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A single nucleotide polymorphism of IL6-receptor is associated with response to tocilizumab in rheumatoid arthritis patients

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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.

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Authors and Affiliations

  1. Rhumatologie et Immunologie Clinique, CHU Purpan, Toulouse, France

    Cécile Luxembourger, Adeline Ruyssen-Witrand, Yannick Degboe, Alain Cantagrel, Arnaud Constantin & Delphine Nigon

  2. Clinical Immunology and Osteoarticular Diseases Therapeutic Unit, Lapeyronie University Hospital, Montpellier, France

    Chayma Ladhari, Christian Jorgensen & Yves-Marie Pers

  3. Laboratoire de génétique des maladies rares et auto-inflammatoires (Centre de référence), Université Montpellier, CHU Montpellier, Montpellier, France

    Cécile Rittore & Isabelle Touitou

  4. Service de Rhumatologie, Hôpital Bocage, CHU Dijon, Dijon, France

    Jean-Francis Maillefert

  5. Service de Rhumatologie, Hôpital Sud, CHU Grenoble, Grenoble, France

    Philippe Gaudin

  6. Rhumatologie, CHU Saint Etienne, Saint-Priest-en-Jarez, France

    Hubert Marotte

  7. SAINBIOSE, INSERM U1059, University of Lyon, 42023, Saint-Etienne, France

    Hubert Marotte

  8. Rhumatologie, CHRU de Besançon, Besançon, France

    Daniel Wendling

  9. EA4266 Université de Franche-Comté, Besançon, France

    Daniel Wendling

  10. IRMB, INSERM, Université Montpellier, Montpellier, France

    Christian Jorgensen, Isabelle Touitou & Yves-Marie Pers

  11. Service de rhumatologie, Hôpital Hautepierre, CHU Strasbourg, Strasbourg, France

    Jacques-Eric Gottenberg

Authors
  1. Cécile Luxembourger
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  2. Adeline Ruyssen-Witrand
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  3. Chayma Ladhari
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  9. Daniel Wendling
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Correspondence to Yves-Marie Pers.

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Luxembourger, C., Ruyssen-Witrand, A., Ladhari, C. et al. A single nucleotide polymorphism of IL6-receptor is associated with response to tocilizumab in rheumatoid arthritis patients. Pharmacogenomics J 19, 368–374 (2019). https://doi.org/10.1038/s41397-019-0072-6

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