Endocrine Abstracts

Two medical therapies are now available for the treatment of acromegaly. Pegvisomant is a growth hormone (GH) receptor antagonist. Somatostatin analogues, in contrast, act by inhibiting the release of GH from the pituitary. The primary objective of this study was to compare the efficacy of pegvisomant (P) to that of octreotide LAR (LAR) in terms of IGF-1 normalisation. The secondary objective was to compare safety and tolerability between the two treatments.

The study was a 52 week, multi-centre, open label, parallel group, randomised trial in acromegalic subjects who were either de novo, or post-surgical, with IGF-1 levels ≥ 1.3× upper limit of normal (ULN). Subjects were randomised to either P or LAR, using stratification with respect to baseline severity (mild (IGF-1 ≥1.3 ULN; severe (IGF-1 ≥ 2× ULN), The dose of P was started at 10 mg sc and titrated at 8 week intervals to normalise IGF-1 up to a maximum of 40 mg. The dose of octreotide was 50 μg sc three times daily, switching at 4 weeks to 20 mg LAR im monthly. The dose was titrated to normalise IGF-1 at 16 week intervals up to a maximum of 30 or 40 mg monthly, according to local practice. During the study, the Nichols IGF-1 radioimmunoassay (RIA) became unavailable and analysis was switched to the Immulite chemiluminescent assay. The difference in number of subjects who achieved IGF-1 normalisation (responders (R)) between the two treatment groups was analysed by Fisher’s Exact test, while changes from baseline in efficacy parameters were analysed by ANCOVA. The R rate was higher in the P group compared to LAR, but the difference was not statistically significant. In P, R rates using the Immulite and RIA assays respectively were 51%, 83%, compared to 34% and 67% in LAR. The number of subjects with treatment-related adverse events was 21 in P and 29 in LAR. Four subjects in both groups had abnormal (≥ 3x ULN ≤10×) hepatic transaminases. There was a higher incidence of biliary tract abnormalities with LAR.Treatment with P was at least as efficacious as LAR. It is hypothesised that the lower than expected R rates and non-significant difference in IGF-1 normalisation between the 2 treatment groups are due to a change in assay methodology and non-optimal dose titration with P.