Related Experiment Videos
A Canadian multi-centre, open-label long-term study of Pegvisomant treatment in refractory acromegaly
Shereen Ezzat1, Rania Gaspo, Omar Serri
1University of Toronto, Mount Sinai Hospital, Toronto, ON, M5G 1X5. sezzat@mtsinai.on.ca
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 insulin-like 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 Questionnaire. 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 long-term safety and efficacy of the GH receptor antagonist pegvisomant in achieving IGF-I control in patients with refractory acromegaly.
Insights
Pegvisomant, a growth hormone receptor antagonist, effectively normalized insulin-like growth factor I (IGF-I) in patients with refractory acromegaly. This treatment demonstrated long-term safety and efficacy, improving symptoms without tumor progression.
Area of Science:
- Endocrinology
- Pharmacology
Background:
- Acromegaly, a rare disorder, presents significant health risks including heart disease and reduced survival.
- Diagnosis is often delayed, with many patients presenting with invasive adenomas unsuitable for complete surgical removal.
- Standard treatments like somatostatin analogues may not always achieve optimal growth hormone (GH) and insulin-like growth factor I (IGF-I) normalization.
Purpose of the Study:
- To evaluate the long-term safety and efficacy of pegvisomant, a GH receptor antagonist, in patients with refractory acromegaly.
- To assess the ability of pegvisomant to normalize IGF-I levels in a Canadian multi-center study.
Main Methods:
- An open-label, dose-titrated, long-term study involving 19 adult patients with refractory acromegaly.
- Daily subcutaneous injections of pegvisomant were administered, with dosage adjusted based on IGF-I levels.
- Safety, IGF-I levels, and acromegaly symptoms were monitored regularly over the study period.
Main Results:
- Pegvisomant achieved age-adjusted normalization of IGF-I in nearly all patients, with sustained control over 27 months.
- IGF-I normalization correlated with measurable improvements in disease symptoms.
- No radiographic evidence of pituitary tumor progression was observed, and the safety profile was deemed satisfactory for long-term use.
Conclusions:
- Pegvisomant is a safe and effective treatment for achieving IGF-I control in patients with refractory acromegaly.
- The study supports the long-term use of pegvisomant for managing this challenging condition.
Related Concept Videos
02:56Treatment Resistent Cancers
02:56Treatment Resistant Cancers