BACKGROUND: Anticitrullinated protein antibodies (ACPAs) are serological 
biomarkers associated with early, rapidly progressing rheumatoid arthritis (RA), 
including more severe disease and joint damage. ACPA testing has become a 
routine tool for RA diagnosis and prognosis. Furthermore, treatment efficacy has 
been shown to vary by ACPA-positive status. However, it is not clear if the 
economic burden of patients with RA varies by ACPA status.
OBJECTIVE: To determine if the economic burden of RA varies by patient ACPA 
status.
METHODS: IMS PharMetrics Plus health insurance claims and electronic medical 
record (EMR) data from 2010-2015 were used to identify patients with incident 
RA. Patients were aged ≥ 18 years, had ≥ 1 inpatient or ≥ 2 outpatient claims 
reporting an RA diagnosis code (ICD-9-CM code 714.0), and had an anticyclic 
citrullinated peptide (anti-CCP; a surrogate of ACPA) antibody test within 6 
months of diagnosis. Incident patients were defined as those who had no claims 
with an RA diagnosis code in the 6 months before the first observed RA 
diagnosis. The primary outcome of interest was RA-related medical expenditures, 
defined as the sum of payer- and patient-paid amounts for all claims with an RA 
diagnosis code. Secondary outcomes included health care utilization metrics such 
as treatment with a disease-modifying antirheumatic drug (DMARD) and physician 
visits. Generalized linear regression models were used for each outcome, 
controlling for ACPA-positive status (defined as anti-CCP ≥ 20 AU/mL), age, sex, 
and Charlson Comorbidity Index score as explanatory variables.
RESULTS: Of 647,171 patients diagnosed with RA, 89,296 were incident cases, and 
47% (n = 42,285) had an anti-CCP test. After restricting this sample to patients 
with a linked EMR and reported anti-CCP test result, 859 remained, with 24.7% (n 
= 212) being ACPA-positive. Compared with ACPA-negative patients, adjusted 
results showed that ACPA-positive patients were more likely to use either 
conventional (71.2% vs. 49.6%; P < 0.001) or biologic (20.3% vs. 11.8%; P < 
0.001) DMARDs during the first year after diagnosis and had more physician 
visits (5.58 vs. 3.91 times per year; P < 0.001). Annual RA-associated total 
expenditures were $7,941 for ACPA-positive and $5,243 for ACPA-negative patients 
(Δ = $2,698; P = 0.002). RA-associated medical expenditures were $4,380 for 
ACPA-positive and $3,427 for ACPA-negative patients (Δ = $954; P = 0.168), 
whereas DMARD expenditures were $3,560 and $1,817, respectively (Δ = $1,743; P = 
0.001).
CONCLUSIONS: RA-related economic burden is higher for patients who are 
ACPA-positive compared with those who are ACPA-negative. Providers may wish to 
inform patients diagnosed with ACPA-positive RA about the likely future disease 
and economic burden in hopes that both stakeholders can be more proactive in 
addressing them.
DISCLOSURES: Funding for this research was contributed by Bristol-Myers Squibb. 
Patel and Price are employees and stockholders of Bristol-Myers Squibb. Shafrin 
and Tebeka are employees of Precision Health Economics, a health care consulting 
firm that received funding from Bristol-Myers Squibb to conduct this study. 
Michaud has received a grant from Pfizer and is employed by the National Data 
Bank for Rheumatic Diseases, which has received funds from Amgen, Bristol-Myers 
Squibb, Eli Lilly, Janssen, Pfizer, and Regeneron. Study concept and design were 
contributed by Shafrin, Price, Patel, and Michaud. Shafrin, Price, and Patel 
collected the data, and all authors contributed equally to data analysis. The 
manuscript was written by Shafrin and Tebeka and revised by Shafrin, Price, 
Patel, and Michaud.