OBJECTIVES: In 2012, NICE initiated a multiple treatment assessment reviewing all licensed biologics for the treatment of rheumatoid arthritis (RA) previously treated with conventional DMARDs only. The sequence of treatments used after the failure of first biologic treatment was to be included as part of the cost-effectiveness modelling. We therefore built a model to match the treatment pathway for first-line biologics and beyond. METHODS: We researched the treatment pathway and existing cost-effectiveness models in order to create an appropriate model. We rebuilt the model used by the technology assessment group in TA195, which considered second-line biologics and beyond. We adapted this model to reflect the current treatment pathway and consider first line biologics. RESULTS: We created a patient simulation model, which generated a cohort of virtual patients and tracked their costs and QALYs over the pathway. Patients began treatment with a biologic, and could discontinue at month 6 due to an adverse event (AE), in which case they switched to a different biologic, with first-line efficacy. Patients who did not have an AE discontinued at month 6 if their DAS 28 improvement was insufficient. After discontinuation at month 6, or later, patients next received rituximab, unless contraindicated. If rituximab was contraindicated, or the patient had an AE by month 6, they moved onto another biologic treatment, after which they received a DMARD treatment sequence (including palliative care). Patients who had insufficient DAS28 response on rituximab at month 6 switched to tocilizumab (unless received previously), after which they received the DMARD sequence. Patients who had sufficient DAS28 improvement with rituximab remained on rituximab long-term, until they received the DMARD treatment sequence. Patients could exit the model at any point if they died. CONCLUSIONS: We used robust methodology and clinical rationale to assess the cost-effectiveness of licenced treatments reflected across NICE’s recommended treatment pathway for RA.