Cesar L Boguszewski1, Martha Katherine P Huayllas2, Lucio Vilar3, Luciana Ansaneli Naves4, Antonio Ribeiro-Oliveira Junior5, Beatriz Santana Soares5, Mauro Antonio Czepielewski6, Julio Abucham7, Silvia Regina Correa-Silva7, Marcello Delano Bronstein8, Raquel Soares Jallad8, Felipe Gaia Duarte8, Nina Rosa Musolino9, Leandro Kasuki10, Monica Roberto Gadelha10,11. 1. Departamento de Medicina Interna, Serviço de Endocrinologia e Metabologia do Paraná (SEMPR), Hospital de Clínicas, Universidade Federal do Paraná (UFPR), Curitiba, PR, Brasil. 2. Departamento de Neuroendocrinologia, Hospital Brigadeiro, São Paulo, SP, Brasil. 3. Departamento de Endocrinologia, Hospital de Clínicas, Universidade Federal de Pernambuco (UFPE), Recife, PE, Brasil. 4. Faculdade de Ciências da Saúde, Universidade de Brasília (UnB), Brasília, DF, Brasil. 5. Laboratório de Endocrinologia, Departamento de Endocrinologia, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brasil. 6. Unidade de Endocrinologia, Hospital de Clínicas, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brasil. 7. Unidade de Neuroendocrinologia, Divisão de Endocrinologia e Metabolismo, Escola Paulista de Medicina, Universidade Federal de São Paulo (EPM-Unifesp), São Paulo, SP, Brasil. 8. Unidade Neuroendócrina, Divisão de Endocrinologia e Metabolismo, Hospital de Clínicas, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, SP, Brasil. 9. Divisão de Neurocirurgia Funcional, Instituto de Psiquiatria (IPq), Hospital de Clínicas, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, SP, Brasil. 10. Centro de Pesquisa em Neuroendocrinologia, Divisão de Endocrinologia, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro (HUCFF-UFRJ). 11. Divisão de Neuroendocrinologia, Instituto Estadual do Cérebro Paulo Niemeyer, Secretaria Estadual de Saúde, Rio de Janeiro, RJ, Brasil.
Abstract
OBJECTIVE: Investigate the therapeutic response of acromegaly patients to pegvisomant (PEGV) in a real-life, Brazilian multicenter study. SUBJECTS AND METHODS: Characteristics of acromegaly patients treated with PEGV were reviewed at diagnosis, just before and during treatment. All patients with at least two IGF-I measurements on PEGV were included. Efficacy was defined as any normal IGF-I measurement during treatment. Safety data were reviewed. Predictors of response were determined by comparing controlled versus uncontrolled patients. RESULTS: 109 patients [61 women; median age at diagnosis 34 years; 95.3% macroadenomas] from 10 Brazilian centers were studied. Previous treatment included surgery (89%), radiotherapy (34%), somatostatin receptor ligands (99%), and cabergoline (67%). Before PEGV, median levels of GH, IGF-I and IGF-I % of upper limit of normal were 4.3 µg/L, 613 ng/mL, and 209%, respectively. Pre-diabetes/diabetes was present in 48.6% and tumor remnant in 71% of patients. Initial dose was 10 mg/day in all except 4 cases, maximum dose was 30 mg/day, and median exposure time was 30.5 months. PEGV was used as monotherapy in 11% of cases. Normal IGF-I levels was obtained in 74.1% of patients. Glycemic control improved in 56.6% of patients with pre-diabetes/diabetes. Exposure time, pre-treatment GH and IGF-I levels were predictors of response. Tumor enlargement occurred in 6.5% and elevation of liver enzymes in 9.2%. PEGV was discontinued in 6 patients and 3 deaths unrelated to the drug were reported. CONCLUSIONS: In a real-life scenario, PEGV is a highly effective and safe treatment for acromegaly patients not controlled with other therapies.
OBJECTIVE: Investigate the therapeutic response of acromegalypatients to pegvisomant (PEGV) in a real-life, Brazilian multicenter study. SUBJECTS AND METHODS: Characteristics of acromegalypatients treated with PEGV were reviewed at diagnosis, just before and during treatment. All patients with at least two IGF-I measurements on PEGV were included. Efficacy was defined as any normal IGF-I measurement during treatment. Safety data were reviewed. Predictors of response were determined by comparing controlled versus uncontrolled patients. RESULTS: 109 patients [61 women; median age at diagnosis 34 years; 95.3% macroadenomas] from 10 Brazilian centers were studied. Previous treatment included surgery (89%), radiotherapy (34%), somatostatin receptor ligands (99%), and cabergoline (67%). Before PEGV, median levels of GH, IGF-I and IGF-I % of upper limit of normal were 4.3 µg/L, 613 ng/mL, and 209%, respectively. Pre-diabetes/diabetes was present in 48.6% and tumor remnant in 71% of patients. Initial dose was 10 mg/day in all except 4 cases, maximum dose was 30 mg/day, and median exposure time was 30.5 months. PEGV was used as monotherapy in 11% of cases. Normal IGF-I levels was obtained in 74.1% of patients. Glycemic control improved in 56.6% of patients with pre-diabetes/diabetes. Exposure time, pre-treatment GH and IGF-I levels were predictors of response. Tumor enlargement occurred in 6.5% and elevation of liver enzymes in 9.2%. PEGV was discontinued in 6 patients and 3 deaths unrelated to the drug were reported. CONCLUSIONS: In a real-life scenario, PEGV is a highly effective and safe treatment for acromegalypatients not controlled with other therapies.
Authors: Andrea Giustina; Garni Barkhoudarian; Albert Beckers; Anat Ben-Shlomo; Nienke Biermasz; Beverly Biller; Cesar Boguszewski; Marek Bolanowski; Jens Bollerslev; Vivien Bonert; Marcello D Bronstein; Michael Buchfelder; Felipe Casanueva; Philippe Chanson; David Clemmons; Maria Fleseriu; Anna Maria Formenti; Pamela Freda; Monica Gadelha; Eliza Geer; Mark Gurnell; Anthony P Heaney; Ken K Y Ho; Adriana G Ioachimescu; Steven Lamberts; Edward Laws; Marco Losa; Pietro Maffei; Adam Mamelak; Moises Mercado; Mark Molitch; Pietro Mortini; Alberto M Pereira; Stephan Petersenn; Kalmon Post; Manuel Puig-Domingo; Roberto Salvatori; Susan L Samson; Ilan Shimon; Christian Strasburger; Brooke Swearingen; Peter Trainer; Mary L Vance; John Wass; Margaret E Wierman; Kevin C J Yuen; Maria Chiara Zatelli; Shlomo Melmed Journal: Rev Endocr Metab Disord Date: 2020-09-10 Impact factor: 6.514
Authors: Maria Fleseriu; Beverly M K Biller; Pamela U Freda; Monica R Gadelha; Andrea Giustina; Laurence Katznelson; Mark E Molitch; Susan L Samson; Christian J Strasburger; A J van der Lely; Shlomo Melmed Journal: Pituitary Date: 2020-10-20 Impact factor: 4.107
Authors: Maria Fleseriu; Dagmar Führer-Sakel; Aart J van der Lely; Laura De Marinis; Thierry Brue; Joli van der Lans-Bussemaker; Judith Hey-Hadavi; Cecilia Camacho-Hubner; Michael P Wajnrajch; Srinivas Rao Valluri; Andrew Anthony Palladino; Roy Gomez; Roberto Salvatori Journal: Eur J Endocrinol Date: 2021-08-27 Impact factor: 6.664