RESEARCH Polymorphisms Influence Response to RA Therapy

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Polymorphisms Influence Response to RA Therapy

NEW YORK (Reuters Health) Sept 13 - Genetic variations in particular HLA and

TNF gene regions predict response to methotrexate and etanercept in patients

with early rheumatoid arthritis (RA), researchers report in the September

issue of Arthritis and Rheumatology.

Dr. S. Louis Bridges Jr., of the University of Alabama at Birmingham, and

colleagues analyzed genetic and clinical data from 457 patients who had had

RA for 3 years or less. The subjects had been randomized to methotrexate

(weekly), low-dose etanercept (10 mg twice weekly) or standard-dose

etanercept (25 mg twice weekly).

An improvement of 50% on The American College of Rheumatology disease

activity score was the main outcome measure.

Patients who had inherited two copies of the HLA-DRB1 alleles encoding the

shared epitope which influences susceptibility to and severity of RA were

4.3 times more likely to show a response to standard-dose etanercept than

were those with one or no copy.

In total, 76% of the patients with two shared epitope copies responded to

standard-dose etanercept versus a 46% response to methotrexate. However,

responses to treatment with low-dose etanercept or methotrexate did not

differ significantly by the number of shared epitope copies

Among the Caucasian subjects, extended haplotypes that included the HLA-DRB1

alleles and LTA-TNF variants were also associated with treatment response,

the team notes.

These results, the researchers conclude, may be of use in identifying which

patients " are more likely to benefit from treatment with methotrexate or

etanercept. "

Moreover, Dr. Bridges told Reuters Health that the possible " genetic

influences on treatment responses in rheumatoid arthritis...should be

confirmed in additional studies and in individuals of different race and

ethnicity. "

Arthritis Rheum 2004;50:2750-2756.