Brazilian multicenter study on pegvisomant treatment in acromegaly

Abstract

Objective: Investigate the therapeutic response of acromegaly patients to pegvisomant (PEGV) in a real-life, Brazilian multicenter study.

Subjects and methods: Characteristics of acromegaly patients treated with PEGV were reviewed at diagnosis, just before and during treatment. All patients with at least two IGF-I measurements on PEGV were included. Efficacy was defined as any normal IGF-I measurement during treatment. Safety data were reviewed. Predictors of response were determined by comparing controlled versus uncontrolled patients.

Results: 109 patients [61 women; median age at diagnosis 34 years; 95.3% macroadenomas] from 10 Brazilian centers were studied. Previous treatment included surgery (89%), radiotherapy (34%), somatostatin receptor ligands (99%), and cabergoline (67%). Before PEGV, median levels of GH, IGF-I and IGF-I % of upper limit of normal were 4.3 µg/L, 613 ng/mL, and 209%, respectively. Pre-diabetes/diabetes was present in 48.6% and tumor remnant in 71% of patients. Initial dose was 10 mg/day in all except 4 cases, maximum dose was 30 mg/day, and median exposure time was 30.5 months. PEGV was used as monotherapy in 11% of cases. Normal IGF-I levels was obtained in 74.1% of patients. Glycemic control improved in 56.6% of patients with pre-diabetes/diabetes. Exposure time, pre-treatment GH and IGF-I levels were predictors of response. Tumor enlargement occurred in 6.5% and elevation of liver enzymes in 9.2%. PEGV was discontinued in 6 patients and 3 deaths unrelated to the drug were reported.

Conclusions: In a real-life scenario, PEGV is a highly effective and safe treatment for acromegaly patients not controlled with other therapies.

Figure 1. Individual IGF-I levels, expressed as a percentage of the age-adjusted upper limit of normal (ULN) range, before (dark blue circles) and after (light blue circles) pegvisomant (PEGV) treatment in 109 Brazilian patients with acromegaly.

Figure 2. IGF-I levels at diagnosis, just before pegvisomant treatment (PEGV-OFF) and nadir values after pegvisomant treatment (PEGV-ON) in 109 Brazilian patients with acromegaly. Horizontal lines in the box plots represent from top to bottom: 97, 75, median, 25, and 3 percentiles, and the dots represent mean values.