Rheumatology Advance Access originally published online on May 23, 2006
Rheumatology 2007 46(1):93-96; doi:10.1093/rheumatology/kel175
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The –308 tumour necrosis factor-
gene polymorphism predicts therapeutic response to TNF-blockers in rheumatoid arthritis and spondyloarthritis patients
1Department of Rheumatology and Clinical Immunology/Allergology and 2Division of Molecular Diagnostics, University Hospital, Inselspital, Berne, Switzerland.
Correspondence to: Michael Seitz, MD, Department of Rheumatology and Clinical Immunology/Allergology, University Hospital, CH-3010 Berne, Switzerland. E-mail: michael.seitz{at}insel.ch
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Abstract |
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Objective. To examine whether the G-to-A polymorphism at position –308 in the promoter of the tumour necrosis factor-
(TNF) gene influences the therapeutic response to TNF-blockers in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS).
Methods. A total of 54 patients with RA, 10 with PsA and 22 with AS were genotyped by polymerase chain reaction for the –308 TNF promoter polymorphism. They were treated with infliximab (n = 63), adalimumab (n = 10) or etanercept (n = 13). Clinical response was assessed after 24 weeks by the Disease Activity Score in 28 joints (DAS28) for RA and PsA, and the Bath Ankylosing Spondylitis Activity Index (BASDAI) for AS patients.
Results. All patients with the A/A genotype (n = 3, all RA) and two patients with the A/G genotype (AS) failed to respond to anti-TNF treatment. Irrespective of the underlying disease, moderate response (n = 44) was predominantly associated with the A/G genotype (A/G 18/22, G/G 4/22), whereas good response (n = 59) was exclusively seen in patients with the G/G genotype. The average improvement in the DAS28 score was 0.83 in the A/A, 1.50 in the A/G and 2.64 in the G/G group of RA and PsA patients (P < 0.0001). The BASDAI score in AS improved on average by 1.21 in the A/G and by 3.30 in the G/G group (P < 0.005).
Conclusions. The data suggest that humans with a TNF –308 G/G genotype are better responders to anti-TNF treatment than those with A/A or A/G genotypes independent of the treated rheumatic disease (RA, PsA or AS).
KEY WORDS: –308 TNF promoter polymorphism, Response to TNF-blockers
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