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TNF Gene Polymorphisms Linked to Adalimumab Response in Rheumatoid Arthritis
NEW YORK (Reuters Health) Apr 15 - In patients with rheumatoid arthritis (RA), a single tumor necrosis factor (TNF) haplotype involving three genetic polymorphisms influences response to therapy with the TNF-blocker adalimumab, according to French researchers.
This study, senior investigator Dr. Xavier Mariette told Reuters Health, "provides preliminary data indicating that a single TNF locus haplotype ... when carried on both chromosomes, is associated with a lower response to adalimumab than in patients with other haplotypes."
Dr. Mariette of Hopital de Bicetre, Paris and colleagues examined data on 388 patients taking part in a study of rheumatoid arthritis treatment. They were being treated with adalimumab alone or along with methotrexate or another disease-modifying antirheumatic drug, the team notes in the April issue of the Annals of the Rheumatic Diseases.
Patients were genotyped for HLA-DRB1 and the TNF polymorphisms -238A/G, -308A/G and -857C/T.
Overall, after 12 weeks of therapy, 151 patients (40%) achieved an ACR50 response.
The researchers found that the GGC TNF haplotype (i.e., -238G/-308G/-857C), in homozygous form, was associated with reduced response to adalimumab.
In carriers, who accounted for more than half of the patients, the ACR50 response at 12 weeks was 34% versus 50% for those without the haplotype.
"Surprisingly," say the investigators, the lower response rate was seen mainly in the patients who received adalimumab along with methotrexate.
These results, added Dr. Mariette, "are preliminary and have to be replicated." In addition, he and his colleagues stress that because the difference in ACR50 was relatively small, these findings will not lead to patients being excluded from treatment with adalimumab.
Ann Rheum Dis 2008;67:478-484.
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