Contribution of HLA-DRB1*04 alleles and anti-cyclic citrullinated antibodies to development of resistance to disease-modifying antirheumatic drugs in early rheumatoid arthritis
Identifieur interne : 001734 ( Main/Exploration ); précédent : 001733; suivant : 001735Contribution of HLA-DRB1*04 alleles and anti-cyclic citrullinated antibodies to development of resistance to disease-modifying antirheumatic drugs in early rheumatoid arthritis
Auteurs : Shunsuke Mori [Japon] ; Jun Hirose [Japon] ; Kensuke Yonemura [Japon]Source :
- Clinical Rheumatology [ 0770-3198 ] ; 2010-12-01.
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Abstract
Abstract: This study was intended to evaluate HLA-DRB1 alleles and antibodies against anti-cyclic citrullinated peptides (anti-CCP Abs) for their value in predicting patient responses to treatment with disease-modifying antirheumatic drugs (DMARDs) in early rheumatoid arthritis (RA). The subjects were 124 Japanese patients who had received their first treatment with DMARDs, usually methotrexate, within 1 year of disease onset and who had been followed-up for 2 years subsequently. Approximately 40% of patients developed DMARD resistance and accordingly required anti-tumor necrosis factor α (TNFα) therapy during the 2-year period. DMARD resistance was strongly associated with the carriage of SE-positive HLA-DRB1*04 alleles, especially the *0405 allele (OR, 3.92; 95%CI, 1.83–8.41; p = 0.0003). In contrast, the SE-positive allele HLA-DRB1*0101 was less potent in contributing to DMARD resistance. The rate of anti-CCP Ab-positive patients was significantly higher in the DMARD-resistant group (OR, 6.62; 95%CI, 1.45–30.24; p = 0.008). Multivariate logistic regression analysis confirmed the strong association of DMARD resistance with the presence of SE-positive *04 alleles (OR, 2.89; 95%CI, 1.28–6.53; p = 0.011) and anti-CCP Abs (OR, 6.31; 95%CI, 1.23–32.34; p = 0.027), yielding an area under the receiver operating characteristic curve of 0.76 (95% CI, 0.68–0.84; p = 0.000). After stratification, the highest rate of DMARD resistance was observed in patients having both SE-positive *04 alleles and anti-CCP Abs. These observations show that the presence of SE-positive *04 alleles in combination with anti-CCP Abs is the strongest predictor for development of DMARD resistance and eventual need of anti-TNFα agents in patients with early RA.
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DOI: 10.1007/s10067-010-1454-y
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The subjects were 124 Japanese patients who had received their first treatment with DMARDs, usually methotrexate, within 1 year of disease onset and who had been followed-up for 2 years subsequently. Approximately 40% of patients developed DMARD resistance and accordingly required anti-tumor necrosis factor α (TNFα) therapy during the 2-year period. DMARD resistance was strongly associated with the carriage of SE-positive HLA-DRB1*04 alleles, especially the *0405 allele (OR, 3.92; 95%CI, 1.83–8.41; p = 0.0003). In contrast, the SE-positive allele HLA-DRB1*0101 was less potent in contributing to DMARD resistance. The rate of anti-CCP Ab-positive patients was significantly higher in the DMARD-resistant group (OR, 6.62; 95%CI, 1.45–30.24; p = 0.008). Multivariate logistic regression analysis confirmed the strong association of DMARD resistance with the presence of SE-positive *04 alleles (OR, 2.89; 95%CI, 1.28–6.53; p = 0.011) and anti-CCP Abs (OR, 6.31; 95%CI, 1.23–32.34; p = 0.027), yielding an area under the receiver operating characteristic curve of 0.76 (95% CI, 0.68–0.84; p = 0.000). After stratification, the highest rate of DMARD resistance was observed in patients having both SE-positive *04 alleles and anti-CCP Abs. These observations show that the presence of SE-positive *04 alleles in combination with anti-CCP Abs is the strongest predictor for development of DMARD resistance and eventual need of anti-TNFα agents in patients with early RA.</div></front></TEI><affiliations><list><country><li>Japon</li></country></list><tree><country name="Japon"><noRegion><name sortKey="Mori, Shunsuke" sort="Mori, Shunsuke" uniqKey="Mori S" first="Shunsuke" last="Mori">Shunsuke Mori</name></noRegion><name sortKey="Hirose, Jun" sort="Hirose, Jun" uniqKey="Hirose J" first="Jun" last="Hirose">Jun Hirose</name><name sortKey="Mori, Shunsuke" sort="Mori, Shunsuke" uniqKey="Mori S" first="Shunsuke" last="Mori">Shunsuke Mori</name><name sortKey="Yonemura, Kensuke" sort="Yonemura, Kensuke" uniqKey="Yonemura K" first="Kensuke" last="Yonemura">Kensuke Yonemura</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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