Modelling the cost-effectiveness of combination therapy for early, rapidly progressing rheumatoid arthritis by simulating the reversible and irreversible effects of the disease

OBJECTIVE: To estimate the cost-effectiveness of adalimumab plus methotrexate (MTX) versus MTX monotherapy in early, aggressive rheumatoid arthritis (RA) when explicitly modelling short-term (reversible) and long-term (irreversible, ie, joint damage) disease activity and physical function. METHODS: A microsimulation model was developed to unify, in a single cost-effectiveness model, measures of reversible and irreversible disease activity and physical function based on data from the PREMIER trial. Short term, reversible disease activity was modelled using DAS28 variables, including swollen joint counts, tender joint counts, C reactive protein concentration and pain. The DAS28 variables were then used in a logistic regression to predict short-term American College of Rheumatology (ACR) responses, which informed treatment continuation and switches. Long term, irreversible, radiographically documented joint damage was modelled using modified Total Sharp Score (mTSS). The model then linked both short-term disease activity and mTSS to the Health Assessment Questionnaire score, which was used to calculate direct and indirect costs, and quality adjusted life-years (QALYs). RESULTS: When both reversible and irreversible effects of therapy were included, combination therapy was estimated to produce 6-month 50% ACR responses in 75% of patients versus 54% in MTX monotherapy. Compared to MTX monotherapy, combination therapy resulted in 2.68 and 3.04 discounted life years and QALYs gained, respectively. Combination therapy also resulted in a net increase in direct costs of £106 207 for a resulting incremental cost/QALY gain of £32 425. When indirect costs were included in the analysis, the ICER (incremental cost-effectiveness ratio) decreased to £27 238. Disregarding irreversible effects increased the incremental cost-effectiveness ratio to £78 809 (when only direct costs were included). CONCLUSIONS: Starting with adalimumab plus MTX combination therapy in early, aggressive RA is cost-effective when irreversible damage is adequately considered.