OBJECTIVES: To evaluate the cost-utility and budget impact (BI) of certolizumab pegol (CZP) as an add-on therapy to methotrexate (MTX) versus other first line biological DMARDs, in the treatment of adult patients with active RA who did not respond adequately to DMARDs, including MTX, in Greece. METHODS: A Markov (cohort health state transition) model was developed to evaluate the cost-utility of CZP versus other TNF-α inhibitors recommended in Greece (etanercept [ETA], adalimumab [ADA] and infliximab [IFX]). Treatment efficacy was measured using the ACR-responses (ACR20/50/70) at 6 months. ACR estimated rates were based on adjusted indirect comparison (MTX as common comparator) of published clinical trials. Utilities were derived from EQ-5D data from CZP RA clinical trials. Clinical history/resource use data came from published literature. Sensitivity analyses were conducted. The BI of CZP as an add-on therapy to MTX was estimated from payer perspective over 2011–2015. The alternatives to CZP include all TNF-α inhibitors recommended in Greece (etanercept, adalimumab, infliximab, golimumab). Epidemiological data were used to estimate the RA population eligible for CZP therapy. Published 2011 hospital unit costs (drug acquisition, administration, monitoring, resources) in both analyses were taken from Greek routine sources/expert opinion. Base case analysis assumed a payer perspective, costs discounted at 3.5% (CU/BI), a lifetime horizon, with outcomes discounted at 3.5% (CU), 75kg patient-fixed average weight (BI). RESULTS: Base case analysis indicated that CZP is cost-effective compared with all combination therapies considered (at €60,000(3xGDP/capita) willingness-to-pay threshold), with an incremental cost-effectiveness ratio of €19,181/QALYs, €32,208/QALYs, €22,349/QALYs versus ADA+MTX, ETA+MTX and IFX+MTX, respectively. In terms of BI, the introduction of CZP on the Greek market produced cumulative net savings of €7.68M during 2011–2015. CONCLUSIONS: This analysis shows that CZP+MTX is cost-effective versus. the other TNF-α inhibitors recommended in Greece for the treatment of RA and its use is anticipated to result in budgetary net savings.