Experience with pegvisomant treatment in acromegaly in a single Brazilian tertiary reference center: efficacy, safety and predictors of response

Abstract

Objective: To describe the safety and efficacy of pegvisomant therapy and the predictors of treatment response in acromegaly patients at a single tertiary reference center in Brazil. Materials and methods: We retrospectively reviewed the clinical, hormonal and radiological data of acromegaly patients treated with pegvisomant in our center. We also evaluated the presence of the d3 isoform of the growth hormone receptor (d3GHR). Results: Twenty-seven patients were included (17 women). Pegvisomant was used in combination with octreotide LAR in 20 patients (74%), in combination with cabergoline in one (4%) and as monotherapy in six (22%). IGF-I normalization was achieved in 23 patients (85%). Mild and transitory elevation of liver enzymes was observed in two patients (7.4%), tumor growth in one (3.4%) and lipodystrophy in two (7.4%). One patient stopped the drug due to headaches. The GHR isoforms were evaluated in 14 patients, and the presence of at least one d3GHR allele was observed in 43% of them, but it was not a predictor of treatment response. Only pretreatment IGF-I level was a predictor of treatment response. Conclusion: Pegvisomant treatment was highly effective and safe in our series of Brazilian patients. A better chance of disease control can be expected in those with lower pre-pegvisomant IGF-I levels. Arch Endocrinol Metab. 2016;60(5):479-85

Pegvisomant in acromegaly: a multicenter real-life study in Argentina

“…Regarding the safety of PEGV, we found that the increase in liver enzymes associated with the use of PEGV was 9%, similar to 7.7% and 7.4% reported by the French and Brazilian groups, respectively (29,32). Other investigators reported higher rate of hepatotoxicity for combined treatment with SRL (30).…”

“…Recently, a Brazilian study (29) published the findings from a series of 27 patients retrospectively evaluated, reporting 85% normalization of IGF-1 under PEGV treatment. The authors attribute this high rate of effectiveness to the fact that they are tertiary reference center with high experience in treating acromegaly and therefore, patients have a more appropriate dose adjustment to attain the goals of disease control.…”

Treatment escape reduces the effectiveness of cabergoline during long‐term treatment of acromegaly in monotherapy or in association with first‐generation somatostatin receptor ligands

“…26,27 The control rates with pegvisomant are also higher, being more than 90% in clinical trials and 63% in a large databank of real-life treatment. [28][29][30][31] Therefore, the control rate we found with CAB is lower than that observed with other medical treatments in acromegaly. 26,27,30,32 It is important to highlight that the control rate observed in our study probably overestimates the efficacy of CAB in monotherapy, as in our centre, only patients with less severe disease tend to be selected for CAB treatment in monotherapy.…”

“…The control rate with SRL is approximately 40% in prospective studies and can be higher than 60% including retrospective studies . The control rates with pegvisomant are also higher, being more than 90% in clinical trials and 63% in a large databank of real‐life treatment . Therefore, the control rate we found with CAB is lower than that observed with other medical treatments in acromegaly …”

MECHANISMS IN ENDOCRINOLOGY: Lessons from growth hormone receptor gene-disrupted mice: are there benefits of endocrine defects?

“…Later studies from Korea (234) and Turkey (235) have reported higher BMIs in d3-GHR polymorphic acromegaly patients as the only consistent difference due to this particular GHR isoform. Interesting, the d3-GHR isoform was not found to be a determinant in response to Pegvisomant treatment in acromegaly patients (236). The d3-GHR isoform and its sexually dimorphic phenotypes provide an additional opportunity of dissecting the nature of association of the GH/IGF axis in determining lifespan.…”