A randomized, controlled, multicentre trial comparing pegvisomant alone with combination therapy of pegvisomant and long-acting octreotide in patients with acromegaly.
OBJECTIVE
For patients with acromegaly who are suboptimally controlled on long-acting octreotide (LAR), treatment options are to switch to pegvisomant monotherapy (PM) or add pegvisomant to LAR (P-LAR). Our objective was to evaluate if the safety and efficacy of these regimens differ.


METHODS
This was an open-label, multicentre, randomized, 40-week outpatient study. The control arm consisted of patients controlled on LAR (n = 28).


METHODS
A total of 27 patients with suboptimally controlled acromegaly [as indicated by a serum IGF-I level > or = 1.3 x upper limit of normal (ULN) of the age-related reference range] were randomized to PM (10 mg once daily initially, then adjusted in 5-mg increments every 8 weeks based on IGF-I levels) and 29 to P-LAR (LAR dosing remained fixed).


METHODS
The primary end-point was adverse events (AEs). The secondary end-point was biochemical IGF-I-based efficacy. The RIA for IGF-I was discontinued by the manufacturer during the study and a chemiluminescent assay was subsequently used. Previously obtained IGF-I levels were re-analysed.


RESULTS
PM and P-LAR were well tolerated and there were no differences in the number of AEs. Patients receiving P-LAR tended to be more likely to have clinically significant increases in hepatic transaminase levels, especially those receiving high-dose LAR. Normalization of IGF-I was similar with both regimens (56% and 62% of patients for PM and P-LAR respectively). The change in IGF-I assay resulted in lower rates of IGF-I normalization than expected. Reductions in fasting glucose levels were greater with PM than with P-LAR (-0.8 mmol/l; 95% confidence interval -1.16, -0.53 mmol/l).


CONCLUSIONS
In patients suboptimally controlled on LAR, PM and P-LAR were equally well tolerated and effective in normalizing IGF-I, and overall clinical improvement was observed with both regimens. Thus, pegvisomant monotherapy and adjunctive therapy are equally viable options for the treatment of LAR-resistant acromegaly.
Department of Endocrinology, Christie Hospital, Wilmslow Road, Manchester, UK. Peter.Trainer@manchester.ac.uk
Peter J
PJ
Trainer
Shereen
S
Ezzat
Gwyn A
GA
D'Souza
Gary
G
Layton
Christian J
CJ
Strasburger
D000172:Acromegaly / Q000188:drug therapy*; D000328:Adult; D003692:Delayed-Action Preparations; D004359:Drug Therapy, Combination; D005260:Female; D019382:Human Growth Hormone / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008099:Liver / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D015282:Octreotide / Q000008:administration & dosage* / Q000009:adverse effects
D003692:Delayed-Action Preparations; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; C406545:pegvisomant; D015282:Octreotide