Wüster C, Melchinger U, Eversmann T, Hensen J, Kann P, von zur Mühlen A, Ranke M B, Schmeil H, Steinkamp H, Tuschy U
Abteilung Innere Medizin I, Universität Heidelberg.
Med Klin (Munich). 1998 Oct 15;93(10):585-91. doi: 10.1007/BF03042673.
Substitution of pituitary insufficient patients with recombinant human growth hormone (rhGH) in addition to the conventional substitution with glucocorticoids, L-thyroxine and sex hormones has been approved by the regulatory authorities in 1995 with the imposition to conduct surveillance studies to monitor drug safety.
24% of all patients were within their 2nd treatment year, 15% within their 4th year, maximum treatment period was 6 years. There were 2 peaks within the patients age distribution: 30 to 39 years (24%) and 50 to 59 years (24%). The causes for pituitary disease were as follows: pituitary adenomas (47%), idiopathic (16%), craniopharyngeomas (16%) and others (21%). Mean GH dose was 1.5 IU/d s.c. (range 0.4 to 4 IU/d). Serum-IGF-1 increased by 159 and 192% in females and males. Waist circumference decreased by 2% and serum cholesterol was lowered by 5.5% in males. There were 2 cases with new carcinomas, 1 diabetes mellitus II and 1 death. Adverse events (AEs) within KIMS were compared to those of the treatment (GH) and placebo (PI) groups of the previous admission trials (in percent): edema: KIMS 10, GH 37, Pl 3; arthralgia: KIMS 8, GH 19, Pl 2; muscle pain: KIMS 3, GH 16, Pl 3; dizziness: KIMS 2, GH 1, Pl 3; headache: KIMS 2, GH 3, Pl 2; others: KIMS 2, GH 22, Pl 13. The reported incidence of AEs in KIMS was lower than in previous clinical trials. There might be 3 reasons for this: 1. under-reporting, particularly those AEs not likely to be related to GH treatment; 2. doses used in trials were 2-fold higher than in KIMS; 3. dose titration for individual patients.
Surveillance programs are important for monitoring of drug long-term efficacy and safety.
1995年，监管部门批准垂体功能不全患者在常规使用糖皮质激素、左甲状腺素和性激素替代治疗的基础上，加用重组人生长激素（rhGH），并要求开展监测研究以监测药物安全性。
所有患者中，24%处于治疗第2年，15%处于第4年，最长治疗期为6年。患者年龄分布有两个高峰：30至39岁（24%）和50至59岁（24%）。垂体疾病的病因如下：垂体腺瘤（47%）、特发性（16%）、颅咽管瘤（16%）和其他（21%）。平均生长激素剂量为1.5 IU/d皮下注射（范围为0.4至4 IU/d）。女性和男性的血清胰岛素样生长因子-1分别升高了159%和192%。男性腰围下降了2%，血清胆固醇降低了5.5%。有2例新发癌症、1例II型糖尿病和1例死亡。将国际多中心生长激素治疗监测研究（KIMS）中的不良事件与之前入院试验的治疗（生长激素）组和安慰剂（PI）组的不良事件进行比较（以百分比计）：水肿：KIMS为10%，生长激素组为37%，安慰剂组为3%；关节痛：KIMS为8%，生长激素组为19%，安慰剂组为2%；肌肉疼痛：KIMS为3%，生长激素组为16%，安慰剂组为3%；头晕：KIMS为2%，生长激素组为1%，安慰剂组为3%；头痛：KIMS为2%，生长激素组为3%，安慰剂组为2%；其他：KIMS为2%，生长激素组为22%，安慰剂组为13%。KIMS中报告的不良事件发生率低于之前的临床试验。可能有3个原因：1. 报告不足，尤其是那些不太可能与生长激素治疗相关的不良事件；2. 试验中使用的剂量比KIMS中的高2倍；3. 对个体患者进行剂量滴定。
监测项目对于监测药物的长期疗效和安全性很重要。
