OBJECTIVES: Assess impact of high patient out-of-pocket expenditures (OOP) on adherence and persistence with biologics for treatment of RA. METHODS: An incidence cohort of RA patients with pharmacy claims for etanercept or adalimumab during 2002 - 2003 was selected from a database of insurance claims from self-insured employer health plans (N = 2311). Adherence was defined as the medication possession ratio (MPR), proportion of the 365 days follow-up covered by days supplied. Persistence was determined using a survival analysis of the likelihood of discontinuing therapy. Patient's OOP was measured in two ways: 1) patient's coinsurance and co-payments per week of therapy, and 2) proportion of the biologic medication's cost paid by patient. Multivariate linear regression models of MPR and proportional hazard models of persistence estimated the impact of cost, adjusting for insurance type and demographic and clinical variables. RESULTS: OOP expenditure averaged $8 per week (SD $14, range $0 to $127). Only a very small proportion of patients (3.9%) paid more than $50 per week. The mean (SD) MPR for all patients was 0.52 (0.31). Adherence significantly decreased with increased weekly OOP (Coeff -0.0035, P<0.0001) and when patients paid a higher proportion of therapy costs (Coeff -0.8890, P<0.0001). This translates into approximately one week of therapy lost for every $5.50 increase in weekly OOP. Adherence was lower for younger patients, women and those with more comorbidities. Patients whose weekly cost exceeded $50 were more likely to discontinue than patients with lower costs (HR 1.59, P<0.001). CONCLUSION: The majority of patients have very reasonable OOP for biologics. However, a small number of patients are burdened with high OOP costs. The adverse impact of high OOP on adherence and persistence needs to be considered when making decisions about increasing co-pays.