Serum Autoantibody Multi-Analyte Testing in Rheumatoid Arthritis Can Reduce Avoidable Costs Associated from False Positive Results. A Simulation Study in the United States of America

Barbara Mascialino¹, Sascha Swiniarski², Isabel Gehring², Maryam Poorafshar¹, Teresa Tarrant³

¹ Thermo Fisher Scientific, Uppsala, Sweden

² Thermo Fisher Scientific, Freiburg, Germany

³ Duke School of Medicine, Division of Rheumatology and Immunology, Durham, NC, USA

Background/Purpose: 

Rheumatoid arthritis (RA) diagnosis requires a combination of clinical, laboratory, and imaging investigations. In clinical practice, testing for both Rheumatoid Factor (RF) and cyclic citrullinated peptides (CCP) is considered beneficial; however, when interpreting laboratory test results together, the clinician advertently decides whether test sensitivity or specificity is preferable.  The individual patient characteristics with the presence of appropriate signs and symptoms help the health care practitioner assign diagnostic value to:

A) a singular “positive result or positivity to at least one test” increases overall sensitivity by minimizing the number of False Negative (FN) results at the expense of specificity, or

B)  “positivity of all the tests” increases overall specificity by minimizing the number of False Positives (FPs), but overall sensitivity is lower than that of any single test.

FP results can lead to incorrectly managed individuals, who undergo further investigations, and bring about extra costs until a correct diagnosis is made.

The first aim of the present study was to evaluate the diagnostic performance of RF IgA, RF IgM and CCP, used alone or in multi-analyte combinations, in distinguishing a true positive diagnosis from a FP RA diagnosis. The secondary goal focused on the economic consequences brought about by FP serology results in the USA.

Methods: 

Single-/multi-analyte testing diagnostic performance was assessed in 190 established RA patients and 197 controls. A 12-month Markov model simulated 10,000 RA-suspected individuals tested with mono-/multi-analyte testing. Costs came from the published literature [1].

Results:

Multi-analyte testing increased diagnostic accuracy, reduced the number of FP results, and allowed for important cost savings due to a reduction of clinical procedures and resource utilization (Table 1).

Conclusion:

Simultaneous multi-analyte testing can improve the diagnostic accuracy over testing for the individual RF IgA, RF IgM and CCP tests by helping to maximize sensitivity (when disease is defined as “positivity to at least one test”) as well as maximizing specificity (if “positivity to all tests” occurs). Double- and triple-positive serology combinations minimize the number of FPs, thus reducing avoidable costs. Simultaneous multi-analyte testing demonstrates superior value from the patient and payer perspective.

[1] Birnbaum H, et al. Curr Med Res Opinion 2010; 26 (1): 77–90.