The GH receptor antagonist pegvisomant entered clinical trials in 1997 and was (UK) marketed in 2005. There is little long-term experience with this novel drug. We report the experience from two centres that used common protocols to manage 58 patients (36 male, median age 53, range 27 78) since 1997. Before commencing pegvisomant, patients had IGF-I above the upper limit of normal (ULN) of age-related reference ranges (median 1.8 xULN, range 1.24.1 xULN) and were uncontrolled on other medical therapies. 74% had pituitary surgery, 86% radiotherapy.
Median duration of pegvisomant therapy was 18 months (range 291 (26 patients had >18mths treatment)), this was non-continuous in 28 patients. 88% normalised IGF-I using a median dose of 15 mg daily (range 10 mg alternate day −60 mg daily) with no influence of gender on dose requirement. Five patients had combination therapy, pegvisomant with somatostatin analogues (n=2)/ cabergoline (n=3). Two patients initially controlled on 10 mg and 20 mg required dose increases (to 20 mg+40 mg) over 24 months to reduce IGF-I. 12% were uncontrolled, these were undergoing dose titration or stopped treatment prior to control.
27 patients stopped pegvisomant. Reasons include death (n=3, drug unrelated), side effects (abnormal LFTs(n=3), headaches(n=2), arthralgia(n=1)), patient choice (n=6). 69% reported no side effects. 2 patients developed elevated liver transaminases within 1 month of starting which normalised on stopping pegvisomant. Patients had 6 - 12 monthly pituitary MRI scans. One patient had significant tumour size increase.
In conclusion, our long-term experience in 58 patients indicates pegvisomant to be effective, safe and well-tolerated. Raised transaminases occurred within the first month of therapy, and tumour growth was seen in one patient (tumour was growing prior to pegvisomant). In two patients increasing doses of pegvisomant were required to keep IGF-I within the target range.