Treatment of acromegaly with pegvisomant in clinical practice

The German Pegvisomant Observational Study is at present the largest database of patients with acromegaly (n=229) treated with pegvisomant (Somavert). 90.4% pts underwent pituitary surgery, 43.2% received radiation therapy, and previous medical therapy included dopamine agonists (48.1%), octreotide (89.1%) and/or lanreotide (10%). Most relevant concomitant diseases at baseline were gallstone disease (24.4%), diabetes mellitus (28.9%) and heart failure (10.0%). Efficacy analysis was performed in 177 pts with a follow-up after 6 months, in 128 pts after 12 months and in 61 pts after 2yrs. Mean duration of treatment was 51.8±35.8 wks. IGF-I was normalized in 64.4% at 6 months with a median dose of 15.0mg/d and in 76.3% of pts treated for at least 2yrs. IGF-I levels expressed in relation to the individual reference rage decreased from 1.75±0.91 fold at baseline to 1.05±0.62 after 6 months and to 0.89±0.41 after 2yrs. Fasting glucose levels improved significantly from 150±68mg/dl to 119±46mg/dl after 12 months and 104±21mg/ml after 24 months, respectively. Additionally, antidiabetic medication of these patients could be reduced. Elevated liver function tests (LFTs) >3 times above normal occurred in 12 pts receiving octreotide before. In 7/12 pts LFTs spontaneously normalized during continued treatment. In all other pts levels normalized after discontinuation. ALT was the enzyme most prominently elevated with exception of 2 pts and elevation occurred dose independently. Progression of remnant pituitary adenoma was reported in a total of 12 pts. All cases were re-evaluated by a blinded investigator. In 5 pts tumor progression could not be verified at re-evaluation. In 3 pts, the tumor continuously grew on somatostatin analogues. 2 pts had a slight increase in tumor size without clinical relevance and 2 pts showed a tumor expansion after somatostatin treatment was stopped. In conclusion, Pegvisomant is well tolerated with a safety profile similar to that reported in clinical trials, and can effectively reduce IGF-I in pts refractory to conventional therapy.