OBJECTIVES: To assess the cost-effectiveness of flexible dosing with etanercept compared with adalimumab or infliximab treatment in patients with moderate to severe psoriasis. METHODS: An economic model was constructed to estimate the incremental cost per quality adjusted life year for each therapy compared with no systemic therapy (NST). Patients met UK criteria for biologic treatment, which require both a Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) >=10 at baseline. Initial response rates were taken from registration studies for each agent: quality of life gain associated with response from patient level data in etanercept studies. Adalimumab and infliximab were given continuously in line with product licenses. Etancercept can be used flexibly, with some patients experiencing drug free intervals between courses of therapy: UK observational data found that 64% of etanercept users experience such intervals, with the remainder having continuous therapy.  Response and withdrawal rates were taken from clinical studies, and extrapolated to a time horizon of 10 years. Costs were estimated from a UK payer perspective including drugs, administration visits and hospital stay for treatment failures. Stochastic analysis was undertaken to quantify uncertainty. RESULTS: The model estimated incremental cost-effectiveness ratios (ICER) of each therapy compared with NST to be: £12,600 (95% CI: £10,131, 14,066) for etanercept flexible dosing; £17,975 (£17,779, 31,106) for continuous adalimumab and £44,377 (£44,038, 73,815) for continuous infliximab. The ICER for etanercept therapy was sensitive to the frequency and duration of drug free intervals in these patients but was below the ICER for continuous therapies. CONCLUSIONS: The model found flexible dosing with etanercept to be more cost-effective than continuous therapy, as it allows control to be maintained at lower drug cost. This finding is consistent with a previous publication (Sitzo 2008), but has now been confirmed with drug utilisation data from UK practice.