PMID- 20383728
OWN - NLM
STAT- MEDLINE
DCOM- 20110217
LR  - 20211020
IS  - 1434-9949 (Electronic)
IS  - 0770-3198 (Linking)
VI  - 29
IP  - 12
DP  - 2010 Dec
TI  - Contribution of HLA-DRB1*04 alleles and anti-cyclic citrullinated antibodies to 
      development of resistance to disease-modifying antirheumatic drugs in early 
      rheumatoid arthritis.
PG  - 1357-66
LID - 10.1007/s10067-010-1454-y [doi]
AB  - 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 alpha (TNFalpha) 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-TNFalpha agents in patients with early RA.
FAU - Mori, Shunsuke
AU  - Mori S
AD  - 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
FAU - Hirose, Jun
AU  - Hirose J
FAU - Yonemura, Kensuke
AU  - Yonemura K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100411
PL  - Germany
TA  - Clin Rheumatol
JT  - Clinical rheumatology
JID - 8211469
RN  - 0 (Antibodies)
RN  - 0 (Antirheumatic Agents)
RN  - 0 (Epitopes)
RN  - 0 (HLA-DR Antigens)
RN  - 0 (HLA-DRB1 Chains)
RN  - 0 (HLA-DRB1*04 antigen)
RN  - 0 (Peptides, Cyclic)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (cyclic citrullinated peptide)
RN  - YL5FZ2Y5U1 (Methotrexate)
SB  - IM
MH  - Aged
MH  - Alleles
MH  - Antibodies/blood
MH  - Antirheumatic Agents/pharmacology/*therapeutic use
MH  - Arthritis, Rheumatoid/*drug therapy/genetics/immunology
MH  - Drug Resistance
MH  - Epitopes/genetics
MH  - Female
MH  - Gene Frequency
MH  - HLA-DR Antigens/*genetics
MH  - HLA-DRB1 Chains
MH  - Humans
MH  - Male
MH  - Methotrexate/*therapeutic use
MH  - Middle Aged
MH  - Peptides, Cyclic/*immunology
MH  - Treatment Outcome
MH  - Tumor Necrosis Factor-alpha/antagonists & inhibitors
EDAT- 2010/04/13 06:00
MHDA- 2011/02/18 06:00
CRDT- 2010/04/13 06:00
PHST- 2009/10/13 00:00 [received]
PHST- 2010/03/24 00:00 [accepted]
PHST- 2010/02/24 00:00 [revised]
PHST- 2010/04/13 06:00 [entrez]
PHST- 2010/04/13 06:00 [pubmed]
PHST- 2011/02/18 06:00 [medline]
AID - 10.1007/s10067-010-1454-y [doi]
PST - ppublish
SO  - Clin Rheumatol. 2010 Dec;29(12):1357-66. doi: 10.1007/s10067-010-1454-y. Epub 
      2010 Apr 11.