A Canadian multi-centre, open-label long-term study of Pegvisomant treatment in refractory acromegaly

Ezzat, Shereen; Gaspo, Rania; Serri, Omar; Ur, Ehud; Chik, Constance L.
December 2009
Clinical & Investigative Medicine;Dec2009, Vol. 32 Issue 6, pE265
Academic Journal
Purpose: Acromegaly is a rarely diagnosed condition with potentially serious complications including accelerated heart disease and reduced survival. After a mean interval of nearly 9 years from onset of disease, a significant proportion of patients are diagnosed with invasive adenomas precluding complete surgical resection. Furthermore, strict normalization of the growth hormone (GH) target insulinlike growth factor I (IGF-I) cannot always be achieved by adjunctive medical therapy with somatostatin analogues. Here we report the results of a Canadian multi-centre study open-label, dose-titrated long-term study examining safety and efficacy outcomes of a growth hormone receptor antagonist, pegvisomant in 19 patients with refractory acromegaly. Methods: Previously pegvisomant-treated and treatment naïve refractory acromegalic patients at least 18 yr of age were eligible (n=19). Patients received open-label daily subcutaneous injections of pegvisomant adjusted according to IGF-I levels. Safety and IGF-I levels were assessed every 4 to 6 wk. Baseline and follow-up visits at 3-month intervals also included administration of the Signs and Symptoms of Acromegaly uestionnaire. This study is registered with ClinicalTrials.gov, NCT00151437. Results: We show that, in escalating doses, pegvisomant results in age-adjusted normalization of IGF-I in nearly all such patients. This IGF-I normalization occurred early on and was maintained throughout the study period of 27 months (IGF-I standard deviation score (SDS), mean ± SE: 1.66 ± 0.36, P=0.0003 vs baseline), with a nadir at 18 months (IGF-I SDS, mean ± SE: 1.50 ± 0.38, P=0.0010 vs baseline). IGF-I control was also accompanied by measurable improvements in disease-associated symptoms and without radiographic evidence of pituitary tumour progression. Overall, the safety profile of pegvisomant therapy in this patient population was found to be satisfactory and suitable for a long-term treatment. Conclusion: Our findings provide support for the longterm safety and efficacy of the GH receptor antagonist pegvisomant in achieving IGF-I control in patients with refractory acromegaly.


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