Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden; Pediatric Endocrinology Unit, Karolinska University Hospital, Solna, Sweden.
Institute of Cancer Research, London, UK.
Lancet Diabetes Endocrinol. 2020 Aug;8(8):683-692. doi: 10.1016/S2213-8587(20)30163-7.
Recombinant human growth hormone has been used for more than 30 years and its indications have increased worldwide. There is concern that this treatment might increase mortality, but published data are scarce. We present data from the entire dataset of all eight countries of the Safety and Appropriateness of Growth hormone treatments in Europe (SAGhE) consortium, with the aim of studying long-term overall and cause-specific mortality in young adult patients treated with recombinant human growth hormone during childhood and relating this to the underlying diagnosis.
This cohort study was done in eight European countries (Belgium, France, Germany, Italy, The Netherlands, Sweden, Switzerland, and the UK). Patients were classified a priori based on pre-treatment perceived mortality risk from their underlying disease and followed up for cause-specific mortality. Person-years at risk of mortality and expected rates from general population data were used to calculate standardised mortality ratios (SMRs).
The cohort comprised 24 232 patients treated with recombinant human growth hormone during childhood, with more than 400 000 patient-years of follow-up. In low-risk patients with isolated growth hormone deficiency or idiopathic short stature, all-cause mortality was not significantly increased (SMR 1·1, 95% CI 0·9-1·3). In children born small for gestational age, all-cause mortality was significantly increased when analysed for all countries (SMR 1·5, CI 1·1-1·9), but this result was driven by the French subcohort. In patients at moderate or high risk, mortality was increased (SMR 3·8, 3·3-4·4; and 17·1, 15·6-18·7, respectively). Mortality was not associated with mean daily or cumulative doses of recombinant human growth hormone for any of the risk groups. Cause-specific mortality from diseases of the circulatory and haematological systems was increased in all risk groups.
In this cohort, the largest, to our knowledge, with long-term follow-up of patients treated with recombinant human growth hormone during childhood, all-cause mortality was associated with underlying diagnosis. In patients with isolated growth hormone deficiency or idiopathic short stature, recombinant human growth hormone treatment was not associated with increased all-cause mortality. However, mortality from certain causes was increased, emphasising the need for further long-term surveillance.
European Union.
重组人生长激素已应用 30 余年，其适应证已在全球范围内扩大。人们担心这种治疗可能会增加死亡率，但已发表的数据很少。我们报告了整个欧洲生长激素治疗安全性和适宜性（SAGhE）研究协作组的所有 8 个国家的数据，目的是研究儿童期接受重组人生长激素治疗的年轻成年患者的长期全因和死因特异性死亡率，并将其与潜在诊断相关联。
这项队列研究在 8 个欧洲国家（比利时、法国、德国、意大利、荷兰、瑞典、瑞士和英国）进行。根据患者的基础疾病预先评估治疗前的预期死亡率，并进行死因特异性死亡率随访。利用死亡风险的人年数和一般人群数据的预期发生率计算标准化死亡率比（SMR）。
该队列包括 24232 名儿童期接受重组人生长激素治疗的患者，随访时间超过 40 万患者年。在低危的孤立性生长激素缺乏症或特发性身材矮小症患者中，全因死亡率没有显著增加（SMR 1.1，95%CI 0.9-1.3）。在出生体重小于胎龄的儿童中，所有国家的全因死亡率均显著增加（SMR 1.5，1.1-1.9），但这一结果是由法国亚组驱动的。在中危或高危患者中，死亡率增加（SMR 3.8，3.3-4.4；和 17.1，15.6-18.7）。对于任何风险组，重组人生长激素的平均日剂量或累积剂量与死亡率均无关联。在所有风险组中，循环和血液系统疾病的死因特异性死亡率均增加。
在这项我们所知的最大的、对儿童期接受重组人生长激素治疗的患者进行长期随访的队列研究中，全因死亡率与基础诊断相关。在孤立性生长激素缺乏症或特发性身材矮小症患者中，重组人生长激素治疗与全因死亡率增加无关。然而，某些原因导致的死亡率增加，强调需要进一步进行长期监测。
欧盟。
