OBJECTIVES: Administrative claims contain detailed medication, diagnosis, and procedure data, but their lack of clinical outcomes for rheumatoid arthritis (RA) has limited their use in comparative effectiveness research.  A validated claims-based algorithm uses adherence, dosing, and treatment modifications to estimate biologics’ effectiveness (low disease or remission)  for RA. The objective was to implement this algorithm in a US managed-care database and calculate the cost per algorithm-defined responder among biologics approved for moderate to severe RA (etanercept, adalimumab, infliximab, golimumab, abatacept). METHODS: Data were obtained from the IMS PharMetrics Plus™ Database, comprised of adjudicated medical and pharmaceutical claims for 150 million unique enrollees. The cohort included patients with RA aged 18-63, initiating treatment between January 2007 and December 2010, without RA biologics 6 months before first treatment, and enrolled between 6 months before and 12 months after first biologic. Other TNF responsive conditions were excluded. The algorithm defines lack of effectiveness as: medication possession ratio < 80% (or fewer infusions/injections than specified on US label), increase in biologic dose or frequency interval, switching biologics, adding new non-biologic Disease Modifying Anti-Rheumatic Drugs, glucocorticoid use, initiation or increase of glucocorticoid dose, or > 1 parenteral or intra-articular injection during the follow-up period. Drug and administration costs were obtained from allowed amounts on claims. RESULTS: The cohort included 16,011 patients, mean age 49.3, 76.7% female. Algorithm effectiveness (low disease or remission) criteria were met in 31.0% of etanercept (n=7,247), 28.6% of  adalimumab (n=4,991), 20.2% of infliximab (n=2,352), 28.6% of abatacept (n=1,160), and 27.2% of golimumab (n=261) patients in the first 12 months of treatment. Mean first year cost per responder was lowest for etanercept ($50,141), followed by golimumab ($53,386), adalimumab ($56,941), abatacept ($73,516), and infliximab ($114,089). CONCLUSIONS: Etanercept had the highest estimated effectiveness and lowest cost per responder among first-line RA biologics using a new, validated claims-based algorithm.