title: Long-term treatment with pegvisomant for acromegaly: a 10-year experience.
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.
authors.affiliation: Department of Endocrinology, Hospital Universitario de la Princesa, Instituto de Investigación Princesa, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Ramos-Leví
authors.affiliation: Department of Endocrinology, Complejo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Bernabeu
authors.affiliation: Department of Endocrinology, Hospital La Paz, Instituto de Investigación La Paz, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Álvarez-Escolá
authors.affiliation: Department of Endocrinology, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Aller
authors.affiliation: Department of Endocrinology, HM Hospital Universitario San Chinarro, Madrid, Spain.
authors.forename: Tomás
authors.initials: T
authors.lastname: Lucas
authors.affiliation: Department of Endocrinology, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria San Carlos, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: Paz
authors.initials: P
authors.lastname: de Miguel
authors.affiliation: Department of Endocrinology, Complejo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: Leticia
authors.initials: L
authors.lastname: Rodríguez-Cañete
authors.affiliation: Department of Endocrinology, Hospital Universitario de la Princesa, Instituto de Investigación Princesa, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Sampedro-Núñez
authors.affiliation: Department of Endocrinology, Hospital Clinic, Barcelona, Spain.
authors.forename: Irene
authors.initials: I
authors.lastname: Halperin
authors.affiliation: Department of Endocrinology, Hospital German Trias i Pujol. Instituto de Investigación German Trias I Pujol, Barcelona, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Puig-Domingo
authors.affiliation: Department of Endocrinology, Hospital Universitario de la Princesa, Instituto de Investigación Princesa, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Mónica
authors.initials: M
authors.lastname: Marazuela
mesh_terms: D000172:Acromegaly / Q000188:drug therapy* / Q000378:metabolism; D000328:Adult; D000368:Aged; D005260:Female; D005500:Follow-Up Studies; D019382:Human Growth Hormone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011986:Receptors, Somatotropin / Q000037:antagonists & inhibitors / Q000378:metabolism; D013030:Spain; D062606:Tertiary Care Centers; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D011986:Receptors, Somatotropin; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; C406545:pegvisomant