Turner Helen E, Thornton-Jones Viv A, Wass John A H
Department of Endocrinology, Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, UK.
Clin Endocrinol (Oxf). 2004 Aug;61(2):224-31. doi: 10.1111/j.1365-2265.2004.02084.x.
The depot long-acting somatostatin analogue octreotide LAR (LAR) provides effective and well-tolerated treatment for acromegaly. Despite a 4-weekly recommended injection frequency, prolonged duration of GH suppression has been observed in some patients following treatment with long-acting somatostatin analogues. The aim of our study was to perform a prospective systematic study to determine whether extending the interval between doses of LAR allows maintenance of 'safe' GH in selected patients with acromegaly.
Twenty-two patients (15 men, seven women), mean age 58.9 years (35-81 years) with active acromegaly (mGH > 5 mU/l), requiring treatment were selected to receive treatment with LAR. Eleven patients had received previous treatment with both transsphenoidal surgery and radiotherapy, while six had received surgery alone. All patients were commenced on treatment with 20 mg LAR intramuscularly (i.m.) every 4 weeks. Mean GH (mGH) was measured after three consecutive injections immediately prior to the fourth injection. The dose frequency was systematically reduced after every four injections if mGH < 5 mU/l. Once mGH > 5 mU/l, the dose frequency was increased and mGH reassessed.
The dosing interval was successfully increased to greater than 4 weeks in 20/22 patients (90.9%). Six of 22 (27.3%) were receiving injections every 8 weeks and 3/22 (13.6%) every 12 weeks. GH and IGF-I were lower on treatment compared with baseline (P < 0.01). There was no difference in individual mGH and IGF-I between the values on 4-weekly dosing and those at final dose frequency. There was no relationship between final dose frequency and either mean GH or IGF-I prior to LAR, patient age, or previous treatment. The percentage suppression following 100 micro g octreotide subcutaneously did not predict subsequent dose frequency of LAR. The drug cost if patients had continued at 4-weekly intervals would be UK pound 187 850, compared with UK pound 101 065 for the individually titrated dose frequency (P < 0.01). This represents a final cost of 53.8% of the 4-weekly injection price.
Individual tailoring of LAR administration maintains control of acromegaly, with reduced injection frequency and improved cost-effectiveness.
长效生长抑素类似物奥曲肽长效注射剂(LAR)为肢端肥大症提供了有效且耐受性良好的治疗方法。尽管推荐每4周注射一次,但在一些接受长效生长抑素类似物治疗的患者中观察到生长激素(GH)抑制持续时间延长。我们研究的目的是进行一项前瞻性系统研究,以确定延长LAR给药间隔是否能使部分肢端肥大症患者维持“安全”的GH水平。
选择22例(15例男性,7例女性)平均年龄58.9岁(35 - 81岁)的活动性肢端肥大症患者(平均GH[mGH]>5 mU/L)接受LAR治疗。11例患者曾接受经蝶窦手术和放疗,6例仅接受过手术。所有患者开始每4周肌肉注射(i.m.)20 mg LAR进行治疗。在第四次注射前连续三次注射后测量平均GH(mGH)。如果mGH<5 mU/L,每四次注射后系统地减少给药频率。一旦mGH>5 mU/L,增加给药频率并重新评估mGH。
22例患者中有20例(90.9%)成功将给药间隔延长至大于4周。22例中有6例(27.3%)每8周注射一次,3/22例(13.6%)每12周注射一次。与基线相比,治疗期间GH和胰岛素样生长因子-I(IGF-I)降低(P<0.01)。每4周给药时的个体mGH和IGF-I值与最终给药频率时的值之间无差异。最终给药频率与LAR治疗前的平均GH或IGF-I、患者年龄或既往治疗均无关系。皮下注射100 μg奥曲肽后的抑制百分比不能预测LAR随后的给药频率。如果患者继续每4周给药一次,药物费用将为187850英镑,而个体化调整给药频率的费用为101065英镑(P<0.01)。这相当于每4周注射价格的最终费用的53.8%。
LAR给药的个体化调整可维持对肢端肥大症的控制,减少注射频率并提高成本效益。