Cost Utility of Lifelong Immunoglobulin Replacement Therapy vs Hematopoietic Stem Cell Transplant to Treat Agammaglobulinemia

Abstract

Importance: Lifelong immunoglobulin replacement therapy (IRT) is standard-of-care treatment for congenital agammaglobulinemia but accrues high annual costs ($30 000-$90 000 per year) and decrements to quality of life over patients' life spans. Hematopoietic stem cell transplant (HSCT) offers an alternative 1-time therapy, but has high morbidity and mortality.

Objective: To evaluate the cost utility of IRT vs matched sibling donor (MSD) and matched unrelated donor (MUD) HSCT to treat patients with agammaglobulinemia in the US.

Design, setting, and participants: This economic evaluation used Markov analysis to model the base-case scenario of a patient aged 12 months with congenital agammaglobulinemia receiving lifelong IRT vs MSD or MUD HSCT. Costs, probabilities, and quality-of-life measures were derived from the literature. Microsimulations estimated premature deaths for each strategy in a virtual cohort. One-way sensitivity and probabilistic sensitivity analyses evaluated uncertainty around parameter estimates performed from a societal perspective over a 100-year time horizon. The threshold for cost-effective care was set at $100 000 per quality-adjusted life-year (QALY). This study was conducted from 2020 across a 100-year time horizon.

Exposures: Immunoglobulin replacement therapy vs MSD or MUD HSCT for treatment of congenital agammaglobulinemia.

Main outcomes and measures: The primary outcomes were incremental cost-effectiveness ratio (ICER) expressed in 2020 US dollars per QALY gained and premature deaths associated with each strategy.

Results: In this economic evaluation of patients with congenital agammaglobulinemia, lifelong IRT cost more than HSCT ($1 512 946 compared with $563 776 [MSD] and $637 036 [MUD]) and generated similar QALYs (20.61 vs 17.25 [MSD] and 17.18 [MUD]). Choosing IRT over MSD or MUD HSCT yielded ICERs of $282 166 per QALY gained over MSD and $255 633 per QALY gained over MUD HSCT, exceeding the US willingness-to-pay threshold of $100 000/QALY. However, IRT prevented at least 2488 premature deaths per 10 000 microsimulations compared with HSCT. When annual IRT price was reduced from $60 145 to below $29 469, IRT became the cost-effective strategy. Findings remained robust in sensitivity and probabilistic sensitivity analyses.

Conclusions and relevance: In the US, IRT is more expensive than HSCT for agammaglobulinemia treatment. The findings of this study suggest that IRT prevents more premature deaths but does not substantially increase quality of life relative to HSCT. Reducing US IRT cost by 51% to a value similar to IRT prices in countries implementing value-based pricing may render it the more cost-effective strategy.

Figure 1.. Cost Utility Acceptability Curve

Cost utility acceptability curve evaluating the percent of cost-effective iterations and various willingness-to-pay thresholds. Individual points at each willingness-to-pay threshold are connected to show trends. Vertical dashed lines indicate a standard US willingness-to-pay threshold of $100 000, and willingness-to-pay thresholds in which immunoglobulin replacement therapy becomes more cost-effective than matched unrelated donor (MUD) or matched sibling donor (MSD), respectively. K indicates thousands of dollars; QALY, quality-adjusted life-year.

Figure 2.. One-way Sensitivity Analyses of Immunoglobulin Replacement Therapy (IRT) Compared With Matched Sibling Donor (MSD) Hematopoietic Stem Cell Transplantation (HSCT)

One-way sensitivity analyses evaluating the association between individual parameter values and the incremental cost-effectiveness ratio (ICER) of IRT compared with MSD HSCT. Incremental cost-effectiveness ratios are indicated for high (white bars) and low (black bars) parameter ranges. The ICER of the base-case scenario is marked by the black vertical line (expected value [EV] = $282 166 for IRT vs MSD HSCT). The black dashed line marks where the ICER of IRT vs MSD HSCT crosses the willingness-to-pay (WTP) threshold of $100 000 per quality-adjusted life-year (QALY). The parameters of annual probability of death in long-term HSCT survivors and annual probability of death in patients with agammaglobulinemia at baseline are not depicted because, across the predefined ranges, the incremental effectiveness was 0, leading the ICER to approach infinity. These parameters did not shift cost-effectiveness rankings. GVHD indicates graft vs host disease; and M, millions of dollars. ^aParameters that shifted cost-utility rankings.

Figure 3.. Sensitivity Analyses of Immunoglobulin Replacement Therapy (IRT) vs Hematopoietic Stem Cell Transplant (HSCT) Costs

A, One-way sensitivity analysis of IRT annual cost vs the incremental cost-effectiveness ratio (ICER) of IRT compared with matched sibling donor (MSD) and matched unrelated donor (MUD) HSCT. The willingness-to-pay (WTP) threshold is $100 000. Gold vertical dashed lines indicate the IRT annual costs in the US compared with other countries. The solid gold lines indicate annual IRT cost at which the ICERs of IRT to MSD HSCT and MUD HSCT exceed the WTP threshold. B, Two-way sensitivity analyses show prices at which IRT is more cost-effective than MSD HSCT or MUD HSCT. The black dashed line depicts the current, most likely IRT annual cost and the corresponding minimum HSCT cost for IRT to be the more cost-effective therapy. Downward arrows at bottom left mark IRT prices at which IRT is always more cost-effective. Downward arrows at top right mark prices at which IRT is always dominated by MSD HSCT and MUD HSCT. K indicates thousands of dollars; M, millions of dollars; and QALY, quality-adjusted life-year.