Background/Purpose:   Biological markers are objective molecular indicators possessing diagnostic, prognostic and predictive utility. The detection of antibodies to cyclic citrullinated peptides (Anti-CCP) may occur long before the onset of rheumatoid arthritis (RA) symptoms. A positive test is associated with severe erosive disease and can predict disease progression. Diagnostic accuracy is crucial for clinicians to initiate a more aggressive treatment plan early in the course of the disease. Objective of study: to compare diagnostic accuracy of anti-CCP tests from different manufacturers for RA diagnosis.

Methods:   A rigorous systematic literature review identified studies from 2004-2015. Pooled estimates for sensitivity, specificity, positive likelihood ratio (LR+), negative LR (LR-) were calculated by random effects meta-regression. Covariates influence was analyzed in sub-analyses (RA-type and control type).

Results:   Out of 3100 papers, 88 met the inclusion criteria reporting the diagnostic accuracy of CCP tests from 7 manufacturers, and including 22 studies from early RA patients (< 2 years), 9 studies from established RA patients (> 2 years), while 20 studies used serum samples from a mixed population of RA patients (combination of early and established). Forty seven studies obtained control serum samples from diseased patients, 12 studies from healthy individuals, 28 studies from a mixed control populations and 5 studied defined the control group as non-RA. The included studies presented data from 34 countries worldwide. The Disease Activity Score in 28 joints (DAS28) was used to assess the severity of disease in rheumatoid arthritis (RA) patients in 17 studies (20.2%). Sensitivity ranged between 65.6-83.1%; specificity between 87.6-96.4%; LR+: 6.5-19; LR-: 0.2-0.4. Overall, the diagnostic performance of EuroImmune/Anti-CCP ELISA, ThermoFisher/EliA and Inova Diagnostics/Quanta Flash distinguished from the others by having high sensitivities, and the highest specificities and positive LRs. This result did not seem to be influenced by the investigated covariates. The single-gate analysis showed that the ThermoFisher/EliA CCP test sensitivity remained stable compared to the overall analysis; in particular, it had significantly better sensitivity than the both the Inova Diagnostics/Quanta Lite 3.0 test and the Euro-diagnostica/Immunoscan test. There was a non-significant trend in favor of the Roche/Elecsys test, however none of the comparator index tests were shown to have significantly better sensitivity than the ThermoFisher/EliA CCP test.

Conclusion:   By maximizing LR+ and minimizing false negatives, accurate RA diagnosis is possible, allowing for timely appropriate treatment strategy. Results show: 1) EuroImmune/Anti-CCP ELISA, ThermoFisher/EliA and Inova Diagnostics/Quanta Flash generally have better diagnostic performance; 2) ThermoFisher/EliA and Roche/Elecsys appear as the best tests for diagnosing suspected RA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/precision-medicine-in-rheumatoid-arthritis-systematic-literature-review-and-meta-analysis-on-the-diagnostic-accuracy-of-anti-ccp-tests-for-the-diagnosis-of-rheumatoid-arthritis/