RESEARCH - Arthritis development in arthralgia patients is strongly associated with anti-CCP antibody status

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Ann Rheum Dis. Published Online First: 9 April 2009.

doi:10.1136/ard.2008.105759

BMJ Publishing Group Ltd & European League Against Rheumatism.

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Extended Report

Arthritis development in arthralgia patients is strongly associated

with anti-citrullinated protein antibody status: a prospective cohort

study

Wouter H Bos 1, Gerrit Jan Wolbink 1, Maarten Boers 2, Gerard J

Tijhuis 1, Niek de Vries 3, Irene E van der Horst-Bruinsma 2, P

Tak 3, Rob van de Stadt 1, Conny J van der Laken 2, Ben A C Dijkmans 2

and Dirkjan van Schaardenburg 1*

1 Jan van Breemen Instituut, Netherlands

2 VU University Medical Center, Netherlands

3 AMC/University of Amsterdam, Department of Clinical Immunology &

Rheumatology, Netherlands

Abstract

Background: Anti-citrullinated protein antibodies (ACPA) are

associated with increased risk for rheumatoid arthritis. We

prospectively investigated the effect of ACPA presence and levels on

arthritis development in arthralgia patients.

Methods: Arthralgia patients positive for ACPA or IgM rheumatoid

factor (IgM-RF) were tested for the shared epitope (SE) and were

prospectively followed for at least 12 months. Absence of clinical

arthritis at inclusion and arthritis development during follow-up were

independently confirmed by two investigators. -regression hazard

analyses were used to calculate hazard ratios (HR) for arthritis

development.

Results: 147 arthralgia patients were included (52 ACPA positive, 50

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] 1.8-20.1; P = 0.003), but not of IgM-RF (HR 1.4, 95%

CI 0.6-3.1) nor the SE (HR 1.5, 95% CI 0.7-3.0) 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 1.3-6.9; P = 0.01 and high ACPA levels (HR 1.7; 95% CI 1.1-2.5; P =

0.008), but not the SE (HR 1.0; 95% C.I. 0.5-2.1; P = 1.0).

Conclusion: In arthralgia patients 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.

http://ard.bmj.com/cgi/content/abstract/ard.2008.105759v1?papetoc

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