RESEARCH - The influence of genetic variation on the response to treatment of early RA with MTX or Enbrel

[Guest guest]

Arthritis Rheum. 2004 Sep;50(9):2750-6.

The influence of genetic variation in the HLA-DRB1 and LTA-TNF regions

on the response to treatment of early rheumatoid arthritis with

methotrexate or etanercept.

Criswell LA, Lum RF, KN, Woehl B, Zhu Y, Wang J, Tiwari HK,

Edberg JC, RP, Moreland LW, Seldin MF, Bridges SL Jr.

lind Medical Research Center for Arthritis, University of

California, San Francisco, CA, USA.

OBJECTIVE: To examine the roles of specific genetic polymorphisms as

predictors of response to treatment of early rheumatoid arthritis (RA).

METHODS: Subjects included 457 patients with early RA (duration of < or

=3 years) who participated in a randomized controlled trial comparing

weekly methotrexate and 2 dosages of etanercept (10 mg twice weekly and

25 mg twice weekly). Our primary outcome measure was achievement of 50%

improvement in disease activity according to the criteria of the

American College of Rheumatology (ACR50 response) after 12 months of

treatment. Subjects were genotyped for HLA-DRB1 alleles and

polymorphisms in the following genes: TNF, LTA, TNFRSF1A, TNFRSF1B,

FCGR2A, FCGR3A, and FCGR3B. Univariate and multivariate analyses were

performed to define the impact of specific polymorphisms and haplotypes

on response to treatment. Covariates for the multivariate analyses

included sex, ethnicity, age, disease duration, and baseline values for

rheumatoid factor and the tender and swollen joint counts. RESULTS: The

presence of 2 HLA-DRB1 alleles encoding the shared epitope (SE)

(compared with 1 or 0 copies) was associated with response to treatment

with standard-dose etanercept (odds ratio [OR] 4.3, 95% confidence

interval [95% CI] 1.8-10.3). Among Caucasian patients, 2 extended

haplotypes that included the HLA-DRB1 alleles *0404 and *0101 (both of

which encode the SE) and 6 single-nucleotide polymorphisms in the

LTA-TNF region were associated with response to treatment. In a

multivariate model that included treatment received and the

aforementioned covariates, the ORs for the association of these

haplotypes with achievement of an ACR50 response at 12 months were 2.5

(95% CI 0.8-7.3) and 4.9 (95% CI 1.5-16.1) for the *0404- and

*0101-containing haplotypes, respectively.

CONCLUSION: Genetic variation in the HLA-DRB1 and the LTA-TNF regions is

significantly associated with response to treatment of early RA. These

findings may have clinical application through the identification of

patients who are most likely to benefit from treatment with methotrexate

or etanercept.

PMID: 15457442

I'll tell you where to go!

Mayo Clinic in Rochester

http://www.mayoclinic.org/rochester

s Hopkins Medicine

http://www.hopkinsmedicine.org