Cost-effectiveness of ipilimumab versus high-dose interferon as an adjuvant therapy in resected high-risk melanoma

Abstract

Background: Adjuvant ipilimumab was found to improve the overall survival and reduce toxicity compared to high-dose interferon (HDI) in patients with resected, high-risk melanoma. However, the cost of ipilimumab is substantially higher than HDI. This study evaluates the cost-effectiveness of ipilimumab as an adjuvant treatment in melanoma from a healthcare perspective.

Methods: We designed a Markov model simulating resected, high-risk melanoma patients receiving either ipilimumab or HDI. Transition probabilities, including risks of survival, disease progression, and toxicity, were ascertained from clinical trial data. Costs and quality of life measurements (health utilities) were extracted from the literature. Incremental cost-effectiveness ratios (ICERs), defined as incremental costs divided by incremental quality-adjusted life-years (QALYs), assessed cost-effectiveness. ICERs <$100,000/QALY were deemed cost-effective. We measured model uncertainty with one-way and probabilistic sensitivity analyses.

Results: In our base case model, ipilimumab increased costs by $107,100 and increased effectiveness by 0.43 QALY, yielding an ICER of $392,600/QALY. Our model was moderately sensitive to the costs of ipilimumab, though the cost of ipilimumab would need to decrease by 44% for ipilimumab to become cost-effective compared to HDI. The model was not sensitive to survival, toxicity, or other costs. Probabilistic sensitivity analysis showed that HDI would remain the cost-effective treatment option 96.2% of the time at a willingness-to-pay threshold of $100,000/QALY.

Conclusions: Adjuvant ipilimumab increases the survival and decreases the toxicity compared to HDI in resected, high-risk melanoma patients, though this would not be considered cost-effective due to the high price of ipilimumab.

Keywords: cost-effectiveness; high-dose interferon; immunotherapy; ipilimumab; melanoma.

FIGURE 1

Transition state diagram. This figure shows the potential health states patients could experience in this analysis. Ovals represent distinct disease states and arrows represent potential transitions between different disease states. HDI, high‐dose interferon; Tx, treatment

FIGURE 2

Survival and toxicity validation. This figure shows the cost‐effectiveness model validation results. The top panel shows how our model predicts the overall survival compared with the E1609 trial. The bottom panel shows how our model predicts the overall survival, relapse‐free survival, grade 3–4 toxicity, and grade 5 toxicity compared with the E1609 trial

FIGURE 3

One‐way sensitivity analyses. These graphs represent the cost‐effectiveness of ipilimumab compared to HDI, measured by incremental cost‐effectiveness ratios (ICERs). The horizontal dashed line represents the willingness‐to‐pay threshold, which is set at $100,000/QALY, and the region below the dashed line represents ICERs at which ipilimumab would be considered cost‐effective compared to HDI. Panel A illustrates how the ICER changes with varying costs of ipilimumab per infusion. Panel B demonstrates how the ICER varies with the hazard ratio of death for ipilimumab compared to HDI. Panel C demonstrates how the ICER varies with model time horizon. HDI, high‐dose interferon; HR, hazard ratio; QALY, quality‐adjusted life‐year

FIGURE 4

Probabilistic sensitivity analysis. This plot shows the results of a probabilistic sensitivity analysis comparing the cost‐effectiveness of ipilimumab with HDI for resected, high‐risk melanoma. The dashed line represents a wiliness‐to‐pay threshold of $100,000/QALY. HDI, high‐dose interferon; QALY, quality‐adjusted life‐year

FIGURE 5

Probabilistic sensitivity analysis scatter plot. This plot shows the distribution of incremental costs and incremental effectiveness of individual iterations of the probabilistic sensitivity analysis comparing the cost‐effectiveness of ipilimumab versus HDI. The dashed lines represent willingness‐to‐pay thresholds of $100,000/QALY, $200,000/QALY, and $500,000/QALY (see figure legend). Points on the graph represent individual iterations of the probabilistic sensitivity analysis. Points to the right of each dashed line indicate iterations in which ipilimumab was cost‐effective compared with HDI at that specific willingness‐to‐pay threshold; points to the left of each dashed line indicate iterations in which ipilimumab was cost‐ineffective compared to HDI at that specific willingness‐to‐pay threshold. WTP, willingness‐to‐pay, QALY, quality‐adjusted life‐year