title: Long-term efficacy and safety of pegvisomant in combination with long-acting somatostatin analogs in acromegaly.
abstract: BACKGROUND
  Treatment for acromegaly patients with long-acting somatotropin release-inhibiting factor (LA-SRIF) often does not result in complete normalization of IGF-1. Addition of pegvisomant (PEGV), a GH receptor antagonist, could improve this; however, the literature has not described long-term follow-up.
  
  
  OBJECTIVE
  To assess long-term efficacy and safety of this combined treatment in the largest current single-center cohort of patients, from 2004-2013.
  
  
  METHODS
  Acromegaly patients were treated for at least 6 months with a high-dose LA-SRIF. To patients with persistently elevated IGF-1 levels (>1.2 × upper limit of normal) or poor quality of life, PEGV was added as one weekly injection.
  
  
  RESULTS
  The patients (n = 141) were treated with PEGV and LA-SRIFs for a median period of 4.9 years (range, 0.5-9.2). Efficacy, defined as the lowest measured IGF-1 level during treatment, was 97.0%. The median PEGV dose to achieve this efficacy was 80 mg weekly (interquartile range, 60-120 mg). Combination treatment-related adverse events were recorded in 26 subjects (18.4%). Pituitary tumor size increase was observed in one patient. Injection-site reactions were observed in four subjects. In 19 patients (13.5%), transiently elevated liver transaminases of more than three times the upper limit of normal were observed, of which 83% occurred within the first year of combination treatment. Eight patients died, at a mean age of 71 years; none of them were considered treatment-related.
  
  
  CONCLUSIONS
  The combination treatment with LA-SRIFs and PEGV was effective in 97% of the patients, it appears to be a safe medical treatment and it reduces the required dose of PEGV.
authors.affiliation: Department of Medicine, Endocrinology Section, Pituitary Center Rotterdam (S.J.C.M.M.N., S.E.F., R.A.F., J.A.M.J.L.J., L.J.H., A.J.v.d.L.), The Pituitary Center Rotterdam (S.J.C.M.M.N., A.H.G.D., R.M.L.P., R.A.F., J.A.M.J.L.J., L.J.H., A.J.v.d.L.), and Department of Medicine, Metabolism Section (F.W.M.d.R.), Erasmus University Medical Center Rotterdam, 3000 CA Rotterdam, The Netherlands; Department of Neurosurgery (M.B.), University Hospital Erlangen, 91054 Erlangen, Germany; and Medical Department (Endocrinology and Diabetes) (J.O.L.J.), Medical Research Laboratories, Clinical Institute, DK-8000 Aarhus C, Denmark.
authors.forename: S J C M M
authors.initials: SJ
authors.lastname: Neggers
authors.forename: S E
authors.initials: SE
authors.lastname: Franck
authors.forename: F W M
authors.initials: FW
authors.lastname: de Rooij
authors.forename: A H G
authors.initials: AH
authors.lastname: Dallenga
authors.forename: R M L
authors.initials: RM
authors.lastname: Poublon
authors.forename: R A
authors.initials: RA
authors.lastname: Feelders
authors.forename: J A M J L
authors.initials: JA
authors.lastname: Janssen
authors.forename: M
authors.initials: M
authors.lastname: Buchfelder
authors.forename: L J
authors.initials: LJ
authors.lastname: Hofland
authors.forename: J O L
authors.initials: JO
authors.lastname: Jørgensen
authors.forename: A J
authors.initials: AJ
authors.lastname: van der Lely
mesh_terms: D000172:Acromegaly / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics; D000328:Adult; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D014453:Glucuronosyltransferase / Q000235:genetics; D019382:Human Growth Hormone / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010911:Pituitary Neoplasms / Q000150:complications / Q000235:genetics / Q000473:pathology; D011986:Receptors, Somatotropin / Q000037:antagonists & inhibitors; D013004:Somatostatin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D062606:Tertiary Care Centers; D013995:Time; D016896:Treatment Outcome; D000099148:UGT1A1 Enzyme
chemical_list: D014453:Glucuronosyltransferase; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D011986:Receptors, Somatotropin; D013004:Somatostatin; D000099148:UGT1A1 Enzyme; C406545:pegvisomant