Department of Gastroenterology and Hepatology, University Hospital Zürich, Zürich, Switzerland.
Department of Medicine 1, University Hospital Erlangen and Friedrich-Alexander University of Erlangen-Nürnberg, Erlangen, Germany.
Liver Int. 2022 Jan;42(1):112-123. doi: 10.1111/liv.15039. Epub 2021 Aug 26.
BACKGROUND & AIMS: Primary biliary cholangitis (PBC) can result in life-altering cholestatic pruritus and fatigue, but treatment options are limited. Seladelpar, a peroxisome proliferator-activated receptor-delta (PPARδ) agonist, has demonstrated potent anti-cholestatic effects in clinical studies. This open-label, uncontrolled phase 2 study in PBC patients evaluated the effects of 1-year of seladelpar treatment on measures of pruritus and quality of life.
Self-reported experiences of 101 PBC patients were collected at baseline and after 1 year of seladelpar treatment using the pruritus visual analog scale (VAS), 5D-itch scale, and PBC-40 questionnaires along with bile acid profiles.
In patients with moderate-to-severe pruritus, substantial improvement in pruritus was seen in 58% and 93% of patients in 5/10 mg and 10 mg treatment groups, respectively. After 1 year, patients reporting improvement substantially outnumbered those who worsened in the total 5-D itch (including individual domains) and PBC-40 (itch and fatigue domains) questionnaires. Improvement in sleep disturbance at 1-year was reported in 81% (5/10 mg) and 78% (10 mg) of the patients with baseline itch-related sleep disturbance by 5-D itch score with similar results using the PBC-40 sleep questionnaire. Seladelpar-treated patients had significant reductions of 46% (5/10 mg) and 31% (10 mg) in the serum bile acid precursor C4 and reductions of up to 38% in serum bile acids.
Seladelpar treatment for 1 year led to consistent improvement in both symptom burden and biochemical response, suggesting its potential as a single agent to address two key unmet needs in PBC patients.
原发性胆汁性胆管炎（PBC）可导致改变生活的胆汁淤积性瘙痒和疲劳，但治疗选择有限。过氧化物酶体增殖物激活受体-δ（PPARδ）激动剂 Seladelpar 在临床研究中显示出强大的抗胆汁淤积作用。这项在 PBC 患者中进行的开放标签、非对照 2 期研究评估了 Seladelpar 治疗 1 年对瘙痒和生活质量衡量指标的影响。
在接受 Seladelpar 治疗 1 年后，101 例 PBC 患者通过瘙痒视觉模拟量表（VAS）、5D-itch 量表和 PBC-40 问卷以及胆汁酸谱，报告了 101 例 PBC 患者的自我报告体验。
在中重度瘙痒患者中，5/10mg 和 10mg 治疗组分别有 58%和 93%的患者瘙痒显著改善。1 年后，在总 5-D itch（包括各个领域）和 PBC-40（瘙痒和疲劳领域）问卷中，报告改善的患者明显多于恶化的患者。根据 5-D itch 评分，基线瘙痒相关睡眠障碍的 81%（5/10mg）和 78%（10mg）患者报告 1 年后睡眠障碍改善，使用 PBC-40 睡眠问卷也有类似结果。Seladelpar 治疗的患者血清胆汁酸前体 C4 降低 46%（5/10mg）和 31%（10mg），血清胆汁酸降低高达 38%。
Seladelpar 治疗 1 年可显著改善症状负担和生化反应，这表明它有可能成为一种单一药物，解决 PBC 患者的两个主要未满足需求。
