M Ragonese1, S Grottoli2, P Maffei3, A Alibrandi4, M R Ambrosio5, G Arnaldi6, A Bianchi7, S Puglisi1, M C Zatelli5, L De Marinis7, E Ghigo2, A Giustina8, F Maffezzoni8, C Martini3, L Trementino6, S Cannavo9. 1. Dipartimento di Patologia Umana dell'adulto e dell'età evolutiva "G. Barresi", AOU Policlinico G. Martino, University of Messina, Via Consolare Valeria, 1, 98125, Messina, Italy. 2. Divisione di Endocrinologia, Diabetologia E Metabolismo, Dipartimento di Scienze Mediche, AO Città Della Salute E Della Scienza di Torino, Università di Torino, Turin, Italy. 3. Dipartimento di Medicina, AO di Padova, Padua, Italy. 4. Dipartimento di Economia, Sezione di Scienze Statistiche E Matematiche, Università di Messina, Messina, Italy. 5. Dipartimento di Scienze Mediche, Sezione di Endocrinologia E Medicina Interna, Università di Ferrara, Ferrara, Italy. 6. SOD Clinica di Endocrinologia E Malattie Del Metabolismo, AOU Ospedali Riuniti di Ancona, Università di Ancona, Torrette, Ancona, Italy. 7. UOS Patologia Ipofisaria, Istituto di Patologia Medica, Policlinico Universitario A. Gemelli, Rome, Italy. 8. Struttura Ambulatoriale di Endocrinologia, AO Spedali Civili di Brescia, Università di Brescia, Brescia, Italy. 9. Dipartimento di Patologia Umana dell'adulto e dell'età evolutiva "G. Barresi", AOU Policlinico G. Martino, University of Messina, Via Consolare Valeria, 1, 98125, Messina, Italy. cannavos@unime.it.
Abstract
PURPOSE: Pegvisomant (PEGV) treatment in acromegaly patients resistant to somatostatin analogues is less effective in the real life than in clinical trials. This is a multicenter, observational, retrospective, longitudinal study. The aim was to detect characteristics which improve long-term PEGV effectiveness. METHODS: 87 acromegalic patients treated with PEGV have been enrolled in seven referral Italian centres. PEGV was administered for up to 4 years, at doses up titrated until IGF-1 normalization or to ≥ 30 mg/day. The rate of patients who reached IGF-1 normalization at last visit has been calculated. RESULTS: IGF-1 was normalized in 75.9% of patients after 1 year and in 89.6% at last visit. Disease control was associated with lower baseline GH, IGF-1 and IGF-1 xULN and was more frequent when baseline IGF-1 was < 2.7 × ULN (p < 0.02). PEGV dose was dependent on baseline IGF-1 > 2.7 × ULN (p < 0.05) and doses > 1.0 mg/BMI/day were administered more frequently when baseline IGF-1 was > 2.0 × ULN (p = 0.03). PEGV resistance was associated with higher BMI (p = 0.006) and was more frequent when BMI was > 30 kg/m2 (p = 0.07). There were no significant differences between patients treated with monotherapy or combined treatment. IGF-1 normalization, PEGV dose and rate of associated treatment were similar between males and females. PEGV effectiveness was independent from previous management. Diabetic patients needed higher doses of PEGV than non-diabetic ones. CONCLUSIONS: PEGV effectiveness improves when up titration is appropriate. Higher PEGV doses at start and a more rapid up-titration are necessary in patients with obesity and/or IGF-1 > 2.7 × ULN.
PURPOSE:Pegvisomant (PEGV) treatment in acromegalypatients resistant to somatostatin analogues is less effective in the real life than in clinical trials. This is a multicenter, observational, retrospective, longitudinal study. The aim was to detect characteristics which improve long-term PEGV effectiveness. METHODS: 87 acromegalicpatients treated with PEGV have been enrolled in seven referral Italian centres. PEGV was administered for up to 4 years, at doses up titrated until IGF-1 normalization or to ≥ 30 mg/day. The rate of patients who reached IGF-1 normalization at last visit has been calculated. RESULTS:IGF-1 was normalized in 75.9% of patients after 1 year and in 89.6% at last visit. Disease control was associated with lower baseline GH, IGF-1 and IGF-1 xULN and was more frequent when baseline IGF-1 was < 2.7 × ULN (p < 0.02). PEGV dose was dependent on baseline IGF-1 > 2.7 × ULN (p < 0.05) and doses > 1.0 mg/BMI/day were administered more frequently when baseline IGF-1 was > 2.0 × ULN (p = 0.03). PEGV resistance was associated with higher BMI (p = 0.006) and was more frequent when BMI was > 30 kg/m2 (p = 0.07). There were no significant differences between patients treated with monotherapy or combined treatment. IGF-1 normalization, PEGV dose and rate of associated treatment were similar between males and females. PEGV effectiveness was independent from previous management. Diabeticpatients needed higher doses of PEGV than non-diabetic ones. CONCLUSIONS:PEGV effectiveness improves when up titration is appropriate. Higher PEGV doses at start and a more rapid up-titration are necessary in patients with obesity and/or IGF-1 > 2.7 × ULN.
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