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

<b>Background/Objectives</b>: CKD-associated pruritus (CKD-aP) is a serious systemic comorbidity occurring in patients with CKD. Despite the burden of CKD-aP, there are limited efficacious treatments available for its management; difelikefalin is the only approved treatment based on its efficacy and safety demonstrated in two clinical studies, namely KALM-1 and KALM-2. This study aimed to evaluate the cost-effectiveness of difelikefalin plus best supportive care (BSC) versus BSC alone when treating moderate-to-severe CKD-aP in patients receiving in-centre haemodialysis, from the perspective of the UK healthcare system. <b>Methods</b>: A de novo lifetime Markov health economic model was built to assess the cost-effectiveness of difelikefalin. The modelled efficacy of difelikefalin was based on data from KALM-1 and KALM-2 pooled at the patient level. The main efficacy driver was the total 5-D Itch scale score. Per-cycle probabilities of changing health states defined by CKD-aP severity were used to derive transition matrices; the model also estimated time-dependent annual probabilities of death and transplant 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. <b>Results</b>: Modelled patients treated with difelikefalin were estimated to have a reduced severity of CKD-aP. Consequently, difelikefalin plus BSC was associated with an increased life expectancy of 0.11 years per person and improved HRQoL compared with BSC alone. This translated to higher quality-adjusted life years, at 0.26 per person gained compared to BSC alone. Improved patient outcomes were achieved at an incremental cost of £7814 per person. <b>Conclusions</b>: Overall, at a price of £31.90/vial, difelikefalin was estimated to be a cost-effective treatment for moderate-to-severe CKD-aP at a willingness-to-pay threshold of £30,000/QALY, with conclusions robust to sensitivity analysis.