Background/Purpose:  The new 2012 ACR guidelines for the management of gout have provided updated recommendations; however, the employed method do not address the societal costs of the recommendations.  We evaluated the cost-effectiveness of 5 first-line urate-lowering therapy (ULT) strategies (incorporating dose-escalation reflective of real practice) for the management of gout over a lifetime.

Methods :  We developed a Markov model to calculate lifetime health benefits, costs, and incremental cost-effectiveness ratios (ICERs) of 5 ULT strategies: 1) no ULT, 2&3) allopurinol and febuxostat used as single therapy options, 4) allopurinol-febuxostat sequential therapy, and 5) febuxostat-allopurinol sequential therapy.  We investigated two ULT dosing scenarios: 1) fixed dosing (febuxostat[80 mg daily]  ; allopurinol [300 mg daily]), 2) dose escalation  (febuxostat [up to 120mg daily]; allopurinol [up to 800mg daily]). The fixed dosing scenario is reflective of recent randomized trials, whereas the dose-escalation scenario is reflective of real practice. Health states in the model reflected those that could occur during a gout patient’s lifetime: controlled (serum urate acid (SUA) <6.0 mg/dl), or uncontrolled (SUA ³ 6.0 mg/dl). Within each state we accounted for gout flares and ULT associated adverse events, including allopurinol hypersensitivity syndrome.  Costs were evaluated from a payer perspective.  Cost and utility estimates were obtained from the literature and discounted by 3% per year. Gout flares and ULT associated adverse events were associated with a disutility.  Sensitivity analyses were conducted to evaluate the impact of parameter uncertainty.

Results :  In both dosing scenarios (fixed and escalating), allopurinol as a single-line option was the least costly option (discounted lifetime cost = $12,004 and $10,477, respectively) and was more effective than no ULT (Table).  In both dosing scenarios, allopurinol- febuxostat sequential therapy was more costly and more effective than allopurinol single therapy, with an ICER of $24,400/quality-adjusted life year (QALY) (fixed dosing) and $33,500/QALY (dose escalation).  In both dosing scenarios, febuxostat -allopurinol sequential therapy had a cost-effectiveness ratio >$300,000/QALY, and febuxostat single therapy cost more and was less effective than febuxostat -allopurinol sequential therapy (dominated) (Table). The allopurinol- febuxostat sequential therapy result in the dose escalation scenario was sensitive to the cost of febuxostat and time spent on a given ULT without control.  

Conclusion: Allopurinol single therapy is cost saving compared to no ULT.  Allopurinol-febuxostat sequential therapy appears to be cost-effective as compared with allopurinol single therapy.  Febuxostat single therapy and febuxostat-allopurinol sequential therapy are unlikely to be cost-effective.