OBJECTIVES: Rheumatoid arthritis (RA) is a chronic, inflammatory disorder leading to disability and reduced quality of life. Effective treatment with biologic disease-modifying antirheumatic drugs (bDMARDs) is a significant economic burden on the US healthcare system. This study evaluated the cost per response of abatacept relative to adalimumab in ACPA positive RA patients from the US payer perspective.  METHODS: The Abatacept versus Adalimumab Comparison in Biologic-Naive RA Subjects with Background Methotrexate (AMPLE) trial was a randomized head to head study comparing subcutaneous (SC) abatacept to adalimumab. Recent subgroup analyses showed improved efficacy for serum anti-citrullinated protein antibody (ACPA) positive patients with increasing efficacy across ACPA quartile levels. A decision tree was designed to compare the cost per response of abatacept and adalimumab in a cohort of 1,000 ACPA positive patients over a 2-year time horizon. Clinical inputs were based on AMPLE. Response was based on American College of Rheumatology (ACR)20/70/90 and the health assessment questionnaire disability index (HAQ-DI). Unit costs were based on wholesale acquisition prices and U.S. administrative claims data.   RESULTS: The cost per response in ACPA positive patients favors abatacept SC compared to adalimumab SC for ACR20 ($5,514 versus $5,619), ACR70 ($10,094 versus $11,237), ACR90 ($20,187 versus $36,002) and HAQ-DI ($6,134 versus $6,540). When evaluating across ACPA quartiles, cost per ACR90 response consistently favors abatacept SC (Q1:$21,466 versus $24,477; Q2:$16,960 versus $33,246; Q3:$19,831 versus $48,768; Q4:$22,674 versus $30,794) as does cost per HAQ-DI (Q1:$6,278 versus $6,895; Q2:$6,025 versus $6,173; Q3:$6,880 versus $7,191; Q4:$5,339 versus $5,976). In ACPA Q4 patients, abatacept SC is consistently favored across all outcomes.  CONCLUSIONS: The cost per responder favors abatacept SC in ACPA positive patients. Cost savings were greater when more stringent response criteria (ACR70/90) were applied and with increasing ACPA levels, as demonstrated by lower cost per response for abatacept compared to adalimumab.