Effects of polymorphisms in TRAILR1 and TNFR1A on the response to anti-TNF therapies in patients with rheumatoid and psoriatic arthritis.

OBJECTIVES: As the role of polymorphisms in death receptors (DRs) such as Tumor Necrosis Factor-related Apoptosis-inducing Ligand Receptor 1 (TRAIL-R1) and Tumor Necrosis Factor Receptor 1A (TNF-R1A) on the response to anti-TNF therapy remains unknown, we evaluated the association between TRAILR1 and TNFR1A gene polymorphisms (rs20575/C626G and rs767455/G36A) and the pharmacogenetics of patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) treated with TNFα blockers.

METHODS: One hundred and forty-five patients (90 RA and 55 PsA) treated with anti-TNFα therapy (RA: 75 infliximab, 8 etanercept, 7 adalimumab. PsA: 27 infliximab, 19 etanercept, 9 adalimumab) were genotyped for TRAILR1 and TNFR1A polymorphisms by allelic discrimination. The response to anti-TNFα was assessed by EULAR criteria.

RESULTS: In RA, the TRAILR1 CC genotype was associated with a better response after 3 and 6 months of anti-TNFα treatment (CC: 91.7% vs. CG/GG: 62.2%; P=0.019, and CC: 82.6% vs. CG/GG: 56.1%; P=0.019, respectively). Similar results were observed in only infliximab-treated RA patients. With respect to the TNFR1A polymorphism, there was an association between the AA genotype and a poorer response at 3 months in RA patients (AA: 39.3% vs.

AG/GG: 19.0%; P=0.04). In PsA, TRAILR1 CC genotype was only associated with EULAR response to infliximab at 6 months (CC: 71.4% vs CG/GG: 50%P=0.048). In contrast to RA, the TNFR1 polymorphism in PsA was associated with a better response at 3 months (AA 88% vs AG/GG 58.9%; P=0.04).

CONCLUSIONS: This study provides the first evidence that a polymorphism in TRAILR1 influences the response to anti-TNFα therapy in RA and also suggests that TNFR1A polymorphism may have opposing effects on the response to anti-TNFα in RA and PsA.