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Pharmacogenomics J. 2019 Aug;19(4):368-374. doi: 10.1038/s41397-019-0072-6. Epub 2019 Jan 16.

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

Author information

1
Rhumatologie et Immunologie Clinique, CHU Purpan, Toulouse, France.
2
Clinical Immunology and Osteoarticular Diseases Therapeutic Unit, Lapeyronie University Hospital, Montpellier, France.
3
Laboratoire de génétique des maladies rares et auto-inflammatoires (Centre de référence), Université Montpellier, CHU Montpellier, Montpellier, France.
4
Service de Rhumatologie, Hôpital Bocage, CHU Dijon, Dijon, France.
5
Service de Rhumatologie, Hôpital Sud, CHU Grenoble, Grenoble, France.
6
Rhumatologie, CHU Saint Etienne, Saint-Priest-en-Jarez, France.
7
SAINBIOSE, INSERM U1059, University of Lyon, 42023, Saint-Etienne, France.
8
Rhumatologie, CHRU de Besançon, Besançon, France.
9
EA4266 Université de Franche-Comté, Besançon, France.
10
IRMB, INSERM, Université Montpellier, Montpellier, France.
11
Service de rhumatologie, Hôpital Hautepierre, CHU Strasbourg, Strasbourg, France.
12
Clinical Immunology and Osteoarticular Diseases Therapeutic Unit, Lapeyronie University Hospital, Montpellier, France. ympers2000@yahoo.fr.
13
IRMB, INSERM, Université Montpellier, Montpellier, France. ympers2000@yahoo.fr.

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.

PMID:
30647443
DOI:
10.1038/s41397-019-0072-6

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