Value of anti-modified citrullinated vimentin and third-generation anti-cyclic citrullinated peptide compared with second-generation anti-cyclic citrullinated peptide and rheumatoid factor in predicting disease outcome in undifferentiated arthritis and rheumatoid arthritis.
OBJECTIVE
Autoantibodies such as rheumatoid factor (RF) and anti-citrullinated protein autoantibodies (ACPAs) determined by testing with second-generation anti-cyclic citrullinated peptide (anti-CCP-2) are frequently measured in clinical practice because of their association with disease outcome in undifferentiated arthritis (UA) and rheumatoid arthritis (RA). Recently, 2 new ACPA tests were developed: third-generation anti-CCP (anti-CCP-3) and anti-modified citrullinated vimentin (anti-MCV) autoantibody tests. To facilitate the decision on which autoantibody to test in daily practice, this study evaluated the capability of these autoantibodies and combinations of them to predict 3 outcome measures: progression from UA to RA, the rate of joint destruction in RA, and the chance of achieving sustained disease-modifying antirheumatic drug (DMARD)-free remission in RA.


METHODS
Patients with UA (n=625) were studied for whether UA progressed to RA after 1 year. Patients with RA (n=687) were studied for whether sustained DMARD-free remission was achieved and for the rate of joint destruction during a median followup of 5 years. Positive predictive values (PPVs) for RA development and for associations with the disease course in RA were compared between single tests (anti-CCP-2, anti-CCP-3, anti-MCV, and RF) and between combinations of these tests.


RESULTS
Among the single tests performed in patients with UA, anti-CCP-2 tended to have the highest PPV for RA development (67.1%), but the 95% confidence intervals of the other tests overlapped. Among the single tests in patients with RA, all 4 tests showed comparable associations with the rate of joint destruction and with the achievement of remission. In both ACPA-positive and ACPA-negative RA, the presence of RF was not associated with more joint destruction. For all outcome measures, performing combinations of 2 or 3 autoantibody tests did not increase the predictive accuracy compared with performing a single test.


CONCLUSIONS
For clinical practice, a single autoantibody test is sufficient for risk estimation in UA and RA.
van der Linden
Michael P M
MP
Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands. M.P.M.van_der_Linden@lumc.nl
van der Woude
Diane
D
Ioan-Facsinay
Andreea
A
Levarht
E W Nivine
EW
Stoeken-Rijsbergen
Gerrie
G
Huizinga
Tom W J
TW
Toes
René E M
RE
van der Helm-van Mil
Annette H M
AH
D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology; D001323:Autoantibodies / Q000097:blood*; D018450:Disease Progression; D000939:Epitopes / Q000276:immunology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000097:blood* / Q000276:immunology; D011237:Predictive Value of Tests; D011379:Prognosis; D012074:Remission Induction; D012217:Rheumatoid Factor / Q000097:blood*; D014746:Vimentin / Q000097:blood* / Q000276:immunology
D018501:Antirheumatic Agents; D001323:Autoantibodies; D000939:Epitopes; D010456:Peptides, Cyclic; D014746:Vimentin; C487763:cyclic citrullinated peptide; D012217:Rheumatoid Factor