A pilot study of vidofludimus calcium for treatment of primary sclerosing cholangitis.
A pilot study of vidofludimus calcium for treatment of primary sclerosing cholangitis.
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DOI：
10.1002/hep4.1926
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发表时间：
2022-07
影响因子：
5.1
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中科院分区：
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本初步研究的目的是探讨静脉滴钙剂（VC）治疗原发性硬化性胆管炎（PSC）的疗效、安全性和耐受性。这是一项单臂、开放标签的先导研究，纳入了18例PSC患者。研究患者接受VC治疗6个月。该研究在两个地点进行，梅奥诊所，罗切斯特，明尼苏达州和梅奥诊所，凤凰城，亚利桑那州。研究的主要终点是研究结束时血清碱性磷酸酶（ALP）的改善。次要终点包括评估其他肝脏生物标志物（胆红素、丙氨酸转氨酶和天冬氨酸转氨酶）。在入组的18名患者中，11名完成了6个月的研究治疗。完成治疗的患者与未完成治疗的患者在基线时的直接胆红素水平相似（平均±SD， 0.4±0.3对0.1±0.1,p = 0.04）。通过意向治疗分析，16.7%（3/18）的患者达到了主要结局。通过每个方案分析，仅包括完成治疗的患者，27.7%（3/11）的患者在第24周出现ALP正常化（95%置信区间，6.0%至61.0%）。VC耐受性良好，无药物相关的严重不良事件。结论：该概念验证研究为进一步探索PSC患者的VC提供了支持。Vidofludimus钙（一种新型DHODH抑制剂）的开放标签试点试验显示，大量患者的碱性磷酸酶降低。Vidofludimus钙值得在该疾病中进行更大规模的随机对照试验。
The purpose of this pilot study was to explore the efficacy, safety, and tolerability of vidofludimus calcium (VC) in the treatment of primary sclerosing cholangitis (PSC). This was a single‐arm open‐label pilot study with a cohort of 18 patients with PSC. Study patients received VC for a period of 6 months. The study was undertaken at two sites, Mayo Clinic, Rochester, MN, and Mayo Clinic, Phoenix, AZ. The primary endpoint of the study was improvement of serum alkaline phosphatase (ALP) at the end of the study. Secondary endpoints included assessment of other liver biomarkers (bilirubin, alanine aminotransferase, and aspartate aminotransferase). Of 18 patients enrolled, 11 completed the 6 months of study treatment. Patients who completed treatment versus those who did not were similar other than a significantly higher direct bilirubin at baseline in the group that completed treatment (mean ± SD, 0.4 ± 0.3 versus 0.1 ± 0.1, p = 0.04). By intent to treat analysis, the primary outcome was met in 16.7% (3/18) of patients. By per‐protocol analysis, including only patients who completed treatment, normalization of ALP occurred in 27.7% (3/11) at week 24 (95% confidence interval, 6.0% to 61.0%). VC was well tolerated with no drug‐related serious adverse events. Conclusion: This proof of concept study provides support for further exploration of VC in patients with PSC. This open‐label pilot trial of Vidofludimus calcium, a novel DHODH inhibitor, shows reduction in alkaline phosphatase in a significant number of patients. Vidofludimus calcium deserves further study with larger, randomized, controlled trials in this disease.