqKey="Hetland M" first="M L" last="Hetland">M L Hetland</name>
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<nlm:affiliation>Department of Rheumatology, Odense University Hospital, Odense, Denmark.</nlm:affiliation>
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<name sortKey="Linauskas, A" sort="Linauskas, A" uniqKey="Linauskas A" first="A" last="Linauskas">A. Linauskas</name>
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<name sortKey="Schlemmer, A" sort="Schlemmer, A" uniqKey="Schlemmer A" first="A" last="Schlemmer">A. Schlemmer</name>
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<name sortKey="Dam, M Y" sort="Dam, M Y" uniqKey="Dam M" first="M Y" last="Dam">M Y Dam</name>
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<nlm:affiliation>Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark.</nlm:affiliation>
<country xml:lang="fr">Danemark</country>
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<name sortKey="Hansen, I" sort="Hansen, I" uniqKey="Hansen I" first="I" last="Hansen">I. Hansen</name>
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<nlm:affiliation>Department of Rheumatology, Viborg Hospital, Viborg, Denmark.</nlm:affiliation>
<country xml:lang="fr">Danemark</country>
<wicri:regionArea>Department of Rheumatology, Viborg Hospital, Viborg</wicri:regionArea>
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<name sortKey="Horn, H C" sort="Horn, H C" uniqKey="Horn H" first="H C" last="Horn">H C Horn</name>
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<nlm:affiliation>Department of Rheumatology, Vejle Hospital, Vejle, Denmark.</nlm:affiliation>
<country xml:lang="fr">Danemark</country>
<wicri:regionArea>Department of Rheumatology, Vejle Hospital, Vejle</wicri:regionArea>
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<name sortKey="J Rgensen, A" sort="J Rgensen, A" uniqKey="J Rgensen A" first="A" last="J Rgensen">A. J Rgensen</name>
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<nlm:affiliation>Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark.</nlm:affiliation>
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<name sortKey="Raun, J" sort="Raun, J" uniqKey="Raun J" first="J" last="Raun">J. Raun</name>
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</author>
<author>
<name sortKey="Ammitzb Ll, C G" sort="Ammitzb Ll, C G" uniqKey="Ammitzb Ll C" first="C G" last="Ammitzb Ll">C G Ammitzb Ll</name>
<affiliation wicri:level="1">
<nlm:affiliation>Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark.</nlm:affiliation>
<country xml:lang="fr">Danemark</country>
<wicri:regionArea>Department of Rheumatology, Aarhus University Hospital, Aarhus</wicri:regionArea>
<wicri:noRegion>Aarhus</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey=" Stergaard, M" sort=" Stergaard, M" uniqKey=" Stergaard M" first="M" last=" Stergaard">M. Stergaard</name>
<affiliation wicri:level="1">
<nlm:affiliation>Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Copenhagen University Hospital at Glostrup, Glostrup, Denmark.</nlm:affiliation>
<country xml:lang="fr">Danemark</country>
<wicri:regionArea>Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Copenhagen University Hospital at Glostrup, Glostrup</wicri:regionArea>
<wicri:noRegion>Glostrup</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Stengaard Pedersen, K" sort="Stengaard Pedersen, K" uniqKey="Stengaard Pedersen K" first="K" last="Stengaard-Pedersen">K. Stengaard-Pedersen</name>
<affiliation wicri:level="1">
<nlm:affiliation>Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark.</nlm:affiliation>
<country xml:lang="fr">Danemark</country>
<wicri:regionArea>Department of Rheumatology, Aarhus University Hospital, Aarhus</wicri:regionArea>
<wicri:noRegion>Aarhus</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Johansen, J S" sort="Johansen, J S" uniqKey="Johansen J" first="J S" last="Johansen">J S Johansen</name>
<affiliation wicri:level="3">
<nlm:affiliation>Department of Medicine, Copenhagen University Hospital at Herlev, Copenhagen, Denmark.</nlm:affiliation>
<country xml:lang="fr">Danemark</country>
<wicri:regionArea>Department of Medicine, Copenhagen University Hospital at Herlev, Copenhagen</wicri:regionArea>
<placeName>
<settlement type="city">Copenhague</settlement>
<region type="région" nuts="2">Hovedstaden</region>
</placeName>
</affiliation>
</author>
</analytic>
<series>
<title level="j">The pharmacogenomics journal</title>
<idno type="e-ISSN">1473-1150</idno>
<imprint>
<date when="2016" type="published">2016</date>
</imprint>
</series>
</biblStruct>
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<profileDesc>
<textClass></textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">At least 30% of patients with rheumatoid arthritis (RA) do not respond to biologic agents, which emphasizes the need of predictive biomarkers. We aimed to identify microRNAs (miRNAs) predictive of response to adalimumab in 180 treatment-naïve RA patients enrolled in the OPtimized treatment algorithm for patients with early RA (OPERA) Study, an investigator-initiated, prospective, double-blind placebo-controlled study. Patients were randomized to adalimumab 40 mg (n=89) or placebo-adalimumab (n=91) subcutaneously in combination with methotrexate. Expressions of 377 miRNAs were determined using TaqMan Human MicroRNA LDA, A Card v2.0 (Applied Biosystems). Associations between miRNAs and treatment response were tested using interaction analyses. MiRNAs with a P-value <0.05 using three different normalizations were included in a multivariate model. After backwards elimination, the combination of low expression of miR-22 and high expression of miR-886.3p was associated with EULAR good response. Future studies to assess the utility of these miRNAs as predictive biomarkers are needed.</div>
</front>
</TEI>
<affiliations>
<list>
<country>
<li>Danemark</li>
</country>
<region>
<li>Hovedstaden</li>
</region>
<settlement>
<li>Copenhague</li>
</settlement>
</list>
<tree>
<country name="Danemark">
<noRegion>
<name sortKey="Krintel, S B" sort="Krintel, S B" uniqKey="Krintel S" first="S B" last="Krintel">S B Krintel</name>
</noRegion>
<name sortKey=" Stergaard, M" sort=" Stergaard, M" uniqKey=" Stergaard M" first="M" last=" Stergaard">M. Stergaard</name>
<name sortKey="Ahlquist, P" sort="Ahlquist, P" uniqKey="Ahlquist P" first="P" last="Ahlquist">P. Ahlquist</name>
<name sortKey="Ammitzb Ll, C G" sort="Ammitzb Ll, C G" uniqKey="Ammitzb Ll C" first="C G" last="Ammitzb Ll">C G Ammitzb Ll</name>
<name sortKey="Andersen, K K" sort="Andersen, K K" uniqKey="Andersen K" first="K K" last="Andersen">K K Andersen</name>
<name sortKey="Dam, M Y" sort="Dam, M Y" uniqKey="Dam M" first="M Y" last="Dam">M Y Dam</name>
<name sortKey="Dehlendorff, C" sort="Dehlendorff, C" uniqKey="Dehlendorff C" first="C" last="Dehlendorff">C. Dehlendorff</name>
<name sortKey="Ellingsen, T" sort="Ellingsen, T" uniqKey="Ellingsen T" first="T" last="Ellingsen">T. Ellingsen</name>
<name sortKey="H Rslev Petersen, K" sort="H Rslev Petersen, K" uniqKey="H Rslev Petersen K" first="K" last="H Rslev-Petersen">K. H Rslev-Petersen</name>
<name sortKey="Hansen, I" sort="Hansen, I" uniqKey="Hansen I" first="I" last="Hansen">I. Hansen</name>
<name sortKey="Hetland, M L" sort="Hetland, M L" uniqKey="Hetland M" first="M L" last="Hetland">M L Hetland</name>
<name sortKey="Horn, H C" sort="Horn, H C" uniqKey="Horn H" first="H C" last="Horn">H C Horn</name>
<name sortKey="J Rgensen, A" sort="J Rgensen, A" uniqKey="J Rgensen A" first="A" last="J Rgensen">A. J Rgensen</name>
<name sortKey="Johansen, J S" sort="Johansen, J S" uniqKey="Johansen J" first="J S" last="Johansen">J S Johansen</name>
<name sortKey="Junker, P" sort="Junker, P" uniqKey="Junker P" first="P" last="Junker">P. Junker</name>
<name sortKey="Linauskas, A" sort="Linauskas, A" uniqKey="Linauskas A" first="A" last="Linauskas">A. Linauskas</name>
<name sortKey="Lindegaard, H M" sort="Lindegaard, H M" uniqKey="Lindegaard H" first="H M" last="Lindegaard">H M Lindegaard</name>
<name sortKey="P Denphant, J" sort="P Denphant, J" uniqKey="P Denphant J" first="J" last="P Denphant">J. P Denphant</name>
<name sortKey="Raun, J" sort="Raun, J" uniqKey="Raun J" first="J" last="Raun">J. Raun</name>
<name sortKey="Schlemmer, A" sort="Schlemmer, A" uniqKey="Schlemmer A" first="A" last="Schlemmer">A. Schlemmer</name>
<name sortKey="Stengaard Pedersen, K" sort="Stengaard Pedersen, K" uniqKey="Stengaard Pedersen K" first="K" last="Stengaard-Pedersen">K. Stengaard-Pedersen</name>
</country>
</tree>
</affiliations>
</record>

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