Pegvisomant

Pegvisomant is an analog of human GH, acts as a competitive inhibitor of the GH receptor.

Indications

Second or third-line therapy to control the metabolic effects of acromegaly in patients who did not achieve a biochemical remission after surgery and/or radiation therapy. Can be used alone or in combination with SRLs and/or cabergoline.

Effectiveness

IGF-1 normalization in ~ 60% of patients.

Dose

Loading dose 40 mg subq once. Starting 10 mg/day. Max 30 mg/day.

Monitoring and Adjustment

• Increase dose by 5 mg/day every 1-2 months until IGF-1 is normalized.
• Since pegvisomant acts at the level of the GH receptor, GH levels are not a useful marker of response to therapy. GH levels are typically increased, but IGF-1 levels and symptoms are reduced.
• Monitor liver enzymes q 1 month x 6 months then q 3 months x 6 months then q 6 months.

Adverse Reactions

• Tumour volume increase (Nelson syndrome) ~ 3.2%. More likely to occur in patients who were not treated with radiation therapy and who were switched from SRL to pegvisomant.
• Injection-site reactions ~ 2%.
• Elevated AST or ALT ≥ 3x ULN ~ 2.5%.

References

• Buhk JH, Jung S, Psychogios MN, Göricke S, Hartz S, Schulz-Heise S, Klingebiel R, Forsting M, Brückmann H, Dörfler A, Jordan M, Buchfelder M, Knauth M. Tumor volume of growth hormone-secreting pituitary adenomas during treatment with pegvisomant: a prospective multicenter study. JCEM. 2010 Feb;95(2):552-8.
• van der Lely AJ, Biller BM, Brue T, Buchfelder M, Ghigo E, Gomez R, Hey-Hadavi J, Lundgren F, Rajicic N, Strasburger CJ, Webb SM, Koltowska-Häggström M. Long-term safety of pegvisomant in patients with acromegaly: comprehensive review of 1288 subjects in ACROSTUDY. JCEM. 2012 May;97(5):1589-97.