OBJECTIVES: A recently published claims-based algorithm to evaluate effectiveness of biologics for rheumatoid arthritis (RA) was validated using data from the Veteran Health Administration and VA RA registry. The objective was to compare 1-year cost per responder among biologics approved for first-line treatment of moderate to severe RA, etanercept, adalimumab, infliximab, golimumab, and abatacept among patients in a US health plan using this claims-based algorithm. METHODS: This retrospective cohort study used commercial claims data from the Optum Research Database, including medical and pharmacy claims for >13.3 million individuals.  Adult patients with RA (ICD-9 714.0x) newly initiating biologic treatment between Jan 1, 2008 and Dec 1, 2010 followed by ≥12 months of continuous enrollment were included. Patients with other diagnoses for which these agents are approved were excluded. The algorithm classifies a drug as “non-effective” if any of the following criteria are met: low adherence MPR < 80% or receiving less than the expected number of infusions/injections; increase in biologic dose or frequency; switching biologics; adding new non-biologic Diseases Modifying Anti-Rheumatic Drugs; new glucocorticoid use or increase in glucocorticoid dose; and > 1 parenteral or intra-articular glucocorticoid injection. Drug costs were estimated using actual medication usage and administration costs. Non-responders were defined as patients in whom the drug was classified as “non-effective”. RESULTS: A total of 5,474 patients (2,425 etanercept, 1,857 adalimumab, 773 infliximab, 295 abatacept, and 124 golimumab) were included. Across agents, between 76% and 85% were female, with a mean age of 48 years. The medications were classified “effective” (low disease activity or remission) in 32.7%, 27.7%, 19.0%, 30.2%, and 32.3% of patients respectively. Mean cost per responder was lowest for etanercept ($43,935), followed by golimumab ($49,589), adalimumab ($52,752), abatacept ($62,300), and infliximab ($101,402). CONCLUSIONS: Etanercept had the lowest cost per responder in RA using a new, validated claims based algorithm.