Safety And Efficacy Of Converting Patients With Acromegaly From Long-Acting Octreotide To Pegvisomant
WM Drake1, SV Rowles2, AN Paisley2, PM Stewart3, JP Monson1 & PJ Trainer2
We report the efficacy, safety, and effects on glucose homeostasis of converting patients with acromegaly from slow release octreotide (OT, treated for >3 months) to pegvisomant (Peg), a GH receptor antagonist. 52 patients (median age 49, range 23-81, 13 with diabetes) who had previously participated in a Peg clinical trial and subsequently treated with OT were enrolled in a 32-week, open-label, multicentre study. Peg 10 mg/d was started 4 weeks after the last dose of OT (week 0) and increased/decreased by 5 mg/d at weeks 12, 20 and 28, based on monthly serum IGF-I levels (Nichols acid extraction). Assessments (at weeks 4 and 32) included: signs and symptom score (SSS), ring size, fasting plasma glucose (FPG), HbA1c, insulin, and oral glucose tolerance test (oGTT). During treatment with Peg (mean dose 16 mg/day), serum IGF-I normalized in 85% of patients compared to 46% with a normal IGF-I on OT at week 0. Normalization of IGF-I was paralleled by improvement in the SSS. Median FPG decreased significantly with Peg in patients with and without diabetes (week 4 7.4 v 4.9 mmol/l week 32, P=0.0015; and 5.6 to 4.6 mmol/l, P<0.0001 respectively); as did HbA1c (7.1% v 6.3%, P=0.0068 with diabetes; 5.8% v 5.4%, P<0.0001 without diabetes). In patients without diabetes, mean glucose AUC on oGTT was significantly lower at week 32 v 4 (1284.4 v 1510.8 mmol.h/L, P=0.0001). In the 15 patients with a normal serum IGF-I on OT, mean FPG (-1.4 mmol/L; P=0.006) and HbA1c (-0.2%; P=0.09) improved with Peg, without any additional reduction in IGF-I. In summary, converting patients from OT to Peg with no washout period was safe and Peg was effective in normalizing IGF-I. Peg appears to improve glucose homeostasis in patients with acromegaly, with or without diabetes. This may influence choice of therapy for an individual patient.