Difelikefalin 50micrograms/1ml solution for injection vials

Background and ObjectiveUremic pruritus is a persistent condition that is difficult to cure in patients with end-stage renal disease who are having regular dialysis. It is highly prevalent, and current therapies have limited effectiveness and can cause significant adverse effects. Several trials have provided evidence that difelikefalin can be an effective treatment for uremic pruritus, with few side responses. However, it is important to note that the available evidence is limited. This study collected published randomized controlled trials for systematic review and Meta-analysis, to explore the efficacy and safety of difelikefalin treating uremic pruritus and to provide evidence-based medical evidence for clinical treatment.MethodsA systematic literature search was conducted in PubMed, EMBASE, Web of Science, the Cochrane Library Data from building libraries to 6 January 2024. We extracted data from eligible studies to analyze the efficacy and safety of difelikefalin in the treatment of hemodialysis patients with pruritus.ResultsThis study comprised 9 trials with 4,118 people. The meta-analysis demonstrated that difelikefalin is more effective than placebo in treating uremic pruritus. Specifically, difelikefalin resulted in a greater improvement in WI-NRS scores of at least 3 points from baseline (OR = 1.98) and at least 4 points from baseline (OR = 1.94). Additionally, difelikefalin led to a decrease in the total score of the 5-D itch scale (MD = 1.56), a decrease in the skindex-10 scale score (MD = 4.92), and a decrease in the WI-NRS scale score (MD = 0.91).ConclusionDifelikefalin demonstrates significant efficacy in alleviating pruritus in individuals suffering from uremia. Althogh it has adverse events, they are mild.

Abstract licence: CC BY 4.0

Background Chronic kidney disease–associated pruritus (CKD-ap) is a common complication that negatively affects the quality of life. Difelikefalin has emerged as a novel FDA-approved drug to manage CKD-ap. This systematic review and meta-analysis will assess the efficacy and safety of Difelikefalin versus placebo to manage CKD-ap.Methods PubMed, Scopus, WOS, Central, and Embase were systematically searched until November 2023. RevMan was used to perform meta-analysis. Quality assessment was conducted using the Cochrane RoB 2.0 tool. Results were reported as risk ratio (RR) and mean difference (MD) with a 95% confidence interval (CI). PROSPERO ID: (CRD42023485979).Results Five RCTs with a total of 896 participants were included. Difelikefalin significantly decreased the weekly mean WI-NRS score (MD: −0.99 [−1.22, −0.75], p ˂ .00001), 5-D itch scale total score (MD: −1.51 [−2.26, −0.76], p > .0001), and Skindex-10 total score (MD: −7.39 [−12.51, −2.28], p = .005), but showed significantly higher adverse events (RR: 1.26 [1.03, 1.55], p = .03), versus placebo. However, there was no significant difference between both groups in serious adverse events (RR: 1.42 [0.78, 2.57], p = .25) or death (RR: 0.81 [0.19, 3.34], p = .77).Conclusion Difelikefalin appears to be a promising agent for the management of CKD-induced pruritus in patients with end-stage renal disease. However, evidence is still underpowered due to the paucity of the current data; therefore, more robust RCTs are required to confirm the benefit of Difelikefalin.

Abstract licence: CC BY-NC 4.0

BackgroundUraemic pruritus (UP) is an increasingly significant health burden. However, current treatments are often unsatisfactory and associated with numerous adverse reactions. Recently, several large randomized controlled trials (RCTs) have confirmed that kappa opioid receptor (KOR) agonists, which target the endogenous opioid system, are effective in controlling symptoms. We compared the efficacy and safety of currently available KOR agonists for the treatment of UP.MethodsWe conducted a systematic review and network meta-analysis (NMA) of RCTs to assess the efficacy and safety of KOR agonists in patients with UP. The primary outcomes were pruritus-related scales and adverse events. Two independent reviewers evaluated RCTs for eligibility and extracted relevant data, with discrepancies resolved by consensus or a third reviewer. We utilized a fixed effects model within a Bayesian framework for the NMA. Dichotomous variables were presented as risk ratios (RRs) and continuous variables were merged using standardized mean differences. Statistical analyses were performed using R 4.2.3 and JAGS 4.3.0. The risk of bias was assessed using the RoB 2 tool and the certainty of findings was rated according to Grading of Recommendations Assessment, Development and Evaluation criteria. The study protocol was registered on PROSPERO (CRD42020169955).ResultsTen studies with 2483 participants were included. Concerning the primary endpoints, difelikefalin at doses of 0.25 µg/kg, 0.5 µg/kg, 1.0 µg/kg and 1.5 µg/kg, nalfurafine at 2.5 µg and 5 µg and nalbuphine at 120 mg were significantly effective in reducing itching severity compared with placebo. For the secondary endpoint, all four doses of difelikefalin were associated with higher rates of adverse events compared with placebo, while other interventions showed rates comparable to those of placebo and did not present statistically significant differences.ConclusionIn summary, difelikefalin at doses of 0.25 µg/kg and 0.5 µg/kg, along with nalfurafine at 0.25 µg/kg and 0.5 µg/kg, can be considered recommended therapeutic options for UP treatment.

Abstract licence: CC BY

Background: Chronic Kidney Disease (CKD) is a type of kidney disease that gradual loss of kidney function over a period of months or years, usually more than 3 months. Uremic pruritus or chronic kidney disease-associated with CKD (CKD-aP) is a common complication that experienced by CKD patients especially for patients undergoing haemodialysis and it will negatively impact quality of life, for example depression, poor sleep quality, and miss dialysis sessions.Methods: Three online databases were used for the literature search: Science Direct, Embase, and PubMed. obtaining the information in January 2024. Using specific keywords, a comprehensive analysis of research articles was carried out. We examined the safety and effectiveness of difelikefalin in the management of pruritus in patients receiving hemodialysis who have chronic kidney disease.Result: Six studies were evaluated that met the criteria for inclusion. The efficacy of difelikefalin in all studies was examined by using WI-NRS as assessment tools for the primary outcome, and for the secondary outcome, skindex-10 or skindex-16 scoring, the 5-D itch scale, and the itch MOS (Medical Outcome Study) sleep disturbance scale were used. From all studies, difelikefalin in various dosages and routes (oral and intravenous) improved pruritus reduction in hemodialysis patients with CKD over placebo. However, in the majority of cases, difelikefalin caused a higher chance of experiencing adverse events than in the placebo group.Conclusions: All studies show a greater pruritus reduction in hemodialysis patients receiving therapy over placebo, with the optimal benefit-risk at 0.5 μg/kg of difelikefalin, despite unclear efficacy-dosage connections.

Abstract licence: CC BY-SA 4.0

Chronic kidney disease-associated pruritus (CKD-aP) is a chronic condition that significantly reduces the quality of life of patients with end-stage renal disease. The etiology is not fully understood, but imbalance in the activity of the opioid pathways, including downregulation of the kappa-opioid receptor, may contribute to itching sensation. Difelikefalin is a selective, peripherally acting kappa-opioid receptor (KOR) agonist. Recently, difelikefalin has been approved as a first drug for the treatment of pruritus associated with chronic kidney disease (CKD) in adult hemodialysis patients. A systematic review of currently available clinical trials was performed to assess the efficacy and safety of difelikefalin in patients with uremic pruritus. A literature review was conducted in May 2022 based on the PRISMA 2020 guidelines. The analyzed clinical trials showed that difelikefalin was effective in reducing pruritus in patients as assessed by the Worst Itching Intensity Numerical Rating Scale. Improvement in quality of life assessed on the basis of the Skindex score and the 5-D itch scale was also noticed. The most commonly reported side effects were mild and included nausea, vomiting, dizziness, and diarrhea. Due to its proven efficacy and good safety profile, difelikefalin is a promising drug for the treatment of pruritus in patients with chronic kidney disease.

Abstract licence: CC BY 4.0