Background Due to the wide range of highly specific and effective biologicals for the treatment of RA it has become of great importance to identify biomarkers for the prediction of therapy outcome, supporting an individualized therapy. Most studies in this field analysed potential markers for a single biological or substance group, respectively.
Objectives In this study we analysed the association of the single nucleotide polymorphism (SNP) rs10414216 in the MED29 gene with the outcome of two different therapeutic approaches.
Methods We studied 275 RA patients treated first with the TNF-blocker etanercept (ETN) and a subgroup of 61 patients treated later in the course of the disease with rituximab (RTX), directed against B-cells. The frequency of the MED29 C/T polymorphism was analysed using a validated TaqMan™ genotyping assay. Disease activity and therapy response were assessed according to the EULAR improvement criteria (http://www.das-score.nl). The primary response of the ETN therapy was assessed 3-4 months after initiation of therapy, the outcome of rituximab after 4-6 months after the first infusion of RTX.
Results The genotype distribution of the SNP MED29 C/T in 275 investigated RA patients was similar compared to healthy controls. There were no differences in the genotype frequencies in association to CCP-antibody positivity. The disease activity at baseline before start of ETN or RTX treatment was comparable for all genotypes. After 3-4 months of ETN treatment the DAS28 decreased by 1.670±1.377, 2.083±1.348 and 2.382±1.286 (mean±SD) for the C/C, C/T and T/T genotypes, respectively. The improvement of the DAS28 was significantly better for the T/T genotype compared to C/C (p=0.003). 58% of T/T carriers but only 27.2% of the C/C carriers were identified as good responders to ETN. However, in RTX treated patients the carriage of the C/C genotype was identified as a predictor for a better response, after 4-6 months the DAS28 decreased by 2.277±1.558 for the C/C genotype compared to 1.310±1.347 for the C/T genotype (p=0,025). 46.2% of C/C and only 27.3% of C/T carriers were good responders to RTX. The T/T carriers were underrepresented in the RTX subgroup, probably as a result of a better outcome of the TNF-blocker therapy in these patients.
Conclusions Our data clearly indicate that a single SNP has the potential to predict the outcome to different therapeutic approaches. The functional importance of this genetic variation has not yet been characterized. However, this SNP is located in the gene region of MED29, a subunit of the mediator complex which plays a substantial role in the regulation of gene expression. Further analysis of this SNP and the respective gene locus could provide further insight into the mechanisms which determine the outcome of different targeted therapies.
Disclosure of Interest None Declared
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