Clinical efficacy and cost-effectiveness of lanthanum carbonate as second-line therapy in hemodialysis patients in Japan

Abstract

Background and objectives: Lanthanum carbonate (LC) is a nonaluminum, noncalcium phosphate binder that is effective for hyperphosphatemia in dialysis patients. However, its efficacy and cost-effectiveness as second-line therapy have not been fully examined.

Design, setting, participants, & measurements: We first conducted a multicenter, open-label, 16-week clinical trial to examine the effect of additive LC in 116 hemodialysis patients who had uncontrolled hyperphosphatemia with conventional phosphorus-lowering therapy alone. Based on these clinical data, a state transition model was developed to evaluate the benefits and costs associated with LC as second-line therapy. Reduced risks for cardiovascular morbidity and mortality among patients treated with LC arise through more of the population achieving the target phosphorus levels. Uncertainty was explored through sensitivity analysis.

Results: After 16 weeks of additive LC treatment, mean serum phosphorus levels decreased from 7.30 ± 0.90 to 5.71 ± 1.32 mg/dl, without significant changes in serum calcium or intact parathyroid hormone levels. A subsequent cost-effectiveness analysis showed that compared with conventional treatment, additive LC incurred an average additional lifetime cost of $22,054 per person and conferred an additional 0.632 quality-adjusted life years (QALYs). This resulted in an incremental cost-effectiveness ratio of $34,896 per QALY gained. Applying a cost-effectiveness threshold of $50,000 per QALY, a probabilistic sensitivity analysis showed that additive LC had a 97.4% probability of being cost-effective compared with conventional treatment.

Conclusions: Our results indicate that the use of LC as second-line therapy would be cost-effective among hemodialysis patients with uncontrolled hyperphosphatemia in Japan.

Figure 1.

Structure of state transition model. (A) Short-term phase representing 16 weeks of initial therapy. Patients receive either additional LC or conventional treatment and are distributed in each phosphorus range (<5, 5 to <6, 6 to <7, and ≥7 mg/dl). Patient numbers are shown for the base case. (B) Long-term phase representing clinical course after initial therapy. Each patient experiences one of the following clinical events: “no event,” “CVD event,” “fracture event,” and “CVD and fracture event.” Risks for CVD, fracture, and death are estimated from their age, achieved phosphorus levels, and history of experienced events. Patients who survived repeat the cycle until their death.

Figure 2.

Mean (±SE) serum phosphorus during the study.

Figure 3.

One-way sensitivity analysis of ICER for additive LC.

Figure 4.

(A) Simulation output (1000 trials) for cost-effectiveness of additive LC. (B) Cost-effectiveness acceptability curve showing the probability that additive LC is cost-effective at various levels of willingness to pay.