BACKGROUND: Normalization of IGF-I in patients with acromegaly is associated with
a decrease in mortality. Pegvisomant may be more effective in lowering IGF-I than
octreotide.
SUBJECTS AND METHODS: The efficacy and safety of pegvisomant and octreotide
long-acting release (LAR) were compared in 118 patients with acromegaly in this
52-week, multicenter, open-label, randomized study. The primary endpoint was
IGF-I normalization at week 52. Secondary endpoints included mean changes from
baseline in IGF-I, IGF binding protein 3, acromegaly signs and symptom scores,
ring size, acromegaly quality of life questionnaire scores, and safety.
RESULTS: Fifty-six patients received pegvisomant and 57 received octreotide LAR.
IGF-I normalized in 51% of pegvisomant patients and 34% treated with octreotide
LAR (p=0.09, ns). Patients with baseline IGF-I > or = 2x upper limit of normal
had a higher rate of IGF-I normalization with pegvisomant vs octreotide LAR
(p=0.05). Among the patients who did not achieve a normalized IGF-I,
pegvisomant-treated patients were more likely to be receiving < 30 mg of study
drug (71% vs 16%). Treatment-related adverse events were mild-to-moderate in both
groups. Mean fasting glucose decreased in diabetic and non-diabetic patients on
pegvisomant whereas octreotide LAR was associated with an increase at week 52
(p=0.005 and p=0.003 between groups, respectively). Mean change in tumor volume
during treatment was similar between groups.
CONCLUSIONS: Pegvisomant and octreotide LAR were equally effective in normalizing
IGF-I in the overall population, and pegvisomant was more effective in patients
with higher baseline IGF-I levels. Pegvisomant had a more favorable effect on
parameters of glycemic control