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Contribution of HLA-DRB1*04 alleles and anti-cyclic citrullinated antibodies to development of resistance to disease-modifying antirheumatic drugs in early rheumatoid arthritis

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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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Acknowledgments

This study was supported by research funds from the National Hospital Organization (NHO), Japan.

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Authors and Affiliations

  1. Clinical Research Center for Rheumatic Disease and Department of Rheumatology, NHO Kumamoto Saishunsou National Hospital, 2659 Suya, Kohshi, Kumamoto, 861-1196, Japan

    Shunsuke Mori

  2. Department of Medical Information Science and Administration Planning, Kumamoto University Hospital, Kumamoto, Japan

    Jun Hirose

  3. Clinical Research Center for Rheumatic Disease and Department of Orthopedic Surgery, NHO Kumamoto Saishunsou National Hospital, Kumamoto, Japan

    Kensuke Yonemura

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  1. Shunsuke Mori
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  2. Jun Hirose
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  3. Kensuke Yonemura
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Correspondence to Shunsuke Mori.

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Mori, S., Hirose, J. & Yonemura, K. Contribution of HLA-DRB1*04 alleles and anti-cyclic citrullinated antibodies to development of resistance to disease-modifying antirheumatic drugs in early rheumatoid arthritis. Clin Rheumatol 29, 1357–1366 (2010). https://doi.org/10.1007/s10067-010-1454-y

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  • DOI: https://doi.org/10.1007/s10067-010-1454-y

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