Università Federico II di Napoli, Naples, Italy.
University of São Paulo Medical School, São Paulo, Brazil.
Eur J Endocrinol. 2020 Jun;182(6):583. doi: 10.1530/EJE-19-0762.
In the Phase III PAOLA study (clinicaltrials.gov: NCT01137682), enrolled patients had uncontrolled acromegaly despite ≥6 months of octreotide/lanreotide treatment before study start. More patients achieved biochemical control with long-acting pasireotide versus continued treatment with octreotide/lanreotide (active control) at month 6. The current work assessed the extent of comorbidities at baseline and outcomes during a long-term extension.
DESIGN/METHODS: Patients receiving pasireotide 40 or 60 mg at core study end could continue on the same dose in an extension phase if biochemically controlled or receive pasireotide 60 mg if uncontrolled. Uncontrolled patients on active control were switched to pasireotide 40 mg, with the dose increased at week 16 of the extension if still uncontrolled (crossover group). Efficacy and safety are reported to 304 weeks (~5.8 years) for patients randomized to pasireotide (core + extension), and 268 weeks for patients in the crossover group (extension only).
Almost half (49.5%; 98/198) of patients had ≥3 comorbidities at core baseline. During the extension, 173 patients received pasireotide. Pasireotide effectively and consistently reduced GH and IGF-I levels for up to 5.8 years' treatment; 37.0% of patients achieved GH <1.0 µg/L and normal IGF-I at some point during the core or extension. Improvements were observed in key symptoms. The long-term safety profile was similar to that in the core study; 23/173 patients discontinued treatment because of adverse events.
In this patient population with a high burden of comorbid illness, pasireotide was well tolerated and efficacious, providing prolonged maintenance of biochemical control and improving symptoms.
在 III 期 PAOLA 研究（clinicaltrials.gov：NCT01137682）中，纳入的患者在研究开始前接受奥曲肽/兰瑞肽治疗至少 6 个月后仍存在未控制的肢端肥大症。与继续使用奥曲肽/兰瑞肽（活性对照）相比，更多患者在第 6 个月时实现了生化控制。目前的工作评估了基线时合并症的程度以及长期扩展期间的结果。
设计/方法：核心研究结束时接受帕瑞肽 40 或 60mg 治疗的患者，如果生化控制良好，可以在扩展阶段继续使用相同剂量，如果控制不佳，则可以使用帕瑞肽 60mg。活性对照的未控制患者转换为帕瑞肽 40mg，如果仍未控制，则在扩展阶段的第 16 周增加剂量（交叉组）。报告了接受帕瑞肽（核心+扩展）随机分组的患者至 304 周（约 5.8 年）和接受交叉组（仅扩展）的患者至 268 周的疗效和安全性。
在核心基线时，近一半（49.5%；98/198）的患者存在≥3 种合并症。在扩展期间，173 名患者接受了帕瑞肽治疗。帕瑞肽在长达 5.8 年的治疗中有效地持续降低了 GH 和 IGF-I 水平；37.0%的患者在核心或扩展期间的某个时间点达到了 GH<1.0μg/L 和正常 IGF-I。关键症状得到了改善。长期安全性与核心研究相似；23/173 名患者因不良反应而停止治疗。
在患有高合并症负担的患者人群中，帕瑞肽具有良好的耐受性和疗效，提供了生化控制的长期维持，并改善了症状。
