Gender, Body Weight, Disease Activity, and Previous Radiotherapy Influence the Response to Pegvisomant

Parkinson, Craig; Burman, Pia; Messig, Michael; Trainer, Peter J

doi:10.1210/jc.2006-1412

Cited by 64 publications

(60 citation statements)

References 37 publications

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“…Published findings (40) in which pegvisomant doses required for an effective treatment depend on the patient's BMI support our results, in as much as the BMI is known to correlate with insulin levels.…”

Section: European Journal Of Endocrinologysupporting

confidence: 88%

Therapy of acromegalic patients exacerbated by concomitant type 2 diabetes requires higher pegvisomant doses to normalise IGF1 levels

Droste¹,

Domberg²,

Buchfelder

et al. 2014

European Journal of Endocrinology

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Objective: Acromegaly is associated with an increased prevalence of glucose metabolism disorders. Clinically confirmed diabetes mellitus is observed in approximately one quarter of all patients with acromegaly and is known to have a worse prognosis in these patients. Design: Of 514 acromegalic patients treated with pegvisomant and recorded in the German Cohort of ACROSTUDY, 147 had concomitant diabetes mellitus. We analysed these patients in an observational study and compared patients with and without concomitant diabetes. Results: Under treatment with pegvisomant, patients with diabetes mellitus rarely achieved normalisation (64% in the diabetic cohort vs 75% in the non-diabetic cohort, PZ0.04) for IGF1. Diabetic patients normalised for IGF1 required higher pegvisomant doses (18.9 vs 15.5 mg pegvisomant/day, P!0.01). Furthermore, those diabetic patients requiring insulin therapy showed a tendency towards requiring even higher pegvisomant doses to normalise IGF1 values than diabetic patients receiving only oral treatment (22.8 vs 17.2 mg pegvisomant/day, PZ0.11). Conclusions: Hence, notable interdependences between the acromegaly, the glucose metabolism of predisposed patients and their treatment with pegvisomant were observed. Our data support recent findings suggesting that intra-portal insulin levels determine the GH receptor expression in the liver underlined by the fact that patients with concomitant diabetes mellitus, in particular those receiving insulin therapy, require higher pegvisomant doses to normalise IGF1. It is therefore important to analyse various therapy modalities to find out whether they influence the associated diabetes mellitus and/or whether the presence of diabetes mellitus influences the treatment results of an acromegaly therapy.

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Section: European Journal Of Endocrinologysupporting

confidence: 88%

Therapy of acromegalic patients exacerbated by concomitant type 2 diabetes requires higher pegvisomant doses to normalise IGF1 levels

Droste¹,

Domberg²,

Buchfelder

et al. 2014

European Journal of Endocrinology

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“…There are few studies in the literature addressing predictors of response to pegvisomant treatment (23,24). One of the possible predictors is the presence of the d3GHR isoform of the GHR.…”

Section: Discussionmentioning

confidence: 99%

“…There are no robust predictors of the response to pegvisomant treatment, although pre-treatment GH and IGF-I levels, gender, body mass index, fat mass, presence of type 2 diabetes mellitus (DM), age and previous radiotherapy can influence the chance of disease control (23,24). Additionally, some studies evaluated the GHR polymorphisms as a possible cause of a lower response to the drug, with conflicting results regarding whether patients who present the exon-3 deleted GHR (d3GHR) had a better response to pegvisomant (25)(26)(27)(28).…”

Section: Introductionmentioning

confidence: 99%

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

Kasuki

Machado

Ogino

et al. 2016

Arch. Endocrinol. Metab.

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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

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“…It is known that radiotherapy minimally reduces the dose of pegV required to normalize IGF1 (12) and that radiotherapy continues to reduce GH levels for up to 15 years post-treatment. Therefore we cannot completely exclude that the ongoing effect of radiotherapy may have contributed to the sustained control of IGF1 on conversion to weekly dosing.…”

Section: Discussionmentioning

confidence: 99%

Successful use of weekly pegvisomant administration in patients with acromegaly

Higham

Thomas²,

Bidlingmaier³

et al. 2009

European Journal of Endocrinology

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Context: Clinical trials using 80 mg once weekly pegvisomant (pegV) in active acromegaly led to a 30% fall in serum IGF1. Subsequent studies demonstrated that daily administration of up to 40 mg/day achieved an IGF1 within reference range in 97% of patients. PegV has a half-life of O70 h suggesting weekly dosing may be possible but using higher doses than in the initial trials. Objective: To determine the efficacy of weekly dosing of pegV. Design: A two center, open-label prospective study in patients with acromegaly converted from a stable daily dose of pegV (median dose 15 mg daily (range 10-20 mg od), IGF1 normal for 3 months prior to inclusion) to twice-weekly (week 0-16) followed by once-weekly (week 16-32) administration. Results: Seven patients (4M, age 57G7 years, 6/7 prior transsphenoidal surgery, 7/7 prior radiotherapy) were recruited. Six patients completed the twice-weekly and five patients both the twice-weekly and once-weekly administration. Headaches led to two patient withdrawals at 0C24 weeks. Mean pre-dose serum IGF1 levels remained stable with the different administration regimens (IGF1 baseline 145G39 ng/ml, twice-weekly 124G39 ng/ml and once-weekly 127G22 ng/ml) and all values were within age adjusted IGF1 reference range. PegV dose was reduced in two patients and five opted to continue weekly administration at trial termination. Safety and quality of life parameters remained stable. Conclusions: Twice and once-weekly administration of pegV is effective in controlling serum IGF1 levels in acromegaly and although not formally assessed, continuation of weekly dosing in five patients at study conclusion suggests patient preference for this regimen.

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Gender, Body Weight, Disease Activity, and Previous Radiotherapy Influence the Response to Pegvisomant

Abstract: Sex, body weight, previous radiotherapy, and baseline GH/IGF-I influence the dose of pegvisomant required to normalize serum IGF-I in patients with active acromegaly.

Cited by 64 publications

References 37 publications

Therapy of acromegalic patients exacerbated by concomitant type 2 diabetes requires higher pegvisomant doses to normalise IGF1 levels

Therapy of acromegalic patients exacerbated by concomitant type 2 diabetes requires higher pegvisomant doses to normalise IGF1 levels

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

Successful use of weekly pegvisomant administration in patients with acromegaly

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