Pegvisomant in acromegaly: an update

Abstract

BackgroundIn 2007, we published an opinion document to review the role of pegvisomant (PEG) in the treatment of acromegaly. Since then, new evidence emerged on the biochemical and clinical effects of PEG and on its long-term efficacy and safety.AimWe here reviewed the emerging aspects of the use of PEG in clinical practice in the light of the most recent literature.ResultsThe clinical use of PEG is still suboptimal, considering that it remains the most powerful tool to control IGF-I in acromegaly allowing to obtain, with a pharmacological treatment, the most important clinical effects in terms of signs and symptoms, quality of life and comorbidities. The number of patients with acromegaly exposed to PEG worldwide has become quite elevated and the prolonged follow-up allows now to deal quite satisfactorily with many clinical issues including major safety issues, such as the concerns about possible tumour (re)growth under PEG. The positive or neutral impact of PEG on glucose metabolism has been highlighted, and the clinical experience, although limited, with sleep apnoea and pregnancy has been reviewed. Finally, the current concept of somatostatin receptor ligands (SRL) resistance has been addressed, in order to better define the acromegaly patients to whom the PEG option may be offered.ConclusionsPEG increasingly appears to be an effective and safe medical option for many patients not controlled by SRL but its use still needs to be optimized.

A Consensus Statement on acromegaly therapeutic outcomes

“…The SRLs octreotide, lanreotide and pasireotide, as well as the dopamine agonist cabergoline, bind cognate receptors in the adenoma and suppress GH secretion; the GH antagonist pegvisomant blocks GH action in the periphery and blocks generation of IGF1 (refs [57][58][59] ).…”

“…Pegvisomant is approved for use at doses ranging from 10 mg per day to 30 mg per day, and we recommend that the daily dose should be increased to the recommended highest dose as needed (SR). Patient-specific factors such as age and BMI have been identified as predictive of the dose of pegvisomant that is required for normalization of IGF1 levels 78,79 (LQ), but we recommend that physicians should regularly monitor IGF1 levels throughout therapy to determine whether normalization can be achieved by adapting the dose regimen 59 (SR). Surveillance studies show that high doses of up to 60 mg per day have been used in patients with persistently elevated IGF1 levels 80 ; however, use of doses above 30 mg per day is not approved, has not been prospectively studied and therefore is not recommended in clinical practice (DR).…”

Brazilian multicenter study on pegvisomant treatment in acromegaly

“…Despite that many patients obtain biochemical control of the disease with surgery, radiotherapy and/or medical therapy with somatostatin receptor ligands (SRL) and/ or cabergoline, a significant proportion of acromegaly patients remain inadequately controlled and in need of additional treatment (5). Accordingly, PEGV was approved in Europe, USA and other countries around the world for the treatment of acromegaly in patients previously treated by surgery or radiotherapy and not controlled with maximum doses of SRLs (4,6). In these cases, PEGV may be used as monotherapy or in combination therapy with SRL and/or cabergoline.…”

Manajemen Anestesi pada Pasien dengan Akromegali yang Menjalani Prosedur Reseksi Tumor Adenohipofise melalui Pendekatan Sublabial Transphenoidal

“…Tujuan dari terapi biokimia dari akromegali adalah untuk mengembalikan aksis GH/IGF-1 ke dalam batas normal. 17 Pada fasilitas yang memiliki pemeriksaan lab yang lengkap sebaiknya pemeriksaan IGF-1 dilakukan oleh karena peningkatan sekresi dari GH menyebabkan peningkatan produksi IGF-1. 18 Berdasarkan bukti terbaru, kadar GH kurang dari 2-2.5 mug/L adalah prediktor yang lebih baik dibandingkan kadar IGF-1 yang normal, hal ini kemungkinan disebabkan oleh perbedaan antara GH and IGF-1 pada kadar GH yang rendah.…”

“…Dengan agen ini, kadar GH dalam sirkulasi meningkat sebagai pengaruh dari penurunan kadar IGF-I. 17 Komplikasi Resiko tindakan anestesi pada kasus akromegali meliputi kesulitan pada penanganan jalan nafas, hipertensi, masalah di jantung, ginjal, diabetes dan sistem endokrin. 10 Akromegali adalah penyakit serius yang dapat meningkatkan angka kesakitan dan kematian.…”