Cost-Effectiveness of Difelikefalin for the Treatment of Moderate-to-Severe Chronic Kidney Disease-Associated Pruritus (CKD-aP) in UK Adult Patients Receiving In-Centre Haemodialysis

Background and objectives CKD-associated pruritus (CKD-aP) is a serious, systemic comorbidity occurring in CKD patients. Despite the burden of CKD-aP, there are limited efficacious treatments available for its management; difelikefalin is the only approved treatment based on efficacy and safety demonstrated in the KALM-1 and KALM-2 clinical trials. The objective of this study was to assess the cost-effectiveness of difelikefalin with best supportive care (BSC) versus BSC alone for the treatment of moderate-to-severe CKD-aP in patients receiving in-centre haemodialysis from a UK NHS perspective. Methodology A de novo lifetime Markov health economic model was developed to assess the cost-effectiveness of difelikefalin. Modelled treatment efficacy was based on patient-level data from the pooled KALM-1 and KALM-2 trials. Total 5-D Itch scale score was used as the main efficacy driver in the model. Transition matrices were derived from per-cycle probabilities of changing health states defined by CKD-aP severity, estimated using the mean change from baseline in total 5-D Itch score. Time-dependent annual probabilities of death and transplant were estimated for people on haemodialysis. An increased risk of mortality for modelled patients with very severe, severe, or moderate CKD-aP was applied. Health state utilities and management costs were based on published evidence. Results Modelled patients treated with difelikefalin were estimated to have a reduced severity of CKD-aP. Consequently, treatment with difelikefalin and BSC compared with BSC alone was associated with increased life expectancy (0.11 years per person), and improved HRQoL which translated to in-creased quality adjusted life years (QALYs, 0.26 per person) gained compared with BSC alone. Improved patient outcomes were achieved at an incremental cost of £7,814 per person. Conclusion Overall, at a price of £31.90/vial, difelikefalin was estimated to be a cost-effective treatment for CKD-aP at a willingness-to-pay threshold of £30,000/QALY, with conclusions robust to sensitivity analysis.