Arthritis development in patients with arthralgia is strongly associated with anti-citrullinated protein antibody status: a prospective cohort study.
BACKGROUND
Anti-citrullinated protein antibodies (ACPA) are associated with increased risk for rheumatoid arthritis.


OBJECTIVE
To investigate the effect of the presence and levels of ACPA on arthritis development in patients with arthralgia.


METHODS
Patients with arthralgia positive for ACPA or IgM rheumatoid factor (IgM-RF) were tested for the shared epitope (SE) and were prospectively followed up for at least 12 months. Absence of clinical arthritis at inclusion and arthritis development during follow-up were independently confirmed by two investigators. Cox regression hazard analyses were used to calculate hazard ratios (HRs) for arthritis development.


RESULTS
147 patients with arthralgia were included (50 ACPA positive, 52 IgM-RF positive and 45 positive for both antibodies). After a median follow-up of 28 months (interquartile range (IQR) 19-39), 29 patients developed arthritis in a median of 4 (IQR 3-6) joints and 26 (90%) of these were ACPA positive. The presence of ACPA (HR = 6.0; 95% confidence interval (95% CI) 1.8 to 19.8; p = 0.004), but not of IgM-RF (HR = 1.4, 95% CI 0.6 to 3.1) nor the SE (HR = 1.5, 95% CI 0.7 to 3.0), was associated with arthritis development. Within the group of ACPA-positive patients, the risk for arthritis was enhanced by the presence of IgM-RF (HR = 3.0; 95% CI 1.4 to 6.9; p = 0.01) and high ACPA levels (HR = 1.7; 95% CI 1.1 to 2.5; p = 0.008), but not the SE (HR = 1.0; 95% CI 0.5 to 2.1; p = 1.0).


CONCLUSIONS
In patients with arthralgia the presence of ACPA (but not of IgM-RF or SE) predicts arthritis development. The risk in ACPA-positive patients may be further increased by the concomitant presence of IgM-RF or high levels of ACPA.
Jan van Breemen Instituut, Amsterdam, The Netherlands.
W H
WH
Bos
G J
GJ
Wolbink
M
M
Boers
G J
GJ
Tijhuis
N
N
de Vries
I E
IE
van der Horst-Bruinsma
P P
PP
Tak
R J
RJ
van de Stadt
C J
CJ
van der Laken
B A C
BA
Dijkmans
D
D
van Schaardenburg
D018771:Arthralgia / Q000276:immunology* / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000378:metabolism; D004812:Epidemiologic Methods; D000939:Epitopes / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology* / Q000378:metabolism; D012217:Rheumatoid Factor / Q000276:immunology* / Q000378:metabolism
D000939:Epitopes; D007075:Immunoglobulin M; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide; D012217:Rheumatoid Factor