Cost-Effectiveness of Eltrombopag Plus Immunosuppressive Therapy Versus Immunosuppressive Therapy Alone in Adults with Severe Aplastic Anemia in the United States
Authors: Potnis Kunal C , Ito Satoko , Patel Kishan , Shallis Rory M. , Podoltsev Nikolai A. , Kewan Tariq , Stempel Jessica M. , Mendez Lourdes , Huntington Scott F , Stahl Maximilian , Zeidan Amer M. , Bewersdorf Jan Philipp , Goshua George 
Published: December 2024

Introduction:
Eltrombopag, an oral thrombopoietin receptor agonist, emerged as an efficacious treatment in conjunction with traditional immunosuppressive therapy (IST; consisting of horse antithymocyte globulin [ATG] and cyclosporine) for the treatment of severe aplastic anemia in the randomized phase III RACE trial (N Engl J Med 2022;386:11-23). Specifically, patients treated with eltrombopag and IST achieved a 68% overall response rate at 6 months, compared to 44% in patients treated with IST alone. These results corroborated an earlier NIH phase I/II trial that led to U.S. FDA approval of eltrombopag for first-line treatment of severe aplastic anemia in 2018. However, eltrombopag can pose a significant cost burden at ~$157,000 for a 6-month course. We performed the first cost-effectiveness analysis of eltrombopag plus IST versus IST alone in adults with newly diagnosed severe aplastic anemia.
Methods:
We developed a Markov model based upon demographic data and probabilities of remission, relapse, retreatment/initiation of later-line therapies, and development of adverse events from the RACE trial. Patients newly diagnosed with severe aplastic anemia who were ineligible for hematopoietic stem cell transplantation (with a median age of 53 years) entered the model and received either first-line IST alone (4 days of ATG and at least 12 months of cyclosporine) or IST along with eltromobopag (3-to-6-month course depending on response at 3 months). Oral drug costs were based upon a discounted average wholesale price. Inpatient costs were based upon the Medicare inpatient prospective payment system, and remaining costs were based upon previously published literature. All costs were converted to 2024 U.S. dollars using the general consumer price index. Effectiveness was measured in quality-adjusted life years (QALYs). Utility values were derived from quality-of-life data collected in the RACE trial. The primary outcome was the incremental net monetary benefit (iNMB) in U.S. dollars for eltrombopag plus IST versus IST alone. We used a 3% discount rate, a lifetime time horizon, and a U.S. payer perspective. We conducted one-way deterministic sensitivity analyses to assess the impact of varying each parameter by +/- 20% on the model's results. We also conducted a probabilistic sensitivity analysis to assess uncertainty in all input parameters simultaneously across 10,000 Monte Carlo iterations, where beta-PERT distributions were used for probabilities and utilities and gamma distributions were used for costs. The difference method was utilized for ordered utilities.
Results:
In our base-case analysis, the eltrombopag plus IST strategy versus IST alone strategy incurred lifetime costs of $507,000 and $401,000 and accrued 13.87 QALYs and 13.68 QALYs, respectively, resulting in a per-patient iNMB of $77,000 [95% credible interval -$7,000 - $183,000] in favor of IST alone. Deterministic sensitivity analyses demonstrated that our model was most sensitive to the probability of receiving second-line eltrombopag in the IST alone arm; notably, 84% of patients in the IST alone arm in the RACE trial who received second-line therapy received eltrombopag. On probabilistic sensitivity analysis, the IST alone strategy was favored in 99%, 97%, and 94% of iterations at willingness to pay thresholds of $50,000, $100,000, and $150,000/QALY, respectively.
Conclusions:
At current pricing, eltrombopag plus IST is unlikely to be a cost-effective therapeutic strategy in adults with severe aplastic anemia in the United States. Longer-term follow-up data can help better clarify the cost-effectiveness of this strategy in adults with untreated severe aplastic anemia.