Systematic review: accuracy of anti-citrullinated Peptide antibodies for diagnosing rheumatoid arthritis.
BACKGROUND
Early recognition and treatment of rheumatoid arthritis is important to prevent irreversible joint damage. Anti-citrullinated peptide antibodies (ACPA) have been suggested for early diagnosis.


OBJECTIVE
To compare the accuracy of ACPA and rheumatoid factor in diagnosing rheumatoid arthritis in patients with early symptoms of the disease.


METHODS
10 medical databases from inception to September 2009, with no language or publication restrictions, and references of included studies.


METHODS
Two independent reviewers screened searches. Full articles were assessed by one reviewer and checked by a second reviewer to identify studies that reported 2 x 2 data on ACPA for the diagnosis of rheumatoid arthritis (by 1987 American College of Rheumatology criteria).


METHODS
One reviewer abstracted data on patient characteristics, ACPA details, and 2 x 2 data and assessed study quality by using the QUADAS tool. A second reviewer checked extractions.


RESULTS
151 studies were included, with considerable heterogeneity in sensitivity (range, 12% to 93%) and specificity (range, 63% to 100%). In cohort studies that investigated second-generation anti-cyclic citrullinated peptide antibodies (anti-CCP2) in patients with early rheumatoid arthritis (<2 years), summary sensitivity and specificity were 57% (95% CI, 51% to 63%) and 96% (CI, 93% to 97%), respectively. Case-control and cross-sectional studies and studies of patients with established rheumatoid arthritis all overestimated sensitivity. Anti-CCP2 had greater specificity than rheumatoid factor (96% vs. 86%), with similar sensitivity. Evidence was insufficient to ascertain whether the combination of anti-CCP2 and rheumatoid factor provides additional benefit over anti-CCP2 alone.


CONCLUSIONS
Most studies used a diagnostic case-control design, which overestimated sensitivity. Items relating to study quality were rarely reported. Publication bias could not be assessed.


CONCLUSIONS
Anti-CCP2 should be included in the work-up of patients with early symptoms of rheumatoid arthritis.
Whiting
Penny F
PF
Department of Social Medicine, University of Bristol, Canynge Hall, 39 Whatley Road, Bristol BS8 2PS, United Kingdom. penny.whiting@bristol.ac.uk
Smidt
Nynke
N
Sterne
Jonathan A C
JA
Harbord
Roger
R
Burton
Anya
A
Burke
Margaret
M
Beynon
Rebecca
R
Ben-Shlomo
Yoav
Y
Axford
John
J
Dieppe
Paul
P
D001172:Arthritis, Rheumatoid / Q000175:diagnosis* / Q000276:immunology; D001323:Autoantibodies / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D010456:Peptides, Cyclic / Q000276:immunology*; D012680:Sensitivity and Specificity
D001323:Autoantibodies; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide