A single nucleotide polymorphism of IL6-receptor is associated with response to tocilizumab in rheumatoid arthritis patients.
Identifieur interne : 000126 ( France/Analysis ); précédent : 000125; suivant : 000127A single nucleotide polymorphism of IL6-receptor is associated with response to tocilizumab in rheumatoid arthritis patients.
Auteurs : Cécile Luxembourger [France] ; Adeline Ruyssen-Witrand [France] ; Chayma Ladhari [France] ; Cécile Rittore [France] ; Yannick Degboe [France] ; Jean-Francis Maillefert [France] ; Philippe Gaudin [France] ; Hubert Marotte [France] ; Daniel Wendling [France] ; Christian Jorgensen [France] ; Alain Cantagrel [France] ; Arnaud Constantin [France] ; Delphine Nigon [France] ; Isabelle Touitou [France] ; Jacques-Eric Gottenberg [France] ; Yves-Marie Pers [France]Source :
- The pharmacogenomics journal [ 1473-1150 ] ; 2019.
Descripteurs français
- KwdFr :
- Adulte d'âge moyen, Allèles, Anticorps monoclonaux humanisés (usage thérapeutique), Antirhumatismaux (usage thérapeutique), Femelle, Génotype, Humains, Interleukine-6 (génétique), Mâle, Polyarthrite rhumatoïde (génétique), Polyarthrite rhumatoïde (traitement médicamenteux), Polymorphisme de nucléotide simple (génétique), Récepteurs à l'interleukine-6 (génétique).
- MESH :
- génétique : Interleukine-6, Polyarthrite rhumatoïde, Polymorphisme de nucléotide simple, Récepteurs à l'interleukine-6.
- traitement médicamenteux : Polyarthrite rhumatoïde.
- usage thérapeutique : Anticorps monoclonaux humanisés, Antirhumatismaux.
- Adulte d'âge moyen, Allèles, Femelle, Génotype, Humains, Mâle.
English descriptors
- KwdEn :
- Alleles, Antibodies, Monoclonal, Humanized (therapeutic use), Antirheumatic Agents (therapeutic use), Arthritis, Rheumatoid (drug therapy), Arthritis, Rheumatoid (genetics), Female, Genotype, Humans, Interleukin-6 (genetics), Male, Middle Aged, Polymorphism, Single Nucleotide (genetics), Receptors, Interleukin-6 (genetics).
- MESH :
- chemical , genetics : Interleukin-6, Receptors, Interleukin-6.
- chemical , therapeutic use : Antibodies, Monoclonal, Humanized, Antirheumatic Agents.
- drug therapy : Arthritis, Rheumatoid.
- genetics : Arthritis, Rheumatoid, Polymorphism, Single Nucleotide.
- Alleles, Female, Genotype, Humans, Male, Middle Aged.
Abstract
Biological disease-modifying anti-rheumatic drugs (bDMARDs) have changed care of patients with rheumatoid arthritis (RA). However, bDMARDs are costly, can lead to serious infections, and induce a sustained remission in only 30% of RA patients. In this study, we sought to determine if the clinical response to treatment with Tocilizumab (TCZ), an IL-6 inhibitor, varied with genetic background. The efficacy of TCZ was assessed using the European League Against Rheumatism (EULAR) response criteria, measured after 3 months of treatment in two samples of French RA patients (TOCI and ROC studies). Single nucleotide polymorphisms (SNPs) in 21 candidate genes were genotyped using KasPar method (LGC-genomics, UK) and then analyzed to determine their contribution to variation in the response to treatment. One hundred twenty-three patients in the TOCI group (79.8%) and 48 patients in the ROC group (80%) experienced good or moderate EULAR response. The clinical response to treatment was associated with SNP genotype in the gene IL6R, with patients with the homozygous AA-genotype for rs12083537 (IL6R) showing a significantly better response than homozygous or heterozygous patients with the G allele [TOCI: 87.5% of responders for AA genotype vs. 72.2% for AG or GG genotype (p = 0.018); ROC patients: 89.2% of responders for AA genotype vs. 65.2% for AG or GG genotype, p = 0.044]. A meta-analysis combining data from the two cohorts confirmed the lower response rate in patients carrying a copy of the G allele (OR (95% CI) = 0.35 (0.16-0.61), p = 0.001). No association was found with any of the other SNPs tested.
DOI: 10.1038/s41397-019-0072-6
PubMed: 30647443
Affiliations:
- France
- Alsace (région administrative), Auvergne-Rhône-Alpes, Bourgogne, Bourgogne-Franche-Comté, Franche-Comté, Grand Est, Languedoc-Roussillon, Midi-Pyrénées, Occitanie (région administrative), Rhône-Alpes
- Besançon, Dijon, Grenoble, Montpellier, Strasbourg, Toulouse
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pubmed:30647443Le document en format XML
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wicri:level="3"><nlm:affiliation>Rhumatologie et Immunologie Clinique, CHU Purpan, Toulouse, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Rhumatologie et Immunologie Clinique, CHU Purpan, Toulouse</wicri:regionArea><placeName><region type="region">Occitanie (région administrative)</region><region type="old region">Midi-Pyrénées</region><settlement type="city">Toulouse</settlement></placeName></affiliation></author><author><name sortKey="Constantin, Arnaud" sort="Constantin, Arnaud" uniqKey="Constantin A" first="Arnaud" last="Constantin">Arnaud Constantin</name><affiliation wicri:level="3"><nlm:affiliation>Rhumatologie et Immunologie Clinique, CHU Purpan, Toulouse, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Rhumatologie et Immunologie Clinique, CHU Purpan, Toulouse</wicri:regionArea><placeName><region type="region">Occitanie (région administrative)</region><region type="old region">Midi-Pyrénées</region><settlement type="city">Toulouse</settlement></placeName></affiliation></author><author><name sortKey="Nigon, Delphine" sort="Nigon, Delphine" uniqKey="Nigon D" first="Delphine" last="Nigon">Delphine Nigon</name><affiliation wicri:level="3"><nlm:affiliation>Rhumatologie et Immunologie Clinique, CHU Purpan, Toulouse, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Rhumatologie et Immunologie Clinique, CHU Purpan, Toulouse</wicri:regionArea><placeName><region type="region">Occitanie (région administrative)</region><region type="old region">Midi-Pyrénées</region><settlement type="city">Toulouse</settlement></placeName></affiliation></author><author><name sortKey="Touitou, Isabelle" sort="Touitou, Isabelle" uniqKey="Touitou I" first="Isabelle" last="Touitou">Isabelle Touitou</name><affiliation wicri:level="3"><nlm:affiliation>Laboratoire de génétique des maladies rares et auto-inflammatoires (Centre de référence), Université Montpellier, CHU Montpellier, Montpellier, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire de génétique des maladies rares et auto-inflammatoires (Centre de référence), Université Montpellier, CHU Montpellier, Montpellier</wicri:regionArea><placeName><region type="region">Occitanie (région administrative)</region><region type="old region">Languedoc-Roussillon</region><settlement type="city">Montpellier</settlement></placeName></affiliation></author><author><name sortKey="Gottenberg, Jacques Eric" sort="Gottenberg, Jacques Eric" uniqKey="Gottenberg J" first="Jacques-Eric" last="Gottenberg">Jacques-Eric Gottenberg</name><affiliation wicri:level="3"><nlm:affiliation>Service de rhumatologie, Hôpital Hautepierre, CHU Strasbourg, Strasbourg, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Service de rhumatologie, Hôpital Hautepierre, CHU Strasbourg, Strasbourg</wicri:regionArea><placeName><region type="region">Grand Est</region><region type="old region">Alsace (région administrative)</region><settlement type="city">Strasbourg</settlement></placeName></affiliation></author><author><name sortKey="Pers, Yves Marie" sort="Pers, Yves Marie" uniqKey="Pers Y" first="Yves-Marie" last="Pers">Yves-Marie Pers</name><affiliation wicri:level="3"><nlm:affiliation>Clinical Immunology and Osteoarticular Diseases Therapeutic Unit, Lapeyronie University Hospital, Montpellier, France. ympers2000@yahoo.fr.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Clinical Immunology and Osteoarticular Diseases Therapeutic Unit, Lapeyronie University Hospital, Montpellier</wicri:regionArea><placeName><region type="region">Occitanie (région administrative)</region><region type="old region">Languedoc-Roussillon</region><settlement type="city">Montpellier</settlement></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2019">2019</date><idno type="RBID">pubmed:30647443</idno><idno type="pmid">30647443</idno><idno type="doi">10.1038/s41397-019-0072-6</idno><idno type="wicri:Area/PubMed/Corpus">000532</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000532</idno><idno type="wicri:Area/PubMed/Curation">000532</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000532</idno><idno type="wicri:Area/PubMed/Checkpoint">000584</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000584</idno><idno type="wicri:Area/Ncbi/Merge">001D64</idno><idno type="wicri:Area/Ncbi/Curation">001D64</idno><idno type="wicri:Area/Ncbi/Checkpoint">001D64</idno><idno type="wicri:Area/Main/Merge">001011</idno><idno type="wicri:Area/Main/Curation">001011</idno><idno type="wicri:Area/Main/Exploration">001011</idno><idno type="wicri:Area/France/Extraction">000126</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">A single nucleotide polymorphism of IL6-receptor is associated with response to tocilizumab in rheumatoid arthritis patients.</title><author><name sortKey="Luxembourger, Cecile" sort="Luxembourger, Cecile" uniqKey="Luxembourger C" first="Cécile" last="Luxembourger">Cécile Luxembourger</name><affiliation wicri:level="3"><nlm:affiliation>Rhumatologie et Immunologie Clinique, CHU Purpan, Toulouse, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Rhumatologie et Immunologie Clinique, CHU Purpan, Toulouse</wicri:regionArea><placeName><region type="region">Occitanie (région administrative)</region><region type="old region">Midi-Pyrénées</region><settlement type="city">Toulouse</settlement></placeName></affiliation></author><author><name sortKey="Ruyssen Witrand, Adeline" sort="Ruyssen Witrand, Adeline" uniqKey="Ruyssen Witrand A" first="Adeline" last="Ruyssen-Witrand">Adeline Ruyssen-Witrand</name><affiliation wicri:level="3"><nlm:affiliation>Rhumatologie et Immunologie Clinique, CHU Purpan, Toulouse, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Rhumatologie et Immunologie Clinique, CHU Purpan, Toulouse</wicri:regionArea><placeName><region type="region">Occitanie (région administrative)</region><region type="old region">Midi-Pyrénées</region><settlement type="city">Toulouse</settlement></placeName></affiliation></author><author><name sortKey="Ladhari, Chayma" sort="Ladhari, Chayma" uniqKey="Ladhari C" first="Chayma" last="Ladhari">Chayma Ladhari</name><affiliation wicri:level="3"><nlm:affiliation>Clinical Immunology and Osteoarticular Diseases Therapeutic Unit, Lapeyronie University Hospital, Montpellier, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Clinical Immunology and Osteoarticular Diseases Therapeutic Unit, Lapeyronie University Hospital, Montpellier</wicri:regionArea><placeName><region type="region">Occitanie (région administrative)</region><region type="old region">Languedoc-Roussillon</region><settlement type="city">Montpellier</settlement></placeName></affiliation></author><author><name sortKey="Rittore, Cecile" sort="Rittore, Cecile" uniqKey="Rittore C" first="Cécile" last="Rittore">Cécile Rittore</name><affiliation wicri:level="3"><nlm:affiliation>Laboratoire de génétique des maladies rares et auto-inflammatoires (Centre de référence), Université Montpellier, CHU Montpellier, Montpellier, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire de génétique des maladies rares et auto-inflammatoires (Centre de référence), Université Montpellier, CHU Montpellier, Montpellier</wicri:regionArea><placeName><region type="region">Occitanie (région administrative)</region><region type="old region">Languedoc-Roussillon</region><settlement type="city">Montpellier</settlement></placeName></affiliation></author><author><name sortKey="Degboe, Yannick" sort="Degboe, Yannick" uniqKey="Degboe Y" first="Yannick" last="Degboe">Yannick Degboe</name><affiliation wicri:level="3"><nlm:affiliation>Rhumatologie et Immunologie Clinique, CHU Purpan, Toulouse, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Rhumatologie et Immunologie Clinique, CHU Purpan, Toulouse</wicri:regionArea><placeName><region type="region">Occitanie (région administrative)</region><region type="old region">Midi-Pyrénées</region><settlement type="city">Toulouse</settlement></placeName></affiliation></author><author><name sortKey="Maillefert, Jean Francis" sort="Maillefert, Jean Francis" uniqKey="Maillefert J" first="Jean-Francis" last="Maillefert">Jean-Francis Maillefert</name><affiliation wicri:level="3"><nlm:affiliation>Service de Rhumatologie, Hôpital Bocage, CHU Dijon, Dijon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Service de Rhumatologie, Hôpital Bocage, CHU Dijon, Dijon</wicri:regionArea><placeName><region type="region">Bourgogne-Franche-Comté</region><region type="old region">Bourgogne</region><settlement type="city">Dijon</settlement></placeName></affiliation></author><author><name sortKey="Gaudin, Philippe" sort="Gaudin, Philippe" uniqKey="Gaudin P" first="Philippe" last="Gaudin">Philippe Gaudin</name><affiliation wicri:level="3"><nlm:affiliation>Service de Rhumatologie, Hôpital Sud, CHU Grenoble, Grenoble, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Service de Rhumatologie, Hôpital Sud, CHU Grenoble, Grenoble</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Grenoble</settlement></placeName></affiliation></author><author><name sortKey="Marotte, Hubert" sort="Marotte, Hubert" uniqKey="Marotte H" first="Hubert" last="Marotte">Hubert Marotte</name><affiliation wicri:level="1"><nlm:affiliation>Rhumatologie, CHU Saint Etienne, Saint-Priest-en-Jarez, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Rhumatologie, CHU Saint Etienne, Saint-Priest-en-Jarez</wicri:regionArea><wicri:noRegion>Saint-Priest-en-Jarez</wicri:noRegion><wicri:noRegion>Saint-Priest-en-Jarez</wicri:noRegion></affiliation></author><author><name sortKey="Wendling, Daniel" sort="Wendling, Daniel" uniqKey="Wendling D" first="Daniel" last="Wendling">Daniel Wendling</name><affiliation wicri:level="3"><nlm:affiliation>Rhumatologie, CHRU de Besançon, Besançon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Rhumatologie, CHRU de Besançon, Besançon</wicri:regionArea><placeName><region type="region">Bourgogne-Franche-Comté</region><region type="old region">Franche-Comté</region><settlement type="city">Besançon</settlement></placeName></affiliation></author><author><name sortKey="Jorgensen, Christian" sort="Jorgensen, Christian" uniqKey="Jorgensen C" first="Christian" last="Jorgensen">Christian Jorgensen</name><affiliation wicri:level="3"><nlm:affiliation>Clinical Immunology and Osteoarticular Diseases Therapeutic Unit, Lapeyronie University Hospital, Montpellier, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Clinical Immunology and Osteoarticular Diseases Therapeutic Unit, Lapeyronie University Hospital, Montpellier</wicri:regionArea><placeName><region type="region">Occitanie (région administrative)</region><region type="old region">Languedoc-Roussillon</region><settlement type="city">Montpellier</settlement></placeName></affiliation></author><author><name sortKey="Cantagrel, Alain" sort="Cantagrel, Alain" uniqKey="Cantagrel A" first="Alain" last="Cantagrel">Alain Cantagrel</name><affiliation wicri:level="3"><nlm:affiliation>Rhumatologie et Immunologie Clinique, CHU Purpan, Toulouse, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Rhumatologie et Immunologie Clinique, CHU Purpan, Toulouse</wicri:regionArea><placeName><region type="region">Occitanie (région administrative)</region><region type="old region">Midi-Pyrénées</region><settlement type="city">Toulouse</settlement></placeName></affiliation></author><author><name sortKey="Constantin, Arnaud" sort="Constantin, Arnaud" uniqKey="Constantin A" first="Arnaud" last="Constantin">Arnaud Constantin</name><affiliation wicri:level="3"><nlm:affiliation>Rhumatologie et Immunologie Clinique, CHU Purpan, Toulouse, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Rhumatologie et Immunologie Clinique, CHU Purpan, Toulouse</wicri:regionArea><placeName><region type="region">Occitanie (région administrative)</region><region type="old region">Midi-Pyrénées</region><settlement type="city">Toulouse</settlement></placeName></affiliation></author><author><name sortKey="Nigon, Delphine" sort="Nigon, Delphine" uniqKey="Nigon D" first="Delphine" last="Nigon">Delphine Nigon</name><affiliation wicri:level="3"><nlm:affiliation>Rhumatologie et Immunologie Clinique, CHU Purpan, Toulouse, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Rhumatologie et Immunologie Clinique, CHU Purpan, Toulouse</wicri:regionArea><placeName><region type="region">Occitanie (région administrative)</region><region type="old region">Midi-Pyrénées</region><settlement type="city">Toulouse</settlement></placeName></affiliation></author><author><name sortKey="Touitou, Isabelle" sort="Touitou, Isabelle" uniqKey="Touitou I" first="Isabelle" last="Touitou">Isabelle Touitou</name><affiliation wicri:level="3"><nlm:affiliation>Laboratoire de génétique des maladies rares et auto-inflammatoires (Centre de référence), Université Montpellier, CHU Montpellier, Montpellier, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire de génétique des maladies rares et auto-inflammatoires (Centre de référence), Université Montpellier, CHU Montpellier, Montpellier</wicri:regionArea><placeName><region type="region">Occitanie (région administrative)</region><region type="old region">Languedoc-Roussillon</region><settlement type="city">Montpellier</settlement></placeName></affiliation></author><author><name sortKey="Gottenberg, Jacques Eric" sort="Gottenberg, Jacques Eric" uniqKey="Gottenberg J" first="Jacques-Eric" last="Gottenberg">Jacques-Eric Gottenberg</name><affiliation wicri:level="3"><nlm:affiliation>Service de rhumatologie, Hôpital Hautepierre, CHU Strasbourg, Strasbourg, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Service de rhumatologie, Hôpital Hautepierre, CHU Strasbourg, Strasbourg</wicri:regionArea><placeName><region type="region">Grand Est</region><region type="old region">Alsace (région administrative)</region><settlement type="city">Strasbourg</settlement></placeName></affiliation></author><author><name sortKey="Pers, Yves Marie" sort="Pers, Yves Marie" uniqKey="Pers Y" first="Yves-Marie" last="Pers">Yves-Marie Pers</name><affiliation wicri:level="3"><nlm:affiliation>Clinical Immunology and Osteoarticular Diseases Therapeutic Unit, Lapeyronie University Hospital, Montpellier, France. ympers2000@yahoo.fr.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Clinical Immunology and Osteoarticular Diseases Therapeutic Unit, Lapeyronie University Hospital, Montpellier</wicri:regionArea><placeName><region type="region">Occitanie (région administrative)</region><region type="old region">Languedoc-Roussillon</region><settlement type="city">Montpellier</settlement></placeName></affiliation></author></analytic><series><title level="j">The pharmacogenomics journal</title><idno type="eISSN">1473-1150</idno><imprint><date when="2019" type="published">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Alleles</term><term>Antibodies, Monoclonal, Humanized (therapeutic use)</term><term>Antirheumatic Agents (therapeutic use)</term><term>Arthritis, Rheumatoid (drug therapy)</term><term>Arthritis, Rheumatoid (genetics)</term><term>Female</term><term>Genotype</term><term>Humans</term><term>Interleukin-6 (genetics)</term><term>Male</term><term>Middle Aged</term><term>Polymorphism, Single Nucleotide (genetics)</term><term>Receptors, Interleukin-6 (genetics)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Adulte d'âge moyen</term><term>Allèles</term><term>Anticorps monoclonaux humanisés (usage thérapeutique)</term><term>Antirhumatismaux (usage thérapeutique)</term><term>Femelle</term><term>Génotype</term><term>Humains</term><term>Interleukine-6 (génétique)</term><term>Mâle</term><term>Polyarthrite rhumatoïde (génétique)</term><term>Polyarthrite rhumatoïde (traitement médicamenteux)</term><term>Polymorphisme de nucléotide simple (génétique)</term><term>Récepteurs à l'interleukine-6 (génétique)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Interleukin-6</term><term>Receptors, Interleukin-6</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Antibodies, Monoclonal, Humanized</term><term>Antirheumatic Agents</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Arthritis, Rheumatoid</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Arthritis, Rheumatoid</term><term>Polymorphism, Single Nucleotide</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Interleukine-6</term><term>Polyarthrite rhumatoïde</term><term>Polymorphisme de nucléotide simple</term><term>Récepteurs à l'interleukine-6</term></keywords><keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Polyarthrite rhumatoïde</term></keywords><keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>Anticorps monoclonaux humanisés</term><term>Antirhumatismaux</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Alleles</term><term>Female</term><term>Genotype</term><term>Humans</term><term>Male</term><term>Middle Aged</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Adulte d'âge moyen</term><term>Allèles</term><term>Femelle</term><term>Génotype</term><term>Humains</term><term>Mâle</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Biological disease-modifying anti-rheumatic drugs (bDMARDs) have changed care of patients with rheumatoid arthritis (RA). However, bDMARDs are costly, can lead to serious infections, and induce a sustained remission in only 30% of RA patients. In this study, we sought to determine if the clinical response to treatment with Tocilizumab (TCZ), an IL-6 inhibitor, varied with genetic background. The efficacy of TCZ was assessed using the European League Against Rheumatism (EULAR) response criteria, measured after 3 months of treatment in two samples of French RA patients (TOCI and ROC studies). Single nucleotide polymorphisms (SNPs) in 21 candidate genes were genotyped using KasPar method (LGC-genomics, UK) and then analyzed to determine their contribution to variation in the response to treatment. One hundred twenty-three patients in the TOCI group (79.8%) and 48 patients in the ROC group (80%) experienced good or moderate EULAR response. The clinical response to treatment was associated with SNP genotype in the gene IL6R, with patients with the homozygous AA-genotype for rs12083537 (IL6R) showing a significantly better response than homozygous or heterozygous patients with the G allele [TOCI: 87.5% of responders for AA genotype vs. 72.2% for AG or GG genotype (p = 0.018); ROC patients: 89.2% of responders for AA genotype vs. 65.2% for AG or GG genotype, p = 0.044]. A meta-analysis combining data from the two cohorts confirmed the lower response rate in patients carrying a copy of the G allele (OR (95% CI) = 0.35 (0.16-0.61), p = 0.001). No association was found with any of the other SNPs tested.</div></front></TEI><affiliations><list><country><li>France</li></country><region><li>Alsace (région administrative)</li><li>Auvergne-Rhône-Alpes</li><li>Bourgogne</li><li>Bourgogne-Franche-Comté</li><li>Franche-Comté</li><li>Grand Est</li><li>Languedoc-Roussillon</li><li>Midi-Pyrénées</li><li>Occitanie (région administrative)</li><li>Rhône-Alpes</li></region><settlement><li>Besançon</li><li>Dijon</li><li>Grenoble</li><li>Montpellier</li><li>Strasbourg</li><li>Toulouse</li></settlement></list><tree><country name="France"><region name="Occitanie (région administrative)"><name sortKey="Luxembourger, Cecile" sort="Luxembourger, Cecile" uniqKey="Luxembourger C" first="Cécile" last="Luxembourger">Cécile Luxembourger</name></region><name sortKey="Cantagrel, Alain" sort="Cantagrel, Alain" uniqKey="Cantagrel A" first="Alain" last="Cantagrel">Alain Cantagrel</name><name sortKey="Constantin, Arnaud" sort="Constantin, Arnaud" uniqKey="Constantin A" first="Arnaud" last="Constantin">Arnaud Constantin</name><name sortKey="Degboe, Yannick" sort="Degboe, Yannick" uniqKey="Degboe Y" first="Yannick" last="Degboe">Yannick Degboe</name><name sortKey="Gaudin, Philippe" sort="Gaudin, Philippe" uniqKey="Gaudin P" first="Philippe" last="Gaudin">Philippe Gaudin</name><name sortKey="Gottenberg, Jacques Eric" sort="Gottenberg, Jacques Eric" uniqKey="Gottenberg J" first="Jacques-Eric" last="Gottenberg">Jacques-Eric Gottenberg</name><name sortKey="Jorgensen, Christian" sort="Jorgensen, Christian" uniqKey="Jorgensen C" first="Christian" last="Jorgensen">Christian Jorgensen</name><name sortKey="Ladhari, Chayma" sort="Ladhari, Chayma" uniqKey="Ladhari C" first="Chayma" last="Ladhari">Chayma Ladhari</name><name sortKey="Maillefert, Jean Francis" sort="Maillefert, Jean Francis" uniqKey="Maillefert J" first="Jean-Francis" last="Maillefert">Jean-Francis Maillefert</name><name sortKey="Marotte, Hubert" sort="Marotte, Hubert" uniqKey="Marotte H" first="Hubert" last="Marotte">Hubert Marotte</name><name sortKey="Nigon, Delphine" sort="Nigon, Delphine" uniqKey="Nigon D" first="Delphine" last="Nigon">Delphine Nigon</name><name sortKey="Pers, Yves Marie" sort="Pers, Yves Marie" uniqKey="Pers Y" first="Yves-Marie" last="Pers">Yves-Marie Pers</name><name sortKey="Rittore, Cecile" sort="Rittore, Cecile" uniqKey="Rittore C" first="Cécile" last="Rittore">Cécile Rittore</name><name sortKey="Ruyssen Witrand, Adeline" sort="Ruyssen Witrand, Adeline" uniqKey="Ruyssen Witrand A" first="Adeline" last="Ruyssen-Witrand">Adeline Ruyssen-Witrand</name><name sortKey="Touitou, Isabelle" sort="Touitou, Isabelle" uniqKey="Touitou I" first="Isabelle" last="Touitou">Isabelle Touitou</name><name sortKey="Wendling, Daniel" sort="Wendling, Daniel" uniqKey="Wendling D" first="Daniel" last="Wendling">Daniel Wendling</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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