Global Medical Affairs, Pfizer, Ixelles, Belgium.
Developmental Endocrinology Research Group, School of Medicine, University of Glasgow, Glasgow, United Kingdom.
Front Endocrinol (Lausanne). 2022 Mar 1;13:795224. doi: 10.3389/fendo.2022.795224. eCollection 2022.
Pediatric patients with growth hormone deficiency (GHD) are currently treated with daily injections of recombinant human growth hormone (rhGH) to promote linear growth and enable attainment of normal adult height. One of the main reasons for suboptimal growth during rhGH therapy is non-adherence to treatment. The objective of this systematic literature review was to examine the recent literature on pediatric adherence to injectable treatments for chronic conditions (focusing on rhGH) to characterize levels of adherence and identify the factors/barriers associated with adherence.
The Embase and MEDLINE databases (January 2015-October 2020) were searched to identify publications describing studies of pediatric patients (aged ≤17 years) with GHD and other chronic conditions requiring daily or weekly injectable treatments; a similar targeted search of Chinese literature was also performed. Adherence data were extracted from the included studies and summarized. Risk of bias was determined using the Cochrane Risk of Bias tool 2 or the Newcastle-Ottawa Scale.
A total of 23 publications were included, with all publications except for one (multiple sclerosis) focused on pediatric GHD studies: there were two clinical trials, 18 observational studies and three survey studies. Study sample sizes ranged from 30 to 13,553 patients (median: 95 patients). The definition of adherence varied between studies and included mean adherence rate, median adherence rate, and the percentage of patients within pre-specified adherence categories. Of the publications assessing adherence to daily rhGH, 11 studies reported 12-month mean adherence rate (range: 73.3%- 95.3%) and eight studies reported median adherence (range: 91%- 99.2%). The barriers to treatment adherence identified included self-administration, increased administration frequency, age (adolescence), longer treatment duration, device design, and insufficient family education, awareness, and/or engagement. Recommendations for increasing adherence included using adherence reminder tools, increasing patient engagement/education, and improving injection device design and drug product.
Adherence to rhGH treatment was high (>80%) for many studies, though comparability between studies was limited given the substantial heterogeneity in the way adherence was defined, measured, and reported. To address this heterogeneity, we recommend standardizing how adherence is defined and reported and encourage the use of standardized study designs and outcome measures.
患有生长激素缺乏症（GHD）的儿科患者目前接受重组人生长激素（rhGH）的每日注射治疗，以促进线性生长并达到正常成人身高。rhGH 治疗期间生长不理想的主要原因之一是治疗不依从。本系统文献综述的目的是检查有关儿科患者（≤17 岁）慢性疾病（重点为 rhGH）注射治疗依从性的最新文献，以描述依从性水平并确定与依从性相关的因素/障碍。
检索了 Embase 和 MEDLINE 数据库（2015 年 1 月至 2020 年 10 月），以确定描述患有 GHD 和其他需要每日或每周注射治疗的慢性疾病的儿科患者研究的出版物；还对中文文献进行了类似的有针对性搜索。从纳入的研究中提取了依从性数据并进行了总结。使用 Cochrane 偏倚风险工具 2 或纽卡斯尔-渥太华量表确定了偏倚风险。
共纳入 23 篇出版物，除一篇（多发性硬化症）外，所有出版物均聚焦于儿科 GHD 研究：其中两项临床试验，18 项观察性研究和三项调查研究。研究样本量从 30 到 13553 例患者不等（中位数：95 例）。研究之间的依从性定义各不相同，包括平均依从率、中位数依从率以及特定依从性分类内的患者百分比。在评估每日 rhGH 依从性的出版物中，有 11 项研究报告了 12 个月的平均依从率（范围：73.3%-95.3%），8 项研究报告了中位数依从率（范围：91%-99.2%）。治疗依从性的障碍包括自我管理、增加给药频率、年龄（青春期）、治疗时间延长、器械设计以及缺乏充分的家庭教育、意识和/或参与。提高依从性的建议包括使用依从性提醒工具、增加患者参与/教育以及改进注射设备设计和药物产品。
许多研究报告 rhGH 治疗的依从性很高（>80%），但由于依从性的定义、测量和报告方式存在很大差异，因此研究之间的可比性有限。为了解决这种异质性，我们建议标准化依从性的定义和报告方式，并鼓励使用标准化的研究设计和结果衡量标准。
