A Canadian Cost-Effectiveness Analysis for the Treatment of Immune Thrombocytopenia: Assessing the Relative Value of with Eltrombopag Versus Romiplostim

Background:

Eltrombopag (EPAG) was evaluated as a second line treatment for adult chronic immune thrombocytopenia (ITP) in the 2005 Phase III RAISE randomized, placebo-controlled trial. More than 80% of patients reached satisfactory platelet counts within two weeks. However, the relative value of EPAG as a second line treatment for ITP remains to be formally assessed.

Objective:

This study aimed to estimate the cost-effectiveness of treating ITP with comparable thrombopoietin receptor agonists: EPAG versus Romiplostim (ROMI).

Methods:

A cost-effectiveness model was developed from a Canadian payer perspective. In the base case, Markov model was implemented to estimate the benefits and costs expected with each treatment over a lifetime time horizon. Three health states based on the clinical pathway and current guidelines for the treatment of ITP were included in the model: (1) on treatment, (2) treatment failure/discontinuation, and (3) mortality. As reducing bleeding is the therapeutic goal in ITP, bleeding rates were incorporated into the model. Pre-mortality, patients could experience three events: no bleeding, mild/moderate bleeding, or severe bleeding. Data on EPAG use were obtained from the EXTEND study, an open-label extension of four trials including RAISE. For ROMI, data were obtained from Phase III trials and a subsequent extension study. Lifetime overall survival was extrapolated by applying constant treatment-specific mortality rates derived from severe bleeding events and natural mortality rates. As no health-related quality of life data were collected during the RAISE clinical trial, EPAG health state utilities were obtained from other relevant studies (Szende, 2010; Leontiadis, 2010; ROM NICE submission TA221). The costs of drugs (primary and secondary therapy), rescue medications, routine care, bleeding episodes, adverse events, and mortality were incorporated into the model. Costs, in Canadian dollars, were derived from the relevant pricing databases. Costs and benefits were discounted at 1.5% per year according to CADTH guidelines.

Results:

EPAG-treated patients gained 22.53 life years (LY) and 18.81 quality-adjusted life years (QALY) while those treated with ROMI gained 22.45 LYs and 18.80 QALYs. The total cost for EPAG treatment was estimated at $513,301 versus $805,025 for ROMI treatment. EPAG was dominant (lower cost, greater benefit) in terms of both costs per LY and costs per QALY. Sensitivity analyses supported base case findings. Deterministic sensitivity analysis predicted the greatest sensitivity to variations in the rates of severe bleeding, discontinuation, and natural mortality. The probabilistic sensitivity analysis demonstrated the probability of cost-effectiveness was 55.7% at both $25,000 and $50,000 thresholds and EPAG was therefore a reasonably efficient use of resources. In a subsequent cost-consequence analysis, EPAG patients experienced fewer severe bleeding events (0.05 versus 0.08 for ROMI) and, overall, their annual costs were lower ($65,514 versus $96,914 for ROMI).

Conclusion:

Both EPAG and ROMI has demonstrated significant improved in bleeding versus the standard of care in the phase 3 clinical trial.s These results were applied in the economic analysis and EPAG proved to be more cost-effective as compared to ROMI.