Chu Paula, Mioc Jasmina, O'Donovan Peter, Henry Owen
Organon International GmbH, Lucerne, Switzerland.
Organon Canada, Kirkland, Québec, Canada.
Digestion. 2025;106(1):45-61. doi: 10.1159/000541326. Epub 2024 Sep 19.
Exocrine pancreatic insufficiency (EPI) is caused by multiple clinical conditions such as cystic fibrosis and chronic pancreatitis (CP). Standard management of EPI includes pancreatic enzyme replacement therapy (PERT) along with consultation with a dietitian. While PERTs have been on the market for several decades, newer publications on their clinical efficacy and safety raised the need for a comprehensive review of the literature. We aimed to identify the available evidence on the clinical efficacy and safety of treatments for EPI to understand the current treatment landscape and unmet need in patients with EPI.
A systematic literature review (SLR) was conducted in Embase, Medline, and Evidence-Based Medicine databases from 2010 to 2022; conference proceedings from 2020 to 2022 were also searched. Articles were screened independently by two reviewers at abstract and full-text stage against predefined eligibility criteria.
We identified 26 journal publications and two conference abstracts, reporting on 22 randomized control trials, four observational studies, and two single-arm interventional studies. The most reported treatment was pancrelipase, specifically Creon® (n = 12). Fourteen studies reported coefficient of fat absorption (CFA) results. Across studies, patients experienced a considerable increase in CFA post-initiation of treatment regardless of intervention or timepoint. Mean change in CFA ranged from 7.5% in patients with CP who received placebo to 36% in patients with CP treated with Creon®. Ten studies reported coefficient of nitrogen absorption (CNA). Where reported, pancrelipase (including Creon®) increased CNA levels in EPI patients compared to placebo. Only one study compared PERT brands head-to-head: no significant differences were reported in the CNA-72 h values (Creon® 82.0% [SE: 1.2] vs. Zenpep® 80.9% [SE: 1.2]). Loss of body weight and low body mass index (BMI) are important features of EPI. Overall, treatment with PERT increased BMI and body weight, or limited their decline, with increases ranging from 0.1 to 6.1 kg. Based on the 18 studies that reported safety outcomes, PERT was considered safe and well tolerated.
This SLR confirmed that PERT is an effective and tolerable treatment option for patients with EPI. However, nutritional parameters and health-related quality of life data were sparsely reported, and future clinical trials should look to incorporate these data given their importance in clinical practice and patient outcomes.
Exocrine pancreatic insufficiency (EPI) is caused by multiple clinical conditions such as cystic fibrosis and chronic pancreatitis (CP). Standard management of EPI includes pancreatic enzyme replacement therapy (PERT) along with consultation with a dietitian. While PERTs have been on the market for several decades, newer publications on their clinical efficacy and safety raised the need for a comprehensive review of the literature. We aimed to identify the available evidence on the clinical efficacy and safety of treatments for EPI to understand the current treatment landscape and unmet need in patients with EPI.
A systematic literature review (SLR) was conducted in Embase, Medline, and Evidence-Based Medicine databases from 2010 to 2022; conference proceedings from 2020 to 2022 were also searched. Articles were screened independently by two reviewers at abstract and full-text stage against predefined eligibility criteria.
We identified 26 journal publications and two conference abstracts, reporting on 22 randomized control trials, four observational studies, and two single-arm interventional studies. The most reported treatment was pancrelipase, specifically Creon® (n = 12). Fourteen studies reported coefficient of fat absorption (CFA) results. Across studies, patients experienced a considerable increase in CFA post-initiation of treatment regardless of intervention or timepoint. Mean change in CFA ranged from 7.5% in patients with CP who received placebo to 36% in patients with CP treated with Creon®. Ten studies reported coefficient of nitrogen absorption (CNA). Where reported, pancrelipase (including Creon®) increased CNA levels in EPI patients compared to placebo. Only one study compared PERT brands head-to-head: no significant differences were reported in the CNA-72 h values (Creon® 82.0% [SE: 1.2] vs. Zenpep® 80.9% [SE: 1.2]). Loss of body weight and low body mass index (BMI) are important features of EPI. Overall, treatment with PERT increased BMI and body weight, or limited their decline, with increases ranging from 0.1 to 6.1 kg. Based on the 18 studies that reported safety outcomes, PERT was considered safe and well tolerated.
This SLR confirmed that PERT is an effective and tolerable treatment option for patients with EPI. However, nutritional parameters and health-related quality of life data were sparsely reported, and future clinical trials should look to incorporate these data given their importance in clinical practice and patient outcomes.
外分泌性胰腺功能不全（EPI）由多种临床病症引起，如囊性纤维化和慢性胰腺炎（CP）。EPI的标准治疗包括胰腺酶替代疗法（PERT）以及与营养师的咨询。虽然PERT已在市场上销售了几十年，但关于其临床疗效和安全性的最新出版物引发了对文献进行全面综述的需求。我们旨在确定有关EPI治疗的临床疗效和安全性的现有证据，以了解当前的治疗情况以及EPI患者未满足的需求。
在2010年至2022年期间对Embase、Medline和循证医学数据库进行了系统文献综述（SLR）；还检索了2020年至2022年的会议论文集。两名审稿人根据预先确定的纳入标准在摘要和全文阶段独立筛选文章。
我们确定了26篇期刊出版物和2篇会议摘要，报道了22项随机对照试验、4项观察性研究和2项单臂干预性研究。报道最多的治疗药物是胰脂肪酶，特别是慷彼申（Creon®）（n = 12）。14项研究报告了脂肪吸收系数（CFA）结果。在各项研究中，无论干预措施或时间点如何，患者在开始治疗后CFA均有显著增加。CFA的平均变化范围从接受安慰剂的CP患者的7.5%到接受慷彼申治疗的CP患者的36%。10项研究报告了氮吸收系数（CNA）。在有报告的情况下，与安慰剂相比，胰脂肪酶（包括慷彼申）可提高EPI患者的CNA水平。只有一项研究对PERT品牌进行了直接比较：在CNA - 72小时值方面未报告显著差异（慷彼申82.0% [标准误：1.2] 对 善胰达（Zenpep®）80.9% [标准误：1.2]）。体重减轻和低体重指数（BMI）是EPI的重要特征。总体而言，PERT治疗可增加BMI和体重，或限制其下降，增加范围为0.1至6.1千克。基于18项报告了安全性结果的研究，PERT被认为是安全且耐受性良好的。
本系统文献综述证实，PERT是EPI患者的一种有效且可耐受的治疗选择。然而，营养参数和与健康相关的生活质量数据报告较少，鉴于这些数据在临床实践和患者预后中的重要性，未来的临床试验应考虑纳入这些数据。
外分泌性胰腺功能不全（EPI）由多种临床病症引起，如囊性纤维化和慢性胰腺炎（CP）。EPI的标准治疗包括胰腺酶替代疗法（PERT）以及与营养师的咨询。虽然PERT已在市场上销售了几十年，但关于其临床疗效和安全性的最新出版物引发了对文献进行全面综述的需求。我们旨在确定有关EPI治疗的临床疗效和安全性的现有证据，以了解当前的治疗情况以及EPI患者未满足的需求。
在2010年至2022年期间对Embase、Medline和循证医学数据库进行了系统文献综述（SLR）；还检索了2020年至2022年的会议论文集。两名审稿人根据预先确定的纳入标准在摘要和全文阶段独立筛选文章。
我们确定了26篇期刊出版物和2篇会议摘要，报道了22项随机对照试验、4项观察性研究和2项单臂干预性研究。报道最多的治疗药物是胰脂肪酶，特别是慷彼申（Creon®）（n = 12）。14项研究报告了脂肪吸收系数（CFA）结果。在各项研究中，无论干预措施或时间点如何，患者在开始治疗后CFA均有显著增加。CFA的平均变化范围从接受安慰剂的CP患者的7.5%到接受慷彼申治疗的CP患者的36%。10项研究报告了氮吸收系数（CNA）。在有报告的情况下，与安慰剂相比，胰脂肪酶（包括慷彼申）可提高EPI患者的CNA水平。只有一项研究对PERT品牌进行了直接比较：在CNA - 72小时值方面未报告显著差异（慷彼申82.0% [标准误：1.2] 对 善胰达（Zenpep®）80.9% [标准误：1.2]）。体重减轻和低体重指数（BMI）是EPI的重要特征。总体而言，PERT治疗可增加BMI和体重，或限制其下降，增加范围为0.1至6.1千克。基于18项报告了安全性结果的研究，PERT被认为是安全且耐受性良好的。
本系统文献综述证实，PERT是EPI患者的一种有效且可耐受的治疗选择。然而,营养参数和与健康相关的生活质量数据报告较少，鉴于这些数据在临床实践和患者预后中的重要性，未来的临床试验应考虑纳入这些数据。
