RESEARCH - Anti-CCP plus RF may help find patients in the treatment-window stage of early RA

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Anti-CCP plus RF may help find patients in the " treatment-window " stage of

early RA

Rheumawire

Feb 25, 2005

Janis

Birmingham, UK - Patients with newly developed joint inflammation who have

both rheumatoid factor (RF) and antibodies to cyclic citrullinated peptide

(anti-CCP) are at high risk for progression to persistent rheumatoid

arthritis (RA), Dr Karim Raza (MRC Centre for Immune Regulation, Birmingham,

UK) reports in the February 2005 issue of the Journal of Rheumatology [1].

This combination of markers might help identify patients for clinical

studies of very early disease-modifying therapy.

" There is increasing interest in the concept that the very early phase of

clinically apparent RA (within the first 3 months of symptom onset) may

represent a therapeutic window of opportunity. The problem, however, is that

many patients with very early synovitis, when followed up, turn out to have

self-limiting disease, " Raza tells rheumawire. " The ability to predict, at a

very early stage, which patients with synovitis will develop RA is

important, as it will allow clinical studies of aggressive therapy to

determine whether it is possible to switch the rheumatoid disease process

off during this early phase. "

Anti-CCP adds to predictive value of RF

The first part of this work was a cross-sectional study to validate the

anti-CCP antibody assay and to confirm the reported sensitivities and

specificities of the anti-CCP antibody test. Anti-CCP was then assessed in

96 patients with very early synovitis (<3 months), who were subsequently

followed for up to 18 months (median 78 weeks).

In the validation study, anti-CCP was positive in 86% of patients with

established RF-positive RA and in 25% of patients with established

RF-negative RA. " The specificity of anti-CCP for a diagnosis of RA was 96%;

the sensitivity was 57%. Reducing the cutoff for assay seropositivity to 5

IU/mL reduced specificity to 95% and improved sensitivity to 62%.

The second part of the study was the testing and follow-up of patients with

very early inflammatory arthritis. Of the patients, 24 (25%) met American

Rheumatism Association (ARA) criteria for RA at some point. Of those, 19 had

persistent disease and 5 had disease that resolved during follow-up. The

investigators examined several possible predictive factors and found that

the combination of seropositivity for RF and anti-CCP antibodies had the

highest specificity (97%) and positive predictive value (PPV) (86%) for

predicting the development of persistent RA, with a sensitivity of 63% and a

negative predictive value of 91%.

" This combination of autoantibodies is apparent in some patients with other

established inflammatory diseases. However, in patients with very early

synovitis it can be used with high specificity and PPV to identify those

destined to develop RA who may be appropriate for very early intervention, "

the researchers write.

Combination may improve patient selection for clinical trials

" In my opinion, the data suggest that we need to conduct clinical studies of

early aggressive therapy in patients who are seropositive for rheumatoid

factor and anti-CCP antibody (before these patients necessarily fulfill

current formal classification criteria for RA), " Raza says.

Although anti-CCP antibody adds to the specificity of RF, Raza emphasizes

that the combination requires validation in larger populations of patients

with very early inflammatory arthritis to define more precisely the

additional benefit of anti-CCP antibody over RF alone. " The sensitivity of

this antibody combination was only 63%, and so, by no stretch of the

imagination, should it be regarded as a tool to exclude RA, " Raza adds.

Source

Raza K, Breese M, Nightingale P, et al. Predictive value

of antibodies to cyclic citrullinated peptide in patients with very early

inflammatory arthritis. J Rheumatol 2005; 32:231-238.

I'll tell you where to go!

Mayo Clinic in Rochester

http://www.mayoclinic.org/rochester

s Hopkins Medicine

http://www.hopkinsmedicine.org