title: A multivariable prediction model for pegvisomant dosing: monotherapy and in combination with long-acting somatostatin analogues.
abstract: BACKGROUND
  Effective treatment of acromegaly with pegvisomant (PEGV), a growth hormone receptor antagonist, requires an appropriate dose titration. PEGV doses vary widely among individual patients, and various covariates may affect its dosing and pharmacokinetics.
  
  
  OBJECTIVE
  To identify predictors of the PEGV dose required to normalize insulin-like growth factor I (IGF-I) levels during PEGV monotherapy and in combination with long-acting somatostatin analogues (LA-SSAs).
  
  
  METHODS
  Two retrospective cohorts (Rotterdam + Liège Acromegaly Survey (LAS), totaln= 188) were meta-analyzed as a form of external replication to study the predictors of PEGV dosing in addition to LA-SSA, the LAS (n= 83) was used to study the predictors of PEGV monotherapy dosing. Multivariable regression models were used to identify predictors of the PEGV dose required to normalize IGF-I levels.
  
  
  RESULTS
  For PEGV dosing in combination with LA-SSA, IGF-I levels, weight, height and age, were associated with the PEGV normalization dosage (P≤ 0.001,P≤ 0.001,P= 0.028 andP= 0.047 respectively). Taken together, these characteristics predicted the PEGV normalization dose correctly in 63.3% of all patients within a range of ±60 mg/week (21.3% within a range of ±20 mg/week). For monotherapy, only weight was associated with the PEGV normalization dose (P≤ 0.001) and predicted this dosage correctly in 77.1% of all patients within a range of ±60 mg/week (31.3% within a range of ±20 mg/week).
  
  
  CONCLUSIONS
  In this study, we show that IGF-I levels, weight, height and age can contribute to define the optimal PEGV dose to normalize IGF-I levels in addition to LA-SSA. For PEGV monotherapy, only the patient's weight was associated with the IGF-I normalization PEGV dosage.
authors.affiliation: Department of Internal MedicineEndocrinology Section, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: S E
authors.initials: SE
authors.lastname: Franck
authors.affiliation: Department of Internal MedicineEndocrinology Section, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: T I M
authors.initials: TIM
authors.lastname: Korevaar
authors.affiliation: Department of Internal MedicineEndocrinology Section, Centre Hospitalier Universitaire de Liège, University of Liège, Domaine Universitaire du Sart-Tilman, Liège, Belgium.
authors.forename: P
authors.initials: P
authors.lastname: Petrossians
authors.affiliation: Department of Internal MedicineEndocrinology Section, Centre Hospitalier Universitaire de Liège, University of Liège, Domaine Universitaire du Sart-Tilman, Liège, Belgium.
authors.forename: A F
authors.initials: AF
authors.lastname: Daly
authors.affiliation: Assistance Publique-Hôpitaux de ParisHôpitaux Universitaires Paris-Sud, Hôpital de Bicêtre, Service d'Endocrinologie et des Maladies de la Reproduction, Le Kremlin Bicêtre, France.|Inserm 1185Fac Med Paris Sud, Univ Paris-Sud, Université Paris-Saclay, Le Kremlin-Bicêtre, France.
authors.forename: P
authors.initials: P
authors.lastname: Chanson
authors.affiliation: Department of Biotechnological and Applied Clinical SciencesUniversity of L'Aquila, L'Aquila and Neuromed, IRCCS, Pozzilli, Italy.
authors.forename: M L
authors.initials: ML
authors.lastname: Jaffrain-Réa
authors.affiliation: Aix-Marseille UniversitéCNRS, CRN2M UMR 7286, Marseille, France.|APHMHôpital Conception, Service d'Endocrinologie, Diabète et Maladies Métaboliques, Centre de Référence des Maladies Rares d'Origine Hypophysaire, Marseille, France.
authors.forename: T
authors.initials: T
authors.lastname: Brue
authors.affiliation: Clinical NeuroendocrinologyMax-Planck-Institute of Psychiatry, Munich, Germany.
authors.forename: G K
authors.initials: GK
authors.lastname: Stalla
authors.affiliation: Department of EndocrinologyDiabetes and Metabolism Section and Instituto de Investigação e Inovação em Saúde, University of Porto, Centro Hospitalar S. João , Porto, Portugal.
authors.forename: D
authors.initials: D
authors.lastname: Carvalho
authors.affiliation: Dipartimento di Medicina Clinica e ChirurgiaUniversità Federico II di Napoli, Naples, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Colao
authors.affiliation: 3rd Department of Internal MedicineFirst Medical Faculty, Charles University, Prague, Czech Republic.
authors.forename: V
authors.initials: V
authors.lastname: Hána
authors.affiliation: Department of EndocrinologyDiabetes, and Nutrition, University Hospital of Reims, Reims, France.
authors.forename: B
authors.initials: B
authors.lastname: Delemer
authors.affiliation: Servicio de EndocrinologíaHospital Universitario La Ribera, Valencia, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Fajardo
authors.affiliation: Department of Internal MedicineEndocrinology Section, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: A J
authors.initials: AJ
authors.lastname: van der Lely
authors.affiliation: Department of Internal MedicineEndocrinology Section, Centre Hospitalier Universitaire de Liège, University of Liège, Domaine Universitaire du Sart-Tilman, Liège, Belgium.
authors.forename: A
authors.initials: A
authors.lastname: Beckers
authors.affiliation: Department of Internal MedicineEndocrinology Section, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: S J C M M
authors.initials: SJCMM
authors.lastname: Neggers
mesh_terms: D000172:Acromegaly / Q000097:blood / Q000188:drug therapy*; D000328:Adult; D004359:Drug Therapy, Combination; D005260:Female; D019382:Human Growth Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D012189:Retrospective Studies; D013004:Somatostatin / Q000008:administration & dosage* / Q000031:analogs & derivatives*
chemical_list: D019382:Human Growth Hormone; D013004:Somatostatin; D007334:Insulin-Like Growth Factor I; C406545:pegvisomant