Long-term treatment with pegvisomant for acromegaly: a 10-year experience

Clin Endocrinol (Oxf). 2016 Apr;84(4):540-50. doi: 10.1111/cen.12993. Epub 2016 Jan 26.

Abstract

Background: Efficacy of the GH-receptor antagonist pegvisomant (PEG) has differed between preclinical and observational studies mainly due to dose adjustment and IGF-I normalization criteria. An escape phenomenon has also been described, but its definition and underlying causes have not been fully established.

Objective: To re-evaluate the outcomes of long-term PEG in a series of previously published patients and analyse the escape phenomenon.

Methods: We reviewed all patients with acromegaly resistant to SSA in whom PEG was started as monotherapy, who had been included in a previous publication. We prospectively evaluated 64 (56·3% women) from six tertiary care referral hospitals in Spain, for whom data as of June 2014 were available. Escape to PEG was defined as confirmed loss of biochemical control (IGF-I >1·2xULN), after at least 6 months of previous control with a stable dose of PEG.

Results: Patients were followed up for 13·0 (5·9-34·8) years since diagnosis, and 9·0 (4·1-10·4) years since the first administration of PEG. Fifty-one (89·5%) patients had an adequate IGF-I control at the last follow-up visit, 9 of them without treatment. Tumour growth was reported in 6 of 64 cases (9·4%), none of whom had received prior radiotherapy (P = 0·011). Seven patients died during follow-up. We found 16 escapes in 10 patients (15·6%). We identified potential underlying causes in 9 cases (tumour regrowth, previous treatment modifications, concomitant menopause and change in testosterone administration). The reason was unknown in 7 escapes, which occurred in 6 patients (9·4%). All patients, except one, achieved subsequent biochemical control after treatment adjustment.

Conclusions: We reassure the efficacy and safety of long-term PEG. An escape phenomenon may occur, but it can be overcome by adjusting therapy.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acromegaly / drug therapy*
  • Acromegaly / metabolism
  • Adult
  • Aged
  • Female
  • Follow-Up Studies
  • Human Growth Hormone / analogs & derivatives*
  • Human Growth Hormone / therapeutic use
  • Humans
  • Insulin-Like Growth Factor I / metabolism
  • Male
  • Middle Aged
  • Prospective Studies
  • Receptors, Somatotropin / antagonists & inhibitors
  • Receptors, Somatotropin / metabolism
  • Spain
  • Tertiary Care Centers
  • Time Factors
  • Treatment Outcome

Substances

  • Receptors, Somatotropin
  • Human Growth Hormone
  • Insulin-Like Growth Factor I
  • pegvisomant