Contribution of HLA-DRB1*04 alleles and anti-cyclic citrullinated antibodies to development of resistance to disease-modifying antirheumatic drugs in early rheumatoid arthritis.
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.
Mori
Shunsuke
S
Clinical Research Center for Rheumatic Disease and Department of Rheumatology, NHO Kumamoto Saishunsou National Hospital, 2659 Suya, Kohshi, Kumamoto 861-1196, Japan. moris@saisyunsou1.hosp.go.jp
Hirose
Jun
J
Yonemura
Kensuke
K
D000368:Aged; D000483:Alleles; D000906:Antibodies / Q000097:blood; D018501:Antirheumatic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D004351:Drug Resistance; D000939:Epitopes / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
D000906:Antibodies; D018501:Antirheumatic Agents; D000939:Epitopes; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C527195:HLA-DRB1*04 antigen; D010456:Peptides, Cyclic; D014409:Tumor Necrosis Factor-alpha; C487763:cyclic citrullinated peptide; D008727:Methotrexate
Arthritis Rheum. 2004 Mar;50(3):709-15
15022309
J Rheumatol. 2002 Dec;29(12):2521-4
12465145
Arthritis Rheum. 2004 Jul;50(7):2113-21
15248208
Arthritis Rheum. 2006 Apr;54(4):1117-21
16572446
J Clin Invest. 1995 May;95(5):2120-6
7738179
Arthritis Rheum. 1988 Mar;31(3):315-24
3358796
Arthritis Rheum. 2002 Apr;46(4):899-905
11953965
Ann Rheum Dis. 2003 Feb;62(2):120-6
12525380
Clin Exp Rheumatol. 1997 Jan-Feb;15(1):53-7
9093773
J Rheumatol. 1997 Dec;24(12):2304-7
9415632
Arthritis Rheum. 2005 Jan;52(1):27-35
15641102
Ann Rheum Dis. 2008 Sep;67(9):1347-50
18388157
Br J Rheumatol. 1997 Jun;36(6):630-6
9236671
Ann Rheum Dis. 2006 Mar;65(3):342-7
16096333
Ann Rheum Dis. 2010 Jan;69(1):222-5
19293160
Rheum Dis Clin North Am. 1992 Nov;18(4):761-83
1280846
Arthritis Rheum. 2000 Jan;43(1):155-63
10643712
Arthritis Res Ther. 2004;6(4):R303-8
15225365
Arthritis Rheum. 1987 Nov;30(11):1205-13
2446635
Clin Rheumatol. 2009 Mar;28(3):277-83
19002544
Rheum Dis Clin North Am. 1992 Nov;18(4):741-59
1280845
Ann Rheum Dis. 2004 Sep;63(9):1090-5
15308518
Arthritis Rheum. 1997 Feb;40(2):341-51
9041946
Ann Rheum Dis. 2007 Jan;66(1):34-45
16396980
Arthritis Res Ther. 2005;7(5):R949-58
16207336
Arthritis Res Ther. 2006;8(4):R128
16859535
J Rheumatol. 2002 Feb;29(2):271-5
11842822
Arthritis Rheum. 2003 Oct;48(10):2741-9
14558078
Arthritis Rheum. 2005 Nov;52(11):3433-8
16255021
Arthritis Rheum. 1991 Jul;34(7):822-30
2059230
Br J Rheumatol. 1995 Nov;34 Suppl 2:43-8
8535649
Ann Rheum Dis. 2006 Mar;65(3):366-71
16014670
Rheumatology (Oxford). 2007 Jan;46(1):100-4
16728439
Rheum Dis Clin North Am. 2002 Feb;28(1):59-78
11840698
J Rheumatol. 2006 Nov;33(11):2120-3
17086601
Arthritis Rheum. 2004 Nov;50(11):3432-43
15529377
Rheum Dis Clin North Am. 2002 Feb;28(1):39-58
11840697
Clin Rheumatol. 2007 Jul;26(7):1111-8
17109060
Arthritis Rheum. 2006 Jan;54(1):26-37
16385520
Arthritis Rheum. 2004 Feb;50(2):400-12
14872482
J Rheumatol. 1995 Jun;22(6):1032-6
7674226
Arthritis Rheum. 2004 Jan;50(1):43-54
14730598
Arthritis Rheum. 2000 Aug;43(8):1831-5
10943873
Arthritis Rheum. 2005 Nov;52(11):3381-90
16258899
Ann Rheum Dis. 2006 Apr;65(4):453-8
16176994