A Cost-Effectiveness Analysis of Alternative Disease Management Strategies in Patients with Crohn's Disease Treated with Azathioprine or 6-Mercaptopurine

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Abstract
Azathioprine (AZA) is effective for the maintenance of a steroid free remission in Crohn's disease (CD). Thiopurine methyltransferase (TPMT) is important for the metabolism of AZA and influences the production of active AZA metabolites. AZA dose selection based on pharmacogenetic testing of TPMT and metabolite monitoring (MM) may offer a safety and efficacy advantage over traditional dosing strategies. We performed a decision analysis to estimate the potential costs and effectiveness of TPMT screening and MM as disease management strategies for CD. Strategies applying TPMT and/or MM to influence treatment decisions were compared to community care (CC). The impact on toxicity minimization and improved time to initial and sustained response was evaluated. A 1-yr model was developed from the third-party payer perspective for mild to moderately chronically active, steroid-treated CD patients. Effectiveness and toxicity defined by time to response CD activity index (CDAI <150, +/- steroids) or time to sustained response (CDAI <150, off steroids x 8 wk) and reduction in leukopenic events, respectively. One- and two-way sensitivity analyses were conducted to determine the effect of varying individual estimates from those used in the base-case analysis. MM, TPMT, and TPMT + MM strategies as compared to CC achieved an earlier time to initial response (18.66, 18.96, and 19.10 vs. 22.41 wk, respectively) and sustained response (39.83, 42.91, and 39.8 vs. 45.36 wk, respectively). The least costly strategy at 1 yr was TPMT ($3,861) and the most costly strategy was CC ($7,142). Each alternative strategy was shown to dominate CC (i.e., less costs and faster time to response or sustained response). The cost-effectiveness rankings were robust to sensitivity analyses on key variables. The addition of alternative strategies to CC may improve AZA outcomes and reduce the total cost of care for steroid treated chronically active CD patients, with TPMT being more beneficial for initial response to treatment and MM being more beneficial for sustained response to treatment.