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A randomized, controlled, multicentre trial comparing pegvisomant alone with combination therapy of pegvisomant and long‐acting octreotide in patients with acromegaly
Author(s) -
Trainer Peter J.,
Ezzat Shereen,
D’Souza Gwyn A.,
Layton Gary,
Strasburger Christian J.
Publication year - 2009
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/j.1365-2265.2009.03620.x
Subject(s) - pegvisomant , medicine , acromegaly , adverse effect , octreotide , randomized controlled trial , gastroenterology , somatostatin , endocrinology , growth hormone , hormone
Summary 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.