OBJECTIVES: Clinical studies indicate switching to a second biologic or combination therapy with an immunosuppressant after failure of first biologic can be effective in patients with moderate to severe plaque psoriasis not responding to the first biologic. METHODS: A systematic literature review was performed to assess treatment pathways included in cost-effectiveness (CE) estimates of biologic treatments of moderate to severe psoriasis and compare these pathways with those recommended in psoriasis treatment guidelines.  RESULTS: Twenty-one CE modeling studies were identified. Of these 10 estimated incremental cost per responder for >=1 biologics over time horizons varying from 12 weeks to 18 months. Treatment pathways were considered not relevant in these studies. In 11 studies with time horizons up to 10 years where treatment pathways were considered, 5 studies included a switch to non-systemic therapy or best supportive care after failure of the initial biologic. In 6 of  11 studies, failure of the initial biologic was followed by monotherapy with a second-line biologic - one of the recommendations in current treatment guidelines. In only 1 of 6 studies that considered treatment sequencing was the efficacy of the second-line biologic adjusted downwards compared to first line treatment. None of the cost-effectiveness analyses included dose titration with the first-line biologic or combination therapy with a biologic plus methotrexate or phototherapy after failure of the first-line biologic as recommended in some treatment guidelines.  CONCLUSIONS: In most long term CE studies, failure of the first biologic was followed by biologic monotherapy of the second, without efficacy adjustment. Some treatment guidelines support dose titration or combination treatment after failure of a first-line biologic. Nevertheless, these options were not included in the published CE models with time horizons up to 10 years. For decision makers there may be a need for more extensive models where such strategies are allowed.