Supplementary Material for: The efficacy and safety of intravenous difelikefalin for the treatment of pruritus in patients undergoing hemodialysis: a systematic review and meta-analysis of randomized controlled trials

Introduction: Chronic kidney disease-associated pruritus (CKD-aP) is a common and distressing symptom in end-stage renal disease (ESRD) patients undergoing hemodialysis (HD), significantly impairing quality of life. This meta-analysis evaluates the efficacy and safety of difelikefalin for CKD-aP. Methods: We systematically searched PubMed, Embase, Cochrane Library, Web of Science, and Scopus for randomized controlled trials (RCTs) on difelikefalin in HD patients up to November 19, 2024. Risk of bias was assessed using the Cochrane tool. Data were analyzed using Stata 15.1, with results expressed as risk ratios (RR) or mean differences (MD) with 95% confidence intervals (CI). Results: Five RCTs involving 937 HD patients were included. Difelikefalin significantly reduced weekly average WI-NRS score (MD: −0.41 [−0.51, −0.31]), 5-D Itch Scale (MD: −0.42 [−0.53, −0.31]), Skindex-10 (MD: −0.42 [−0.58, −0.26]), and Skindex-16 (MD: −0.16 [−0.23, −0.00]). It also increased the proportion achieving WI-NRS improvement ≥3 points (RR: 1.29), ≥4 points (RR: 1.45), and patient global impression of change (PGIC) response (RR: 1.44) (all p 0.05). Discussion: Difelikefalin is effective in reducing moderate-to-severe CKD-aP in HD patients, though it may increase non-serious adverse events. Limitations include limited evidence and short-term follow-up. Larger, multi-center RCTs are needed to confirm long-term safety and efficacy.引言：慢性肾脏病相关性瘙痒（Chronic kidney disease-associated pruritus, CKD-aP）是接受血液透析（hemodialysis, HD）的终末期肾病（end-stage renal disease, ESRD）患者常见且令人痛苦的临床症状，可显著损害患者生活质量。本项荟萃分析旨在评估地夫利芬（difelikefalin）用于治疗慢性肾脏病相关性瘙痒的有效性与安全性。 方法：我们系统检索了PubMed、Embase、Cochrane图书馆、Web of Science及Scopus数据库，检索时限截至2024年11月19日，筛选所有关于血液透析患者使用地夫利芬治疗的随机对照试验（randomized controlled trial, RCT）。采用Cochrane偏倚风险工具评估纳入研究的偏倚风险，使用Stata 15.1软件进行数据分析，结果以风险比（risk ratio, RR）、均数差（mean difference, MD）及95%置信区间（confidence interval, CI）进行报告。 结果：最终纳入5项随机对照试验，共包含937例血液透析患者。地夫利芬可显著降低患者的每周平均WI-NRS评分（MD：-0.41，95%CI[-0.51, -0.31]）、5-D瘙痒量表评分（MD：-0.42，95%CI[-0.53, -0.31]）、Skindex-10评分（MD：-0.42，95%CI[-0.58, -0.26]）及Skindex-16评分（MD：-0.16，95%CI[-0.23, -0.00]）。同时，其可提升达到WI-NRS评分改善≥3分（RR：1.29）、≥4分（RR：1.45）及患者总体症状变化印象（patient global impression of change, PGIC）应答率的患者比例（所有P<0.05）。 讨论：地夫利芬可有效改善血液透析患者的中重度慢性肾脏病相关性瘙痒，但可能增加非严重不良事件的发生风险。本研究存在局限性，包括纳入证据总量有限、随访周期较短，未来需开展大样本、多中心随机对照试验以验证其长期安全性与有效性。