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AB0293 High Serum Levels of Anti-Cyclic Citrullinated Peptide Antibody and Matrix Metalloproteinase-3 at the Time of Diagnosis of Rheumatoid Arthritis Are Possible Predictors of Future Initiation of Biological Agents
  1. M. Kono1,2,
  2. T. Odani1,2,
  3. K. Hiura3,
  4. S. Fukaya1,
  5. K. Oba4,
  6. T. Takeda1,
  7. H. Kikuchi1,
  8. S. Iwaki-Egawa5,
  9. T. Atsumi2
  1. 13rd Department of Internal medicine, Hokkaido P.W.F.A.C Obihiro-Kosei General Hospital, Obihiro
  2. 2Division of Rheumatology, Endocrinology and Nephrology, Hokkaido University Graduate School of Medicine, Sapporo
  3. 3Department of pharmacy, Hokkaido P.W.F.A.C Abashiri-Kosei General Hospital, Abashiri
  4. 4Department of Biostatistics, School of Public Health, Graduate School of Medicine, the University of Tokyo, Tokyo
  5. 5Division of Life Science, Hokkaido Pharmaceutical University School of Pharmacy, Sapporo, Japan


Background Damage to bones is accelerated massively during the first two years after developing rheumatoid arthritis (RA), thus the patients with poor response to csDMARDs need early intervention by biological agents (Bio). However, few markers have been established for the prediction of future use of Bio on the diagnosis as RA.

Objectives To clarify the predictors of future initiation of Bio at the time of RA diagnosis.

Methods One hundred five consecutive new outpatients complaining arthralgia without definite diagnosis of RA were included at 3rd Department of Internal medicine clinic at Hokkaido P.W.F.A.C Obihiro-Kosei General Hospital from December 2012 to September 2013. The subjects classified as RA, fulfilling the criteria of 2010 American College of Rheumatology/European League Against Rheumatism, were treated by standard protocol and followed until December 2014 to discriminate Bio user from non-Bio user. The observation period until the initiation of Bio was registered.

Results Among 105 patients, 49 were classified as having RA by the criteria. Out of 49 patients, four patients were excluded due to their ineligibility (two patients on prednisone at the time of RA diagnosis, one on over 20 mg/day prednisone due to interstitial lung disease during observation period, and one with less than three months' observation period). At the time of RA diagnosis, mean age was 60±15 years old and the median disease duration was 20 (range: 3.5-24.8) months. Mean Disease Activity Score 28-ESR was 5.0±1.3, median simplified disease activity index 17.1 (5.7-71.9), anti-cyclic citrullinated peptide antibody (ACPA) 42 (0.6-500) U/ml, rheumatoid factor 67 (4-1580) mg/dl, matrix metalloproteinase-3 (MMP-3) 80 (24-1515) ng/ml, and CRP 0.45 (0.01-10.47) mg/dl. During observation period, 14 patients were initiated Bio. Multivariate analysis with Cox's proportional hazards model showed that ACPA (HR for every 50 U/ml, 1.26, 95%C.I. 1.05-1.50, p=0.01) and MMP-3 (HR for every 50 ng/ml, 1.15, 95%C.I. 1.01-1.30, p=0.03) are statistically significant risk factors for Bio users. We determined cutoff points of ACPA and MMP-3 using the receiver operatorating characteristic curves and we decided ACPA ≥250 U/ml and MMP-3 ≥200 ng/ml were risk factors. Log-rank test showed the more risk factors the patients have, the higher risk for initiation of Bio (Figure 1, p<0.001).

Conclusions High serum levels of ACPA and MMP-3 at the time of diagnosis of RA are possible predictors of future Bio user.

Disclosure of Interest None declared

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