在一项定性访谈研究中，长期吉福昔兰治疗前后急性肝性卟啉的患者经验。

IF 1.8 4区医学 Q3 GENETICS & HEREDITY

Molecular Genetics and Metabolism Reports Pub Date : 2024-12-20 DOI:10.1016/j.ymgmr.2024.101174

Hetanshi Naik , Michelle Brown , Stephen Meninger , Stephen Lombardelli

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引用次数: 0

摘要

背景：急性肝性卟啉症（AHP）的特点是衰弱和潜在危及生命的神经内脏发作，可能的慢性症状和长期并发症。在1/2期开放标签扩展（OLE）研究和3期ENVISION研究中，givosiran导致年化发作率和生活质量（QOL）指标的持续改善。为了了解患者对AHP的症状和影响的体验，以及在使用吉伏西兰治疗期间经历的任何变化，对研究参与者进行了定性访谈。方法：在完成1/2期OLE研究和3期ENVISION研究后继续接受吉弗西兰治疗的参与者参加了由RTI Health Solutions开发和执行的2022年半结构化访谈（即关于预定主题的松散结构化访谈，没有严格遵守措辞或问题顺序）。使用主题分析方法评估转录本。作者/研究者根据参与者的描述将症状分类为急性发作相关或慢性发作。从访谈参与者中选择临床试验结果（来自1/2期和ENVISION研究的基线特征和生活质量评分）进行汇编。结果：在访谈时，21名参与者的给予西兰治疗持续时间约为4-5年(平均[SD]， 51.8[7.9]个月；中位[范围]，49.7[41.4,69.1]个月)。参与者报告在1/2期OLE或3期研究之前出现AHP症状，包括腹痛（n = 20/21[95%]）和疲劳（n = 20/21[95%]），影响包括工作/学校（n = 21/21[100%]）以及家庭和亲密关系（n = 20/21[95%]）。治疗后，参与者报告症状改善，包括腹痛（n = 20/20[100%]参与者）、疲劳（n = 20/20[100%]）和恶心（n = 19/19[100%]），以及影响，包括家庭和亲密关系（n = 20/20[100%]）和工作/学校（n = 19/21[90%]）。大多数参与者（n = 19/21[90%]）在试验前使用阿片类药物，许多人报告停用阿片类药物（n = 10/17[59%]）或使用较低剂量（n = 4/17[24%]）。参与者报告某些症状完全缓解，包括呕吐（n = 8/11[73%]）、恶心（n = 10/15[67%]）和腹痛（n = 8/19[42%]）。疼痛完全缓解或停止使用阿片类药物的参与者往往更年轻，诊断时间也更晚，在临床试验期间，他们的基线EuroQOL视觉模拟量表得分更高。在临床试验开始前进行过血凝素预防的参与者更有可能在研究前经历过腹痛、神经性疼痛/感觉异常和胃肠道症状，并且通常更有可能或同样有可能完全缓解这些症状（例如，n = 6/8[75%]先前进行过血凝素预防的参与者报告腹痛完全缓解，而n = 2/11[18%]未进行过血凝素预防的参与者报告腹痛完全缓解）。所有参与者都表示对吉伏西兰“非常满意”。结论：参与者报告了AHP症状有意义的改善，生活质量增加，并减少了长期每月给予吉弗西兰治疗的阿片类药物的使用。

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Patient experience with acute hepatic porphyria before and after long-term givosiran treatment in a qualitative interview study

Background

Acute hepatic porphyria (AHP) is characterized by debilitating and potentially life-threatening neurovisceral attacks, possible chronic symptoms, and long-term complications. In a phase 1/2 open-label extension (OLE) study and the phase 3 ENVISION study, givosiran led to sustained improvement in annualized attack rate and quality of life (QOL) measures. To capture the patient experience of symptoms and impacts of AHP, and any changes experienced during treatment with givosiran, qualitative interviews were conducted with study participants.

Methods

Participants who continued givosiran treatment after completing the phase 1/2 OLE study and the phase 3 ENVISION study participated in semi-structured interviews (i.e., loosely structured interviews on a predetermined topic without strict adherence to wording or order of questions) in 2022 that were developed and executed by RTI Health Solutions. Transcripts were assessed using thematic analysis methods. Authors/investigators categorized symptoms as likely acute attack-related or chronic based on the participants' descriptions. Select clinical trial results (baseline characteristics and QOL scores from the phase 1/2 and ENVISION studies) from interview participants were compiled.

Results

Duration of givosiran treatment in the 21 participants at the time of interview was approximately 4–5 years (mean [SD], 51.8 [7.9] months; median [range], 49.7 [41.4, 69.1] months). Participants reported experiencing AHP symptoms prior to the phase 1/2 OLE or phase 3 studies, including abdominal pain (n = 20/21 [95 %]) and fatigue (n = 20/21 [95 %]), with impacts including work/school (n = 21/21 [100 %]) and family and intimate relationships (n = 20/21 [95 %]). Post-treatment, participants reported improvements in symptoms including abdominal pain (n = 20/20 [100 %] participants), fatigue (n = 20/20 [100 %]), and nausea (n = 19/19 [100 %]), and in impacts, including family and intimate relationships (n = 20/20 [100 %]) and work/school (n = 19/21 [90 %]). Most participants (n = 19/21 [90 %]) used opioids prior to the trials, and many reported stopping opioids (n = 10/17 [59 %]) or using a lower dose (n = 4/17 [24 %]). Participants reported complete relief of certain symptoms, including vomiting (n = 8/11 [73 %]), nausea (n = 10/15 [67 %]), and abdominal pain (n = 8/19 [42 %]). Participants with complete relief of pain or cessation of opioid use tended to be younger and more recently diagnosed, with higher baseline EuroQOL visual analog scale scores during the clinical trials. Participants with prior hemin prophylaxis at entry into the clinical trials were more likely to have experienced abdominal pain, neuropathic pain/paresthesia, and gastrointestinal symptoms before the study, and were generally more or as likely to have complete relief of these symptoms (e.g., n = 6/8 [75 %] participants with prior hemin prophylaxis reported complete relief of abdominal pain vs n = 2/11 [18 %] participants without prior hemin prophylaxis). All participants reported being “very satisfied” with givosiran.

Conclusions

Participants reported meaningful improvements in AHP symptoms, increased QOL, and reduced opioid use with long-term monthly givosiran treatment.

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来源期刊

Molecular Genetics and Metabolism Reports Biochemistry, Genetics and Molecular Biology-Endocrinology

CiteScore

4.00

自引率

5.30%

发文量

105

审稿时长

33 days

期刊介绍： Molecular Genetics and Metabolism Reports is an open access journal that publishes molecular and metabolic reports describing investigations that use the tools of biochemistry and molecular biology for studies of normal and diseased states. In addition to original research articles, sequence reports, brief communication reports and letters to the editor are considered.