TY - JOUR

T1 - Impact of non-adherence and flare resolution on the cost effectiveness of treatments for gout

T2 - Application of a linked pharmacometric/pharmacoeconomic model

AU - Hill-McManus, Daniel

AU - Marshall, Scott

AU - Soto, Elena

AU - Lane, Steven

AU - Hughes, Dyfrig

N1 - MRC Network of Hubs for Trial Methodological Research (HTMR), reference number MR/L004933/1- Q25, and the MRC North-West HTMR, reference number MR/K025635/1 We acknowledge the support of the Supercomputing Wales project, which is part-funded by the European Union's Convergence European Regional Development Fund, administered by the Welsh Government

PY - 2018/12

Y1 - 2018/12

N2 - BackgroundDual urate-lowering therapy (ULT) with lesinurad in combination with either allopurinol or febuxostat is an option for patients with gout unsuccessfully treated on either monotherapy. Treatment failure is often a result of poor medication adherence. Imperfect adherence in clinical trials may lead to biased estimates of treatment effect and confound the results of cost-effectiveness analyses.ObjectivesTo estimate the impact of varying medication adherence on the cost effectiveness of lesinurad dual therapy and estimate the value-based price of lesinurad at which the incremental cost-effectiveness ratio is equal to £20,000 per quality-adjusted life-year (QALY).MethodsTreatment effect was simulated using published pharmacokinetic-pharmacodynamic models and scenarios representing adherence in clinical trials, routine practice, and perfect use. The subsequent cost and health impacts, over the lifetime of a patient cohort, were estimated using a bespoke pharmacoeconomic model.ResultsThe base-case incremental cost-effectiveness ratios comparing lesinurad dual ULT with monotherapy ranged from £39,184 to £78,350/QALY gained using allopurinol and £31,901 to £124,212/QALY gained using febuxostat, depending on the assumed medication adherence. Results assuming perfect medication adherence imply a per-quarter value-based price of lesinurad of £45.14 when used in dual ULT compared with allopurinol alone and £57.75 compared with febuxostat alone, falling to £25.41 and £3.49, respectively, in simulations of worsening medication adherence.ConclusionsThe estimated value-based prices of lesinurad only exceeded that which has been proposed in the United Kingdom when assuming both perfect drug adherence and the eradication of gout flares in sustained treatment responders.

AB - BackgroundDual urate-lowering therapy (ULT) with lesinurad in combination with either allopurinol or febuxostat is an option for patients with gout unsuccessfully treated on either monotherapy. Treatment failure is often a result of poor medication adherence. Imperfect adherence in clinical trials may lead to biased estimates of treatment effect and confound the results of cost-effectiveness analyses.ObjectivesTo estimate the impact of varying medication adherence on the cost effectiveness of lesinurad dual therapy and estimate the value-based price of lesinurad at which the incremental cost-effectiveness ratio is equal to £20,000 per quality-adjusted life-year (QALY).MethodsTreatment effect was simulated using published pharmacokinetic-pharmacodynamic models and scenarios representing adherence in clinical trials, routine practice, and perfect use. The subsequent cost and health impacts, over the lifetime of a patient cohort, were estimated using a bespoke pharmacoeconomic model.ResultsThe base-case incremental cost-effectiveness ratios comparing lesinurad dual ULT with monotherapy ranged from £39,184 to £78,350/QALY gained using allopurinol and £31,901 to £124,212/QALY gained using febuxostat, depending on the assumed medication adherence. Results assuming perfect medication adherence imply a per-quarter value-based price of lesinurad of £45.14 when used in dual ULT compared with allopurinol alone and £57.75 compared with febuxostat alone, falling to £25.41 and £3.49, respectively, in simulations of worsening medication adherence.ConclusionsThe estimated value-based prices of lesinurad only exceeded that which has been proposed in the United Kingdom when assuming both perfect drug adherence and the eradication of gout flares in sustained treatment responders.

M3 - Article

VL - 21

SP - 1373

EP - 1381

JO - Value in Health

JF - Value in Health

SN - 1524-4733

IS - 12

ER -