Cost-effectiveness of tolvaptan in autosomal dominant polycystic kidney disease

Abstract

Chinese translation

Background: In the TEMPO (Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes) trial, tolvaptan significantly reduced expansion of kidney volume and loss of kidney function.

Objective: To determine how the benefits of tolvaptan seen in TEMPO may relate to longer-term health outcomes, such as progression to end-stage renal disease (ESRD) and death, and cost-effectiveness.

Design: A decision-analytic model.

Data sources: Published literature from 1993 to 2012.

Target population: Persons with early autosomal dominant polycystic kidney disease.

Time horizon: Lifetime.

Perspective: Societal.

Intervention: Patients received tolvaptan therapy until death, development of ESRD, or liver complications or no tolvaptan therapy.

Outcome measures: Median age at ESRD onset, life expectancy, discounted quality-adjusted life-years and lifetime costs (in 2010 U.S. dollars), and incremental cost-effectiveness ratios.

Results of base-case analysis: Tolvaptan prolonged the median age at ESRD onset by 6.5 years and increased life expectancy by 2.6 years. At $5760 per month, tolvaptan cost $744 100 per quality-adjusted life-year gained compared with standard care.

Results of sensitivity analysis: For patients with autosomal dominant polycystic kidney disease that progressed more slowly, the cost per quality-adjusted life-year gained was even greater for tolvaptan.

Limitation: Although TEMPO followed patients for 3 years, the main analysis assumed that clinical benefits persisted over patients' lifetimes.

Conclusion: Assuming that the benefits of tolvaptan persist in the longer term, the drug may slow progression to ESRD and reduce mortality rates. However, barring an approximately 95% reduction in price, cost-effectiveness does not compare favorably with many other commonly accepted medical interventions.

Primary funding source: National Institutes of Health and Agency for Healthcare Research and Quality.

Figure 1. Decision Analytic Model Design

Schematic of the Markov model of kidney disease. Stage 3 chronic kidney disease (CKD) was subdivided into stages 3a and 3b (not shown in the schematic). We used SAS 9.2 (SAS Institute Inc.) in our microsimulation to convert eGFR progression to CKD stage progression in autosomal dominant polycystic kidney disease (ADPKD) and then used TreeAge Pro 2009 (TreeAge Software Inc.) to perform cost-effectiveness analyses. “ESRD” is end-stage renal disease.

Figure 2. Simulated Mortality and Age of End-Stage Renal Disease (ESRD) Onset With and Without Tolvaptan

Tolvaptan therapy prolongs median age to development of ESRD by 6.5 years and extends life by an average of 2.6 years.

Figure 3. Cost-Effectiveness under Different Model Assumptions

Tolvaptan is less cost-effective with slower rates of baseline kidney disease progression. Tolvaptan cost less than $100,000 per quality-adjusted life year (QALY) gained if 95 mg per day is offered at or below $1,155 per month (approximately where the dotted $100,000 WTP line crosses the lines for men and women). The decline in estimated glomerular filtration rate (eGFR) from a cohort of patients with autosomal dominant polycystic kidney disease (ADPKD) was –2.4 ml/min/1.73m²/year.(3) Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and its Outcomes (TEMPO) trial/base case decline in eGFR of –3.7 ml/min/1.73m²/year observed in placebo group of the TEMPO trial.(7) “WTP” is willingness to pay. The horizontal $50,000 and $100,000 WTP lines represent societal willingness to pay thresholds – the amount of money society would be willing to pay to increase quality-adjusted life expectancy by one year. Assumed base case cost of $5,760 per month for 95mg of tolvaptan equals the current cost of 30mg tablets. Cost of 95 mg of tolvaptan is $18,240 based on current cost of 30mg tablets.