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. Design This was an open-label, multicentre, randomized, 40-week outpatient study. The control arm consisted of patients controlled on LAR (n = 28). Patients A total of 27 patients with suboptimally controlled acromegaly [as indicated by a serum IGF-I level ≥ 1·3 × 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). Measurements 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. © 2009 Blackwell Publishing Ltd.