Experience from the Argentine Pegvisomant Observational Study: Preliminary Data

Abstract

The GH receptor antagonist pegvisomant is an efficient agent to achieve biochemical control of acromegaly in those cases refractory to surgery and medical therapy with somatostatin analogs. We conducted an observational multicenter study consisting of data collection in accordance with the standard management of patients with acromegaly in everyday practice. We reviewed the medical records of 28 patients, 23 females, who were treated with pegvisomant due to the lack of biochemical response or intolerance to the somatostatin analogs. The objective was to monitor long-term safety and efficacy of the antagonist. 82% of the patients had previous pituitary surgery, 53.6% radiotherapy and 96.4% received medical therapy for acromegaly. Only 19.2% of the patients had pituitary residual tumor size larger than 1 cm, the remainder harbored a microadenoma or no visible tumor in the pituitary images. In terms of biochemical efficacy, IGF-I levels decreased to normal ranges in 45% and 58.8% of patients after 3 and 6 months of treatment, respectively, the daily mean dose of pegvisomant being 9.6+/-1.1 mg. Adverse events, potentially related to pegvisomant were reported in 6 patients (21.4%), local injection site reaction and elevated liver enzymes being the most frequent. Tumor size did not show enlargement in the evaluated population (15 patients) during the period of the study. This paper presents preliminary data from a small observational study in Argentina which represents the first database in our country.

Does pegvisomant treatment expertise improve control of resistant acromegaly? The Italian ACROSTUDY experience

“…The lack of data concerning radiotherapy is a limit of our study. On the other hand, it is note of worthy that 72 % of patients in group B achieved normal IGF-1 levels at the last visit, a figure perfectly in line with other clinical studies [8][9][10][11][12]. On the contrary, only 57 % of group A showed disease control at last visit, a disappointing result probably justified by an inadequate patients' selection, by insufficient pegvisomant doses or by the enrollment in group A of younger patients with a more aggressive disease.…”

“…Drug effectiveness varies widely from one study to another, ranging 59-100 % [3][4][5][6][7][8][9][10][11]. Inadequate dose titration, poor compliance to daily injections, suboptimal selection of patients, and some problems related to IGF-1 measurement could justify a lowerthan-expected efficacy although this phenomenon has neither been appropriately investigated nor well explained until now.…”

“…However, more recent noninterventional studies performed in the clinical setting have shown that the percentage of patients who obtain adequate disease control is lower, ranging from 60 to 87 % [8][9][10][11][12]. In 2004, a global noninterventional safety surveillance study of long-term treatment with pegvisomant, named ACROS-TUDY, was activated in several countries.…”

Expert consensus document: A consensus on the medical treatment of acromegaly

“…34 A discrepancy exists between the proportion of patients achieving normal IGF-I levels during treatment with pegvisomant in randomized controlled trials and community-based databases, suggesting differences in participant selection, dose titration, patient compliance, history of earlier irradiation, and occurrence of adverse events (LQ). 33,[35][36][37] If long-term control of acromegaly is achieved with pegvisomant, down-titration of the dose or decreasing the frequency of administration might be possible (DR).…”

Pegvisomant in acromegaly: an update

“…Accordingly, PEG starting dose should be higher and dose titration more rapid in younger patients, in the obese subjects and in those with a worse endocrine profile [31, 32]. Previous studies also showed that IGF-I normalization requires lower doses in male than in female patients, and in irradiated compared to non-irradiated cases [17, 26, 33]. On the other hand, an appropriate PEG dose titration up to the maximum allowed dosage was shown to normalize IGF-I levels in up to 90% of cases, even in the real life setting [34].…”