title: Escape and lipodystrophy in acromegaly during pegvisomant therapy, a retrospective multicentre Spanish study.
abstract: BACKGROUND
  Pegvisomant is an effective treatment for acromegaly.
  
  
  OBJECTIVE
  To investigate escape (loss of biochemical control in patients previously controlled) and lipodystrophy in acromegalic patients treated with pegvisomant and to evaluate possible associations with clinical features.
  
  
  METHODS
  Multicentre retrospective study involving 19 Spanish centres.
  
  
  RESULTS
  Ninety-seven patients were included (59% women, mean age at diagnosis 42 ± 13 years, 80% macroadenomas); mean follow-up on pegvisomant was 5 ± 2·5 years, and 89 (92%) achieved normal IGF-1. Escape was reported in 30/89 (34%) of responders, after a mean treatment duration of 25 ± 21 months. The mean initial dose of pegvisomant was 11 ± 5 mg/day, and mean dose at escape was 14 ± 7 mg/day. Most patients (26/30, 87%) achieved control with dose increase (57%), additional medical treatment (3%) or both (27%). Mean new dose that controlled IGF-1 after escape was 20 ± 7 mg/day. Treatments associated were somatostatin analogues (SSA in 47%), cabergoline (CAB in 47%) and both (6%). Lipodystrophy was observed in 15 patients (13 females), mild in six, moderate in six, severe in three and persistent in four. Among patients with lipodystrophy, three escaped and three were nonresponders to pegvisomant. Four patients discontinued the drug, and four had dose reductions because of lipodystrophy. It tended to be more frequent in females (P = 0·06) and in patients treated with triple association SSA+CAB+PEG (P = 0·018). No relationship between escape and clinical variables was found, except prior CAB (P = 0·04) and metformin treatment (0·02) and grade of lipodystrophy (P = 0·02).
  
  
  CONCLUSIONS
  A significant proportion of patients treated with pegvisomant escaped (34%); however, the majority (87%) was easily controlled with either dose increase, further medical treatment or both. Lipodystrophy developed in 15%, mostly females, and influenced the response to treatment.
authors.affiliation: Servicio Endocrinología, Hospital Quirón- Dexeus, Barcelona, Spain.
authors.forename: Gemma
authors.initials: G
authors.lastname: Sesmilo
authors.forename: Eugenia
authors.initials: E
authors.lastname: Resmini
authors.forename: Ignacio
authors.initials: I
authors.lastname: Bernabeu
authors.forename: Javier
authors.initials: J
authors.lastname: Aller
authors.forename: Alfonso
authors.initials: A
authors.lastname: Soto
authors.forename: Mireia
authors.initials: M
authors.lastname: Mora
authors.forename: Antonio
authors.initials: A
authors.lastname: Picó
authors.forename: Carmen
authors.initials: C
authors.lastname: Fajardo
authors.forename: Elena
authors.initials: E
authors.lastname: Torres
authors.forename: Cristina
authors.initials: C
authors.lastname: Alvarez-Escolá
authors.forename: Rogelio
authors.initials: R
authors.lastname: García
authors.forename: Concepción
authors.initials: C
authors.lastname: Blanco
authors.forename: Rosa
authors.initials: R
authors.lastname: Cámara
authors.forename: Sonia
authors.initials: S
authors.lastname: Gaztambide
authors.forename: Isabel
authors.initials: I
authors.lastname: Salinas
authors.forename: Carlos Del
authors.initials: CD
authors.lastname: Pozo
authors.forename: Ignasi
authors.initials: I
authors.lastname: Castells
authors.forename: Carles
authors.initials: C
authors.lastname: Villabona
authors.forename: Betina
authors.initials: B
authors.lastname: Biagetti
authors.forename: Susan M
authors.initials: SM
authors.lastname: Webb
mesh_terms: D000236:Adenoma / Q000188:drug therapy* / Q000378:metabolism; D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000077465:Cabergoline; D004359:Drug Therapy, Combination; D004873:Ergolines / Q000627:therapeutic use; D005260:Female; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000188:drug therapy* / Q000378:metabolism; D019382:Human Growth Hormone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D007279:Injections, Subcutaneous; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008060:Lipodystrophy / Q000139:chemically induced*; D008297:Male; D008875:Middle Aged; D015282:Octreotide / Q000627:therapeutic use; D011986:Receptors, Somatotropin / Q000037:antagonists & inhibitors*; D012189:Retrospective Studies; D013030:Spain; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D004873:Ergolines; D011986:Receptors, Somatotropin; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D000077465:Cabergoline; C406545:pegvisomant; D015282:Octreotide