Long-term efficacy and safety of nalfurafine hydrochloride on pruritus in chronic liver disease patients: Patient-reported outcome based analyses

Background and aimAmong various symptoms accompanied with chronic liver disease, pruritus affects the quality of life of patients, causing physical and mental stress, and worsens hepatic function. Recently, κ-opioid receptor agonist, nalfurafine hydrochloride was approved to treat central pruritus in patients with liver disease in Japan. This study aimed to assess the long-term efficacy and safety of nalfurafine hydrochloride on pruritus in chronic liver disease patients.MethodsA patient-reported outcome using questionnaire-based methods was used for 41 liver disease patients with or without pruritus symptoms. Nalfurafine hydrochloride (2.5 μg/day) was orally administered to 18 patients suffering from pruritus symptoms and whose current treatment was not effective. The same questionnaires and visual analogue scales (VAS) were repeatedly followed up for the patients for the entire follow-up period, and biochemical analyses were performed to evaluate the safety of the treatment.ResultsPruritus completely disappeared in seven of 18 cases, and VAS scores showed a decreasing trend over time from the start of nalfurafine hydrochloride administration in all patients who received the medication. Among 11 patients who were followed up for more than 12 weeks, nine patients showed continuous improvement of symptoms, and this progress was still apparent at ≥20 weeks after starting administration (p ConclusionsNalfurafine hydrochloride contributed to long-term suppression of pruritus without significant safety problems.

研究背景与目的
在慢性肝病（chronic liver disease）伴随的各类临床症状中，瘙痒（pruritus）会显著降低患者的生活质量，引发身心双重应激，同时加重肝功能损伤。近期，κ阿片受体激动剂（κ-opioid receptor agonist）盐酸纳呋拉啡（nalfurafine hydrochloride）已在日本获批用于治疗肝病患者的中枢性瘙痒。本研究旨在评估盐酸纳呋拉啡用于慢性肝病患者瘙痒症状的长期疗效与安全性。

研究方法
本研究采用基于问卷的患者报告结局（patient-reported outcome）评估方案，纳入41名伴或不伴瘙痒症状的肝病患者。对18名当前治疗方案无效的瘙痒症患者，予以口服盐酸纳呋拉啡，给药剂量为每日2.5μg。在整个随访周期内，对所有患者重复开展相同问卷与视觉模拟评分法（visual analogue scales, VAS）评估，并通过生化分析评估本次治疗的安全性。

研究结果
18名接受治疗的患者中，7名的瘙痒症状完全消失；所有用药患者的VAS评分自给药起始后均随时间呈下降趋势。在随访时长超过12周的11名患者中，9名患者的症状呈持续改善，且该改善趋势在给药起始后≥20周时仍较为显著（p

研究结论
盐酸纳呋拉啡可长期抑制慢性肝病患者的瘙痒症状，且未出现显著的安全性问题。